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Conserved domains on  [gi|31455611|ref|NP_001070|]
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tyrosine-protein kinase ZAP-70 isoform 1 [Homo sapiens]

Protein Classification

tyrosine-protein kinase ZAP-70( domain architecture ID 10177821)

tyrosine-protein kinase ZAP-70 (70 kDa zeta-chain associated protein) is a cytoplasmic (or nonreceptor) kinase containing two Src homology 2 (SH2) domains N-terminal to a tyr kinase domain that catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
333-601 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 584.99  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 333 KRDNLLIADIELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALML 412
Cdd:cd05115   1 KRDNLLIDEVELGSGNFGCVKKGVYKMRKKQIDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVCEAEALML 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 413 VMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSY 492
Cdd:cd05115  81 VMEMASGGPLNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGADDSY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALM 572
Cdd:cd05115 161 YKARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALM 240
                       250       260
                ....*....|....*....|....*....
gi 31455611 573 SDCWIYKWEDRPDFLTVEQRMRACYYSLA 601
Cdd:cd05115 241 SDCWIYKWEDRPNFLTVEQRMRTYYYSIA 269
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
152-255 3.57e-72

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198265  Cd Length: 105  Bit Score: 227.11  E-value: 3.57e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 152 LIATTAHERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDT 231
Cdd:cd10402   1 LIATTAHERMPWYHGSIARDEAERRLYSGAQPDGKFLLRERKESGTYALSLVYGKTVYHYRIDQDKSGKYSIPEGTKFDT 80
                        90       100
                ....*....|....*....|....
gi 31455611 232 LWQLVEYLKLKADGLIYCLKEACP 255
Cdd:cd10402  81 LWQLVEYLKLKPDGLIFVLRESCP 104
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
8-111 1.12e-67

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198191  Cd Length: 104  Bit Score: 215.34  E-value: 1.12e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   8 LPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFY 87
Cdd:cd09938   1 LPFFYGSITREEAEEYLKLAGMSDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIERQLNGTYAIAGGKAHCGPAELCEYH 80
                        90       100
                ....*....|....*....|....
gi 31455611  88 SRDPDGLPCNLRKPCNRPSGLEPQ 111
Cdd:cd09938  81 STDLDGLVCLLRKPCNRPPGVEPK 104
 
Name Accession Description Interval E-value
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
333-601 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 584.99  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 333 KRDNLLIADIELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALML 412
Cdd:cd05115   1 KRDNLLIDEVELGSGNFGCVKKGVYKMRKKQIDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVCEAEALML 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 413 VMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSY 492
Cdd:cd05115  81 VMEMASGGPLNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGADDSY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALM 572
Cdd:cd05115 161 YKARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALM 240
                       250       260
                ....*....|....*....|....*....
gi 31455611 573 SDCWIYKWEDRPDFLTVEQRMRACYYSLA 601
Cdd:cd05115 241 SDCWIYKWEDRPNFLTVEQRMRTYYYSIA 269
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
343-593 6.38e-123

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 363.74  E-value: 6.38e-123
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   343 ELGCGNFGSVRQGVYRMRKKQ--IDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:pfam07714   6 KLGEGAFGEVYKGTLKGEGENtkIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCtQGEPLYIVTEYMPG 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGaDDSYYTARSAG 499
Cdd:pfam07714  86 GDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIY-DDDYYRKRGGG 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:pfam07714 165 KLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYD 244
                         250
                  ....*....|....
gi 31455611   580 WEDRPDFLTVEQRM 593
Cdd:pfam07714 245 PEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
343-593 1.12e-121

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 360.69  E-value: 1.12e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    343 ELGCGNFGSVRQGVYRMR--KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:smart00219   6 KLGEGAFGEVYKGKLKGKggKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCtEEEPLYIVMEYMEG 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGaDDSYYTARSaG 499
Cdd:smart00219  86 GDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLY-DDDYYRKRG-G 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:smart00219 164 KLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAED 243
                          250
                   ....*....|....
gi 31455611    580 WEDRPDFLTVEQRM 593
Cdd:smart00219 244 PEDRPTFSELVEIL 257
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
152-255 3.57e-72

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 227.11  E-value: 3.57e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 152 LIATTAHERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDT 231
Cdd:cd10402   1 LIATTAHERMPWYHGSIARDEAERRLYSGAQPDGKFLLRERKESGTYALSLVYGKTVYHYRIDQDKSGKYSIPEGTKFDT 80
                        90       100
                ....*....|....*....|....
gi 31455611 232 LWQLVEYLKLKADGLIYCLKEACP 255
Cdd:cd10402  81 LWQLVEYLKLKPDGLIFVLRESCP 104
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
8-111 1.12e-67

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 215.34  E-value: 1.12e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   8 LPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFY 87
Cdd:cd09938   1 LPFFYGSITREEAEEYLKLAGMSDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIERQLNGTYAIAGGKAHCGPAELCEYH 80
                        90       100
                ....*....|....*....|....
gi 31455611  88 SRDPDGLPCNLRKPCNRPSGLEPQ 111
Cdd:cd09938  81 STDLDGLVCLLRKPCNRPPGVEPK 104
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
343-571 6.11e-35

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 138.22  E-value: 6.11e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKVLKQgtEKADTEEMM----REAQIMHQLDNPYIVRLIGVCQAEALM-LVME 415
Cdd:COG0515  14 LLGRGGMGVV----YLARDLRLGrpVALKVLRP--ELAADPEARerfrREARALARLNHPNIVRVYDVGEEDGRPyLVME 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:COG0515  88 YVEGESLAD-LLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTG 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWPlkwY-APECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRM---ECPPECPPELYAL 571
Cdd:COG0515 167 TVVGTPG---YmAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPppsELRPDLPPALDAI 242
SH2 pfam00017
SH2 domain;
10-87 1.57e-25

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 99.98  E-value: 1.57e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611    10 FFYGSISRAEAEEHLkLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFY 87
Cdd:pfam00017   1 WYHGKISRQEAERLL-LNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGGYYISGGVKFSSLAELVEHY 77
SH2 pfam00017
SH2 domain;
163-238 1.92e-25

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 99.98  E-value: 1.92e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611   163 WYHSSLTREEAERKLYSGaQTDGKFLLRPR-KEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEY 238
Cdd:pfam00017   1 WYHGKISRQEAERLLLNG-KPDGTFLVRESeSTPGGYTLSVRDDGKVKHYKIQSTDNGGYYISGGVKFSSLAELVEH 76
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
161-245 1.19e-23

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 94.99  E-value: 1.19e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    161 MPWYHSSLTREEAERKLYSGAqtDGKFLLRP-RKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYL 239
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG--DGDFLVRDsESSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHY 78

                   ....*.
gi 31455611    240 KLKADG 245
Cdd:smart00252  79 QKNSLG 84
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
9-93 3.80e-21

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 87.67  E-value: 3.80e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611      9 PFFYGSISRAEAEEHLKlaGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFYS 88
Cdd:smart00252   2 PWYHGFISREEAEKLLK--NEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHYQ 79

                   ....*
gi 31455611     89 RDPDG 93
Cdd:smart00252  80 KNSLG 84
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
325-540 2.09e-16

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 80.63  E-value: 2.09e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  325 LKDKKLFLKRD--NLLIADIE----LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNP 396
Cdd:PTZ00263   1 MKAAYMFTKPDtsSWKLSDFEmgetLGTGSFGRVR--IAKHKGTGEYYAIKCLKKREilKMKQVQHVAQEKSILMELSHP 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  397 YIVRLI-GVCQAEALMLVMEMAGGGPLHKFLvGKREEIPvSNVAELLH-QVSMGMKYLEEKNFVHRDLAARNVLLVNRHY 474
Cdd:PTZ00263  79 FIVNMMcSFQDENRVYFLLEFVVGGELFTHL-RKAGRFP-NDVAKFYHaELVLAFEYLHSKDIIYRDLKPENLLLDNKGH 156
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611  475 AKISDFGLSKALgaDDSYYTARSAgkwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:PTZ00263 157 VKVTDFGFAKKV--PDRTFTLCGT---P-EYLAPEVIQSKGHGKAVDWWTMGVLLYEFIA-GYPPF 215
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
365-540 1.32e-11

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 67.51  E-value: 1.32e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  365 DVAIKVLKqgTEKADTEEMM----REAQIMHQLDNPYIVRLIGVCQAEAL-MLVMEMAGGGPLHKFLvgkREE--IPVSN 437
Cdd:NF033483  34 DVAVKVLR--PDLARDPEFVarfrREAQSAASLSHPNIVSVYDVGEDGGIpYIVMEYVDGRTLKDYI---REHgpLSPEE 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  438 VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTAR---SAGkwplkwY-APECINF 513
Cdd:NF033483 109 AVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSTTMTQTNSvlgTVH------YlSPEQARG 182
                        170       180
                 ....*....|....*....|....*..
gi 31455611  514 RKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:NF033483 183 GTVDARSDIYSLGIVLYEMLT-GRPPF 208
 
Name Accession Description Interval E-value
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
333-601 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 584.99  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 333 KRDNLLIADIELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALML 412
Cdd:cd05115   1 KRDNLLIDEVELGSGNFGCVKKGVYKMRKKQIDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVCEAEALML 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 413 VMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSY 492
Cdd:cd05115  81 VMEMASGGPLNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGADDSY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALM 572
Cdd:cd05115 161 YKARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALM 240
                       250       260
                ....*....|....*....|....*....
gi 31455611 573 SDCWIYKWEDRPDFLTVEQRMRACYYSLA 601
Cdd:cd05115 241 SDCWIYKWEDRPNFLTVEQRMRTYYYSIA 269
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
342-598 1.78e-174

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 495.33  E-value: 1.78e-174
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGVYRMRK-KQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGG 420
Cdd:cd05060   1 KELGHGNFGSVRKGVYLMKSgKEVEVAVKTLKQEHEKAGKKEFLREASVMAQLDHPCIVRLIGVCKGEPLMLVMELAPLG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGK 500
Cdd:cd05060  81 PLLKYLKKRRE-IPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALGAGSDYYRATTAGR 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd05060 160 WPLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRP 239
                       250
                ....*....|....*...
gi 31455611 581 EDRPDFLTVEQRMRACYY 598
Cdd:cd05060 240 EDRPTFSELESTFRRDPE 257
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
343-598 2.70e-147

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 426.30  E-value: 2.70e-147
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLK-QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGP 421
Cdd:cd05116   2 ELGSGNFGTVKKGYYQMKKVVKTVAVKILKnEANDPALKDELLREANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKW 501
Cdd:cd05116  82 LNKFL-QKNRHVTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKW 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05116 161 PVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYDVD 240
                       250
                ....*....|....*..
gi 31455611 582 DRPDFLTVEQRMRACYY 598
Cdd:cd05116 241 ERPGFAAVELRLRNYYY 257
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
343-593 6.38e-123

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 363.74  E-value: 6.38e-123
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   343 ELGCGNFGSVRQGVYRMRKKQ--IDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:pfam07714   6 KLGEGAFGEVYKGTLKGEGENtkIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCtQGEPLYIVTEYMPG 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGaDDSYYTARSAG 499
Cdd:pfam07714  86 GDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIY-DDDYYRKRGGG 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:pfam07714 165 KLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYD 244
                         250
                  ....*....|....
gi 31455611   580 WEDRPDFLTVEQRM 593
Cdd:pfam07714 245 PEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
343-593 1.12e-121

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 360.69  E-value: 1.12e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    343 ELGCGNFGSVRQGVYRMR--KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:smart00219   6 KLGEGAFGEVYKGKLKGKggKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCtEEEPLYIVMEYMEG 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGaDDSYYTARSaG 499
Cdd:smart00219  86 GDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLY-DDDYYRKRG-G 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:smart00219 164 KLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAED 243
                          250
                   ....*....|....
gi 31455611    580 WEDRPDFLTVEQRM 593
Cdd:smart00219 244 PEDRPTFSELVEIL 257
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
338-593 1.46e-120

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 358.01  E-value: 1.46e-120
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    338 LIADIELGCGNFGSVRQGVYRMRK--KQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVM 414
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGKGdgKEVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCtEEEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    415 EMAGGGPLHKFLVGKRE-EIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGaDDSYY 493
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPkELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLY-DDDYY 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    494 TARSaGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMS 573
Cdd:smart00221 160 KVKG-GKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLML 238
                          250       260
                   ....*....|....*....|
gi 31455611    574 DCWIYKWEDRPDFLTVEQRM 593
Cdd:smart00221 239 QCWAEDPEDRPTFSELVEIL 258
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
343-594 1.98e-109

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 329.50  E-value: 1.98e-109
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQ-IDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGG 420
Cdd:cd00192   2 KLGEGAFGEVYKGKLKGGDGKtVDVAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCtEEEPLYLVMEYMEGG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEIPVSN-----VAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKaLGADDSY 492
Cdd:cd00192  82 DLLDFLRKSRPVFPSPEpstlsLKDLLSfaiQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSR-DIYDDDY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALM 572
Cdd:cd00192 161 YRKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYELM 240
                       250       260
                ....*....|....*....|..
gi 31455611 573 SDCWIYKWEDRPDFLTVEQRMR 594
Cdd:cd00192 241 LSCWQLDPEDRPTFSELVERLE 262
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
332-586 1.77e-89

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 278.54  E-value: 1.77e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 332 LKRDNLLIADIeLGCGNFGSVRQGVYRMRK-KQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEAL 410
Cdd:cd05056   3 IQREDITLGRC-IGEGQFGDVYQGVYMSPEnEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITENPV 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 411 MLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADD 490
Cdd:cd05056  82 WIVMELAPLGELRSYLQVNKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYM-EDE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTArSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYA 570
Cdd:cd05056 161 SYYKA-SKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYS 239
                       250
                ....*....|....*.
gi 31455611 571 LMSDCWIYKWEDRPDF 586
Cdd:cd05056 240 LMTKCWAYDPSKRPRF 255
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
343-586 9.60e-84

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 263.05  E-value: 9.60e-84
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRK-KQIDVAIKVLKQG--TEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGG 419
Cdd:cd05040   2 KLGDGSFGVVRRGEWTTPSgKVIQVAVKCLKSDvlSQPNAMDDFLKEVNAMHSLDHPNLIRLYGVVLSSPLMMVTELAPL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAG 499
Cdd:cd05040  82 GSLLDRLRKDQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQNEDHYVMQEHR 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQ-GKRMECPPECPPELYALMSDCWIY 578
Cdd:cd05040 162 KVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDKeGERLERPDDCPQDIYNVMLQCWAH 241

                ....*...
gi 31455611 579 KWEDRPDF 586
Cdd:cd05040 242 KPADRPTF 249
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
343-589 1.60e-82

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 260.00  E-value: 1.60e-82
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQ-IDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGG 420
Cdd:cd05033  11 VIGGGEFGEVCSGSLKLPGKKeIDVAIKTLKSGYSDKQRLDFLTEASIMGQFDHPNVIRLEGVVtKSRPVMIVTEYMENG 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSaGK 500
Cdd:cd05033  91 SLDKFLRENDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLEDSEATYTTKG-GK 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd05033 170 IPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSALYQLMLDCWQKDR 249

                ....*....
gi 31455611 581 EDRPDFLTV 589
Cdd:cd05033 250 NERPTFSQI 258
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
344-586 4.88e-81

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 255.67  E-value: 4.88e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmrkKQIDVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPL 422
Cdd:cd05034   3 LGAGQFGEVWMGVWN---GTTKVAVKTLKPGT--MSPEAFLQEAQIMKKLRHDKLVQLYAVCsDEEPIYIVTELMSKGSL 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLvgKREEIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAG 499
Cdd:cd05034  78 LDYL--RTGEGRALRLPQLIDmaaQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLI--EDDEYTAREGA 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:cd05034 154 KFPIKWTAPEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKKE 233

                ....*..
gi 31455611 580 WEDRPDF 586
Cdd:cd05034 234 PEERPTF 240
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
344-586 6.94e-81

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 256.19  E-value: 6.94e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYR--MRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGP 421
Cdd:cd05057  15 LGSGAFGTVYKGVWIpeGEKVKIPVAIKVLREETGPKANEEILDEAYVMASVDHPHLVRLLGICLSSQVQLITQLMPLGC 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArSAGKW 501
Cdd:cd05057  95 LLDYVRNHRDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLDVDEKEYHA-EGGKV 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05057 174 PIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDVYMVLVKCWMIDAE 253

                ....*
gi 31455611 582 DRPDF 586
Cdd:cd05057 254 SRPTF 258
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
344-593 2.75e-78

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 249.25  E-value: 2.75e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYrmrKKQIDVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPL 422
Cdd:cd05068  16 LGSGQFGEVWEGLW---NNTTPVAVKTLKPGT--MDPEDFLREAQIMKKLRHPKLIQLYAVCtLEEPIYIITELMKHGSL 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYyTARSAGKWP 502
Cdd:cd05068  91 LEYLQGKGRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKVEDEY-EAREGAKFP 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 503 LKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWED 582
Cdd:cd05068 170 IKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYDIMLECWKADPME 249
                       250
                ....*....|.
gi 31455611 583 RPDFLTVEQRM 593
Cdd:cd05068 250 RPTFETLQWKL 260
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
333-593 2.79e-75

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 241.10  E-value: 2.79e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 333 KRDNLLIADIelGCGNFGSVRQGVYRMRKkqidVAIKVLKQGTEKADteEMMREAQIMHQLDNPYIVRLIGVC-QAEALM 411
Cdd:cd05039   5 KKDLKLGELI--GKGEFGDVMLGDYRGQK----VAVKCLKDDSTAAQ--AFLAEASVMTTLRHPNLVQLLGVVlEGNGLY 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 412 LVMEMAGGGPLHKFLVGK-REEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKalgadD 490
Cdd:cd05039  77 IVTEYMAKGSLVDYLRSRgRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAK-----E 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTARSaGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYA 570
Cdd:cd05039 152 ASSNQDG-GKLPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYK 230
                       250       260
                ....*....|....*....|...
gi 31455611 571 LMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd05039 231 VMKNCWELDPAKRPTFKQLREKL 253
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
344-586 1.07e-74

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 240.36  E-value: 1.07e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYR-MRKKQID-VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE---ALMLVMEMAG 418
Cdd:cd05038  12 LGEGHFGSVELCRYDpLGDNTGEqVAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCESPgrrSLRLIMEYLP 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSA 498
Cdd:cd05038  92 SGSLRDYLQRHRDQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPEDKEYYYVKEP 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 499 GKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQ--------------GKRMECPPEC 564
Cdd:cd05038 172 GESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPSQSPPALFLRMIGIAQgqmivtrllellksGERLPRPPSC 251
                       250       260
                ....*....|....*....|..
gi 31455611 565 PPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05038 252 PDEVYDLMKECWEYEPQDRPSF 273
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
344-591 1.11e-72

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 233.88  E-value: 1.11e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmrKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPL 422
Cdd:cd05041   3 IGRGNFGDVYRGVLK--PDNTEVAVKTCRETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCvQKQPIMIVMELVPGGSL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlgADDSYYTARSA-GKW 501
Cdd:cd05041  81 LTFLRKKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSRE--EEDGEYTVSDGlKQI 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05041 159 PIKWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPE 238
                       250
                ....*....|
gi 31455611 582 DRPDFLTVEQ 591
Cdd:cd05041 239 NRPSFSEIYN 248
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
152-255 3.57e-72

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 227.11  E-value: 3.57e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 152 LIATTAHERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDT 231
Cdd:cd10402   1 LIATTAHERMPWYHGSIARDEAERRLYSGAQPDGKFLLRERKESGTYALSLVYGKTVYHYRIDQDKSGKYSIPEGTKFDT 80
                        90       100
                ....*....|....*....|....
gi 31455611 232 LWQLVEYLKLKADGLIYCLKEACP 255
Cdd:cd10402  81 LWQLVEYLKLKPDGLIFVLRESCP 104
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
344-586 4.27e-70

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 227.83  E-value: 4.27e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMR-KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAGGGP 421
Cdd:cd05065  12 IGAGEFGEVCRGRLKLPgKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVvTKSRPVMIITEFMENGA 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL--GADDSYYTARSAG 499
Cdd:cd05065  92 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLedDTSDPTYTSSLGG 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:cd05065 172 KIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTALHQLMLDCWQKD 251

                ....*..
gi 31455611 580 WEDRPDF 586
Cdd:cd05065 252 RNLRPKF 258
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
343-589 3.10e-69

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 225.02  E-value: 3.10e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmrkKQIDVAIKVLKQGTEKADteEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd05059  11 ELGSGQFGVVHLGKWR---GKIDVAIKMIKEGSMSED--DFIEEAKVMMKLSHPKLVQLYGVCtKQRPIFIVTEYMANGC 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYyTARSAGKW 501
Cdd:cd05059  86 LLNYLRERRGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYV-LDDEY-TSSVGTKF 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05059 164 PVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHEKPE 243

                ....*...
gi 31455611 582 DRPDFLTV 589
Cdd:cd05059 244 ERPTFKIL 251
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
344-586 1.41e-68

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 223.70  E-value: 1.41e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMR-KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAGGGP 421
Cdd:cd05063  13 IGAGEFGEVFRGILKMPgRKEVAVAIKTLKPGYTEKQRQDFLSEASIMGQFSHHNIIRLEGVvTKFKPAMIITEYMENGA 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKW 501
Cdd:cd05063  93 LDKYLRDHDGEFSSYQLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLEDDPEGTYTTSGGKI 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05063 173 PIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSAVYQLMLQCWQQDRA 252

                ....*
gi 31455611 582 DRPDF 586
Cdd:cd05063 253 RRPRF 257
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
344-586 1.46e-68

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 223.59  E-value: 1.46e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMR---KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:cd05066  12 IGAGEFGEVCSG--RLKlpgKREIPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVtRSKPVMIVTEYMEN 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD-DSYYTARsA 498
Cdd:cd05066  90 GSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDpEAAYTTR-G 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 499 GKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIY 578
Cdd:cd05066 169 GKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQLMLDCWQK 248

                ....*...
gi 31455611 579 KWEDRPDF 586
Cdd:cd05066 249 DRNERPKF 256
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
344-586 5.34e-68

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 223.75  E-value: 5.34e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVY--RMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGP 421
Cdd:cd05108  15 LGSGAFGTVYKGLWipEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGC 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArSAGKW 501
Cdd:cd05108  95 LLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHA-EGGKV 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05108 174 PIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDAD 253

                ....*
gi 31455611 582 DRPDF 586
Cdd:cd05108 254 SRPKF 258
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
344-593 9.34e-68

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 221.53  E-value: 9.34e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmrKKQIDVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVME-MAGGGP 421
Cdd:cd05052  14 LGGGQYGEVYEGVWK--KYNLTVAVKTLKEDT--MEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPpFYIITEfMPYGNL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsyYTARSAGKW 501
Cdd:cd05052  90 LDYLRECNREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT--YTAHAGAKF 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05052 168 PIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRACWQWNPS 247
                       250
                ....*....|..
gi 31455611 582 DRPDFLTVEQRM 593
Cdd:cd05052 248 DRPSFAEIHQAL 259
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
8-111 1.12e-67

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 215.34  E-value: 1.12e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   8 LPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFY 87
Cdd:cd09938   1 LPFFYGSITREEAEEYLKLAGMSDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIERQLNGTYAIAGGKAHCGPAELCEYH 80
                        90       100
                ....*....|....*....|....
gi 31455611  88 SRDPDGLPCNLRKPCNRPSGLEPQ 111
Cdd:cd09938  81 STDLDGLVCLLRKPCNRPPGVEPK 104
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
334-586 1.70e-67

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 220.91  E-value: 1.70e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 334 RDNLLIADiELGCGNFGSVRQGVYRMRKKqidVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLV 413
Cdd:cd05067   6 RETLKLVE-RLGAGQFGEVWMGYYNGHTK---VAIKSLKQGS--MSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYII 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 414 MEMAGGGPLHKFL-VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSY 492
Cdd:cd05067  80 TEYMENGSLVDFLkTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLI--EDNE 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALM 572
Cdd:cd05067 158 YTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQLM 237
                       250
                ....*....|....
gi 31455611 573 SDCWIYKWEDRPDF 586
Cdd:cd05067 238 RLCWKERPEDRPTF 251
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
344-595 2.98e-67

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 219.88  E-value: 2.98e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYrmrKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPL 422
Cdd:cd05085   4 LGKGNFGEVYKGTL---KDKTPVAVKTCKEDLPQELKIKFLSEARILKQYDHPNIVKLIGVCtQRQPIYIVMELVPGGDF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlgADDSYYTARSAGKWP 502
Cdd:cd05085  81 LSFLRKKKDELKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRQ--EDDGVYSSSGLKQIP 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 503 LKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWED 582
Cdd:cd05085 159 IKWTAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNPEN 238
                       250
                ....*....|...
gi 31455611 583 RPDFLTVEQRMRA 595
Cdd:cd05085 239 RPKFSELQKELAA 251
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
344-586 9.49e-67

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 218.83  E-value: 9.49e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYR----MRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAG 418
Cdd:cd05044   3 LGSGAFGEVFEGTAKdilgDGSGETKVAVKTLRKGATDQEKAEFLKEAHLMSNFKHPNILKLLGVClDNDPQYIILELME 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREEIPVSNVAELLHQVSM------GMKYLEEKNFVHRDLAARNVLLVNRHYA----KISDFGLSKALGA 488
Cdd:cd05044  83 GGDLLSYLRAARPTAFTPPLLTLKDLLSIcvdvakGCVYLEDMHFVHRDLAARNCLVSSKDYRervvKIGDFGLARDIYK 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 489 DDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPEL 568
Cdd:cd05044 163 ND-YYRKEGEGLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAGGRLDQPDNCPDDL 241
                       250
                ....*....|....*...
gi 31455611 569 YALMSDCWIYKWEDRPDF 586
Cdd:cd05044 242 YELMLRCWSTDPEERPSF 259
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
343-593 2.16e-66

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 217.49  E-value: 2.16e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd05084   3 RIGRGNFGEVFSG--RLRADNTPVAVKSCRETLPPDLKAKFLQEARILKQYSHPNIVRLIGVCtQKQPIYIVMELVQGGD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlgADDSYYTARSAGKW 501
Cdd:cd05084  81 FLTFLRTEGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSRE--EEDGVYAATGGMKQ 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 -PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd05084 159 iPVKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYDP 238
                       250
                ....*....|...
gi 31455611 581 EDRPDFLTVEQRM 593
Cdd:cd05084 239 RKRPSFSTVHQDL 251
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
344-586 2.23e-63

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 210.65  E-value: 2.23e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVY--RMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGP 421
Cdd:cd05109  15 LGSGAFGTVYKGIWipDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLTSTVQLVTQLMPYGC 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArSAGKW 501
Cdd:cd05109  95 LLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHA-DGGKV 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05109 174 PIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 253

                ....*
gi 31455611 582 DRPDF 586
Cdd:cd05109 254 CRPRF 258
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
343-595 2.78e-63

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 209.60  E-value: 2.78e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKqidVAIKVLKQgTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd05148  13 KLGSGYFGEVWEGLWKNRVR---VAIKILKS-DDLLKQQDFQKEVQALKRLRHKHLISLFAVCsVGEPVYIITELMEKGS 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAgK 500
Cdd:cd05148  89 LLAFLRSPEGQvLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLI--KEDVYLSSDK-K 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd05148 166 IPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIMLECWAAEP 245
                       250
                ....*....|....*
gi 31455611 581 EDRPDFLTVEQRMRA 595
Cdd:cd05148 246 EDRPSFKALREELDN 260
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
343-595 3.98e-62

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 207.23  E-value: 3.98e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQG---VYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVM-EMAG 418
Cdd:cd05048  12 ELGEGAFGKVYKGellGPSSEESAISVAIKTLKENASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKEQPQCMLfEYMA 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLV------------GKREEIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS 483
Cdd:cd05048  92 HGDLHEFLVrhsphsdvgvssDDDGTASSLDQSDFLHiaiQIAAGMEYLSSHHYVHRDLAARNCLVGDGLTVKISDFGLS 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 484 KALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPE 563
Cdd:cd05048 172 RDIYSSD-YYRVQSKSLLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIEMIRSRQLLPCPED 250
                       250       260       270
                ....*....|....*....|....*....|..
gi 31455611 564 CPPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd05048 251 CPARVYSLMVECWHEIPSRRPRFKEIHTRLRT 282
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
343-586 7.82e-62

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 206.05  E-value: 7.82e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKqidVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd05072  14 KLGAGQFGEVWMGYYNNSTK---VAVKTLKPGT--MSVQAFLEEANLMKTLQHDKLVRLYAVVtKEEPIYIITEYMAKGS 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFL---VGKREEIPvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSA 498
Cdd:cd05072  89 LLDFLksdEGGKVLLP--KLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVI--EDNEYTAREG 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 499 GKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIY 578
Cdd:cd05072 165 AKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYDIMKTCWKE 244

                ....*...
gi 31455611 579 KWEDRPDF 586
Cdd:cd05072 245 KAEERPTF 252
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
342-586 1.17e-61

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 205.18  E-value: 1.17e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGVYRMRKKqidVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGG 420
Cdd:cd05112  10 QEIGSGQFGLVHLGYWLNKDK---VAIKTIREGA--MSEEDFIEEAEVMMKLSHPKLVQLYGVClEQAPICLVFEFMEHG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYyTARSAGK 500
Cdd:cd05112  85 CLSDYLRTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFV-LDDQY-TSSTGTK 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd05112 163 FPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKERP 242

                ....*.
gi 31455611 581 EDRPDF 586
Cdd:cd05112 243 EDRPSF 248
SH2_C-SH2_Zap70_Syk_like cd10345
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
162-255 2.21e-61

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198208  Cd Length: 95  Bit Score: 198.76  E-value: 2.21e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 162 PWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYLKL 241
Cdd:cd10345   1 PWFHGKISREESEQIVLIGSKTNGKFLIRARDNNGSYALCLLHEGKVLHYRIDKDKTGKLSIPEGKKFDTLWQLVEHYSY 80
                        90
                ....*....|....
gi 31455611 242 KADGLIYCLKEACP 255
Cdd:cd10345  81 KADGLLRVLTVPCQ 94
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
332-587 4.23e-61

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 204.50  E-value: 4.23e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 332 LKRDNLLIADiELGCGNFGSVRQGVYRMRKK---QIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QA 407
Cdd:cd05032   3 LPREKITLIR-ELGQGSFGMVYEGLAKGVVKgepETRVAIKTVNENASMRERIEFLNEASVMKEFNCHHVVRLLGVVsTG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 408 EALMLVMEMAGGGPLHKFLVGKREEIPVSNV-----AELLH----QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKIS 478
Cdd:cd05032  82 QPTLVVMELMAKGDLKSYLRSRRPEAENNPGlgpptLQKFIqmaaEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 479 DFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRM 558
Cdd:cd05032 162 DFGMTRDIYETD-YYRKGGKGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGHL 240
                       250       260
                ....*....|....*....|....*....
gi 31455611 559 ECPPECPPELYALMSDCWIYKWEDRPDFL 587
Cdd:cd05032 241 DLPENCPDKLLELMRMCWQYNPKMRPTFL 269
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
334-593 4.80e-61

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 204.16  E-value: 4.80e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 334 RDNL-LIAdiELGCGNFGSVRQGVYRMR---KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAE 408
Cdd:cd05036   5 RKNLtLIR--ALGQGAFGEVYEGTVSGMpgdPSPLQVAVKTLPELCSEQDEMDFLMEALIMSKFNHPNIVRCIGVCfQRL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 409 ALMLVMEMAGGGPLHKFL------VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN---RHYAKISD 479
Cdd:cd05036  83 PRFILLELMAGGDLKSFLrenrprPEQPSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCkgpGRVAKIGD 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 480 FGLSKALGADDsYYtaRSAGK--WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKR 557
Cdd:cd05036 163 FGMARDIYRAD-YY--RKGGKamLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSGGR 239
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 31455611 558 MECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd05036 240 MDPPKNCPGPVYRIMTQCWQHIPEDRPNFSTILERL 275
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
344-593 1.15e-60

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 202.00  E-value: 1.15e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmrkkQIDVAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGP 421
Cdd:cd13999   1 IGSGSFGEVYKGKWR----GTDVAIKKLKVEDDNDELLKEfRREVSILSKLRHPNIVQFIGACLSPPpLCIVTEYMPGGS 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgadDSYYTARSAGKW 501
Cdd:cd13999  77 LYDLLHKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIK---NSTTEKMTGVVG 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAF-IEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd13999 154 TPRWMAPEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIAAAvVQKGLRPPIPPDCPPELSKLIKRCWNEDP 232
                       250
                ....*....|...
gi 31455611 581 EDRPDFLTVEQRM 593
Cdd:cd13999 233 EKRPSFSEIVKRL 245
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
344-586 1.17e-60

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 204.14  E-value: 1.17e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKK--QIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGP 421
Cdd:cd05110  15 LGSGAFGTVYKGIWVPEGEtvKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPTIQLVTQLMPHGC 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArSAGKW 501
Cdd:cd05110  95 LLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNA-DGGKM 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05110 174 PIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDAD 253

                ....*
gi 31455611 582 DRPDF 586
Cdd:cd05110 254 SRPKF 258
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
344-593 7.17e-60

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 200.48  E-value: 7.17e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKkqidVAIKVLKQgteKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGPLH 423
Cdd:cd05083  14 IGEGEFGAVLQGEYMGQK----VAVKNIKC---DVTAQAFLEETAVMTKLQHKNLVRLLGVILHNGLYIVMELMSKGNLV 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 424 KFLVGK-REEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKA--LGADDSyytarsagK 500
Cdd:cd05083  87 NFLRSRgRALVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKVgsMGVDNS--------R 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd05083 159 LPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMTSCWEAEP 238
                       250
                ....*....|...
gi 31455611 581 EDRPDFLTVEQRM 593
Cdd:cd05083 239 GKRPSFKKLREKL 251
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
344-586 3.19e-59

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 199.30  E-value: 3.19e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKK-QIDVAIKVLK-QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEAL------MLVM 414
Cdd:cd05035   7 LGEGEFGSVMEAQLKQDDGsQLKVAVKTMKvDIHTYSEIEEFLSEAACMKDFDHPNVMRLIGVCfTASDLnkppspMVIL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLVGKR-----EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD 489
Cdd:cd05035  87 PFMKHGDLHSYLLYSRlgglpEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLSRKIYSG 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 DsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELY 569
Cdd:cd05035 167 D-YYRQGRISKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPEDCLDEVY 245
                       250
                ....*....|....*..
gi 31455611 570 ALMSDCWIYKWEDRPDF 586
Cdd:cd05035 246 FLMYFCWTVDPKDRPTF 262
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
344-600 3.71e-59

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 199.46  E-value: 3.71e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGT-EKADTEEMMREAQIMHQLDNPYIVRLIGVC----QAEAL---MLVME 415
Cdd:cd05075   8 LGEGEFGSVMEGQLNQDDSVLKVAVKTMKIAIcTRSEMEDFLSEAVCMKEFDHPNVMRLIGVClqntESEGYpspVVILP 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKFLVGKR-----EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADD 490
Cdd:cd05075  88 FMKHGDLHSFLLYSRlgdcpVYLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGLSKKIYNGD 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTARSAgKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYA 570
Cdd:cd05075 168 YYRQGRIS-KMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPPDCLDGLYE 246
                       250       260       270
                ....*....|....*....|....*....|
gi 31455611 571 LMSDCWIYKWEDRPDFLTVEQRMRACYYSL 600
Cdd:cd05075 247 LMSSCWLLNPKDRPSFETLRCELEKILKDL 276
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
343-586 9.62e-59

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 197.06  E-value: 9.62e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKqidVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGPL 422
Cdd:cd14203   2 KLGQGCFGEVWMGTWNGTTK---VAIKTLKPGT--MSPEAFLEEAQIMKKLRHDKLVQLYAVVSEEPIYIVTEFMSKGSL 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLV-GKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAGKW 501
Cdd:cd14203  77 LDFLKdGEGKYLKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLI--EDNEYTARQGAKF 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd14203 155 PIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKDPE 234

                ....*
gi 31455611 582 DRPDF 586
Cdd:cd14203 235 ERPTF 239
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
327-589 1.25e-58

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 198.41  E-value: 1.25e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 327 DKKLFLKRDNLLIADIeLGCGNFGSVRQGVYR----MRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQL-DNPYIVRL 401
Cdd:cd05053   4 DPEWELPRDRLTLGKP-LGEGAFGQVVKAEAVgldnKPNEVVTVAVKMLKDDATEKDLSDLVSEMEMMKMIgKHKNIINL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 402 IGVC-QAEALMLVMEMAGGGPLHKFLVGKR---------------EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAAR 465
Cdd:cd05053  83 LGACtQDGPLYVVVEYASKGNLREFLRARRppgeeaspddprvpeEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAAR 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 466 NVLLVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKG 545
Cdd:cd05053 163 NVLVTEDNVMKIADFGLARDIHHID-YYRKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPV 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 31455611 546 PEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFLTV 589
Cdd:cd05053 242 EELFKLLKEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQL 285
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
366-586 6.54e-58

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 196.40  E-value: 6.54e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 366 VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPLHKFLvgkREEIPVSNVAE---- 440
Cdd:cd05051  49 VAVKMLRPDASKNAREDFLKEVKIMSQLKDPNIVRLLGVCtRDEPLCMIVEYMENGDLNQFL---QKHEAETQGASatns 125
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 441 -------LLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPEC 510
Cdd:cd05051 126 ktlsygtLLYmatQIASGMKYLESLNFVHRDLATRNCLVGPNYTIKIADFGMSRNLYSGD-YYRIEGRAVLPIRWMAWES 204
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 511 INFRKFSSRSDVWSYGVTMWEALSYGQK-PYKKMKGPEVMA-----FIEQGKR--MECPPECPPELYALMSDCWIYKWED 582
Cdd:cd05051 205 ILLGKFTTKSDVWAFGVTLWEILTLCKEqPYEHLTDEQVIEnagefFRDDGMEvyLSRPPNCPKEIYELMLECWRRDEED 284

                ....
gi 31455611 583 RPDF 586
Cdd:cd05051 285 RPTF 288
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
343-589 8.09e-58

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 196.21  E-value: 8.09e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQ----GVYRMRKKQIdVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMA 417
Cdd:cd05050  12 DIGQGAFGRVFQarapGLLPYEPFTM-VAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCaVGKPMCLLFEYM 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFL-------------VGKREEIPVSNVAEL--LHQVSM------GMKYLEEKNFVHRDLAARNVLLVNRHYAK 476
Cdd:cd05050  91 AYGDLNEFLrhrspraqcslshSTSSARKCGLNPLPLscTEQLCIakqvaaGMAYLSERKFVHRDLATRNCLVGENMVVK 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 477 ISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGK 556
Cdd:cd05050 171 IADFGLSRNIYSAD-YYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHEEVIYYVRDGN 249
                       250       260       270
                ....*....|....*....|....*....|...
gi 31455611 557 RMECPPECPPELYALMSDCWIYKWEDRPDFLTV 589
Cdd:cd05050 250 VLSCPDNCPLELYNLMRLCWSKLPSDRPSFASI 282
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
332-595 1.67e-57

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 194.99  E-value: 1.67e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 332 LKRDNLLIADiELGCGNFGSVRQG-VYRMRKKQ--IDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QA 407
Cdd:cd05049   2 IKRDTIVLKR-ELGEGAFGKVFLGeCYNLEPEQdkMLVAVKTLKDASSPDARKDFEREAELLTNLQHENIVKFYGVCtEG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 408 EALMLVME-MAGG---------GPLHKFLVGKREEIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHY 474
Cdd:cd05049  81 DPLLMVFEyMEHGdlnkflrshGPDAAFLASEDSAPGELTLSQLLHiavQIASGMVYLASQHFVHRDLATRNCLVGTNLV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 475 AKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQ 554
Cdd:cd05049 161 VKIGDFGMSRDIYSTD-YYRVGGHTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIECITQ 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 31455611 555 GKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd05049 240 GRLLQRPRTCPSEVYAVMLGCWKREPQQRLNIKDIHKRLQE 280
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
328-586 1.89e-57

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 195.15  E-value: 1.89e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 328 KKLFLKRdnllIADieLGCGNFGSVRQGVYRMRKKQID--VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC 405
Cdd:cd05079   2 EKRFLKR----IRD--LGEGHFGKVELCRYDPEGDNTGeqVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGIC 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 406 QAE---ALMLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGL 482
Cdd:cd05079  76 TEDggnGIKLIMEFLPSGSLKEYLPRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGL 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 483 SKALGADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYK------KMKGP--------EV 548
Cdd:cd05079 156 TKAIETDKEYYTVKDDLDSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCDSESSpmtlflKMIGPthgqmtvtRL 235
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 31455611 549 MAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05079 236 VRVLEEGKRLPRPPNCPEEVYQLMRKCWEFQPSKRTTF 273
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
344-595 1.98e-57

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 194.75  E-value: 1.98e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQI-DVAIKVLKQGT-EKADTEEMMREAQIMHQLDNPYIVRLIGVC-------QAEALMLVM 414
Cdd:cd05074  17 LGKGEFGSVREAQLKSEDGSFqKVAVKMLKADIfSSSDIEEFLREAACMKEFDHPNVIKLIGVSlrsrakgRLPIPMVIL 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLVGKR--EE---IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD 489
Cdd:cd05074  97 PFMKHGDLHTFLLMSRigEEpftLPLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVADFGLSKKIYSG 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 DsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELY 569
Cdd:cd05074 177 D-YYRQGCASKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGNRLKQPPDCLEDVY 255
                       250       260
                ....*....|....*....|....*.
gi 31455611 570 ALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd05074 256 ELMCQCWSPEPKCRPSFQHLRDQLEL 281
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
321-586 2.10e-57

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 193.94  E-value: 2.10e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 321 DPEELKdkklFLKrdnlliadiELGCGNFGSVRQGVYRmrkKQIDVAIKVLKQGTEKADteEMMREAQIMHQLDNPYIVR 400
Cdd:cd05113   2 DPKDLT----FLK---------ELGTGQFGVVKYGKWR---GQYDVAIKMIKEGSMSED--EFIEEAKVMMNLSHEKLVQ 63
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 401 LIGVCQAE-ALMLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISD 479
Cdd:cd05113  64 LYGVCTKQrPIFIITEYMANGCLLNYLREMRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSD 143
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 480 FGLSKALGADDsyYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRME 559
Cdd:cd05113 144 FGLSRYVLDDE--YTSSVGSKFPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLY 221
                       250       260
                ....*....|....*....|....*..
gi 31455611 560 CPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05113 222 RPHLASEKVYTIMYSCWHEKADERPTF 248
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
341-586 2.57e-57

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 194.09  E-value: 2.57e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 341 DIELGCGNFGSVRQGVYrmrKKQIDVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGG 420
Cdd:cd05073  16 EKKLGAGQFGEVWMATY---NKHTKVAVKTMKPGS--MSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKG 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLvgKREE---IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARS 497
Cdd:cd05073  91 SLLDFL--KSDEgskQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVI--EDNEYTARE 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 AGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWI 577
Cdd:cd05073 167 GAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWK 246

                ....*....
gi 31455611 578 YKWEDRPDF 586
Cdd:cd05073 247 NRPEERPTF 255
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
322-586 1.01e-56

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 192.86  E-value: 1.01e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 322 PEELKDKKLflkrdnlliadieLGCGNFGSVRQGVY--RMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIV 399
Cdd:cd05111   6 ETELRKLKV-------------LGSGVFGTVHKGIWipEGDSIKIPVAIKVIQDRSGRQSFQAVTDHMLAIGSLDHAYIV 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 400 RLIGVCQAEALMLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISD 479
Cdd:cd05111  73 RLLGICPGASLQLVTQLLPLGSLLDHVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVAD 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 480 FGLSKALGADDSYYTARSAgKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRME 559
Cdd:cd05111 153 FGVADLLYPDDKKYFYSEA-KTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLA 231
                       250       260
                ....*....|....*....|....*..
gi 31455611 560 CPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05111 232 QPQICTIDVYMVMVKCWMIDENIRPTF 258
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
327-594 1.10e-56

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 194.03  E-value: 1.10e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 327 DKKLFLKRDNLLIADiELGCGNFGSV-RQGVYRMRKKQID----VAIKVLKQGTEKADTEEMMREAQIMHQLD-NPYIVR 400
Cdd:cd05099   4 DPKWEFPRDRLVLGK-PLGEGCFGQVvRAEAYGIDKSRPDqtvtVAVKMLKDNATDKDLADLISEMELMKLIGkHKNIIN 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 401 LIGVCQAEA-LMLVMEMAGGGPLHKFLVGKR---------------EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAA 464
Cdd:cd05099  83 LLGVCTQEGpLYVIVEYAAKGNLREFLRARRppgpdytfditkvpeEQLSFKDLVSCAYQVARGMEYLESRRCIHRDLAA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 465 RNVLLVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMK 544
Cdd:cd05099 163 RNVLVTEDNVMKIADFGLARGVHDID-YYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIP 241
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 545 GPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMR 594
Cdd:cd05099 242 VEELFKLLREGHRMDKPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALD 291
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
344-586 2.23e-56

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 191.68  E-value: 2.23e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRM-RKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAGGGP 421
Cdd:cd05064  13 LGTGRFGELCRGCLKLpSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGViTRGNTMMIVTEYMSNGA 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARsaGKW 501
Cdd:cd05064  93 LDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRRLQEDKSEAIYTTMS--GKS 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05064 171 PVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLHQLMLDCWQKERG 250

                ....*
gi 31455611 582 DRPDF 586
Cdd:cd05064 251 ERPRF 255
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
344-594 5.53e-56

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 190.19  E-value: 5.53e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKkqidVAIKVLKQgteKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE--ALMLVMEMAGGGP 421
Cdd:cd05082  14 IGKGEFGDVMLGDYRGNK----VAVKCIKN---DATAQAFLAEASVMTQLRHSNLVQLLGVIVEEkgGLYIVTEYMAKGS 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGK-REEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAddsyytARSAGK 500
Cdd:cd05082  87 LVDYLRSRgRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASS------TQDTGK 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd05082 161 LPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDVMKNCWHLDA 240
                       250
                ....*....|....
gi 31455611 581 EDRPDFLTVEQRMR 594
Cdd:cd05082 241 AMRPSFLQLREQLE 254
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
336-600 1.32e-55

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 190.15  E-value: 1.32e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 336 NLLIADIELGCGNFGSVRQGvyrmRKKQID-----VAIKVLK-QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC---- 405
Cdd:cd14204   7 NLLSLGKVLGEGEFGSVMEG----ELQQPDgtnhkVAVKTMKlDNFSQREIEEFLSEAACMKDFNHPNVIRLLGVClevg 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 406 --QAEALMLVMEMAGGGPLHKFLVGKREE-----IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKIS 478
Cdd:cd14204  83 sqRIPKPMVILPFMKYGDLHSFLLRSRLGsgpqhVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 479 DFGLSKALGADDSYYTARSAgKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRM 558
Cdd:cd14204 163 DFGLSKKIYSGDYYRQGRIA-KMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHRL 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 31455611 559 ECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRACYYSL 600
Cdd:cd14204 242 KQPEDCLDELYDIMYSCWRSDPTDRPTFTQLRENLEKLLESL 283
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
343-587 6.44e-55

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 187.38  E-value: 6.44e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmrkKQIDVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd05114  11 ELGSGLFGVVRLGKWR---AQYKVAIKAIREGA--MSEEDFIEEAKVMMKLTHPKLVQLYGVCtQQKPIYIVTEFMENGC 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsyYTARSAGKW 501
Cdd:cd05114  86 LLNYLRQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDDQ--YTSSSGAKF 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd05114 164 PVKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEKPE 243

                ....*.
gi 31455611 582 DRPDFL 587
Cdd:cd05114 244 GRPTFA 249
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
344-595 7.10e-54

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 185.48  E-value: 7.10e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQID--VAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQA---EALMLVMEMAG 418
Cdd:cd05081  12 LGKGNFGSVELCRYDPLGDNTGalVAVKQLQHSGPD-QQRDFQREIQILKALHSDFIVKYRGVSYGpgrRSLRLVMEYLP 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSA 498
Cdd:cd05081  91 SGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVREP 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 499 GKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKP------YKKMKGPE--------VMAFIEQGKRMECPPEC 564
Cdd:cd05081 171 GQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKScspsaeFLRMMGCErdvpalcrLLELLEEGQRLPAPPAC 250
                       250       260       270
                ....*....|....*....|....*....|.
gi 31455611 565 PPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd05081 251 PAEVHELMKLCWAPSPQDRPSFSALGPQLDM 281
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
343-586 1.02e-53

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 183.89  E-value: 1.02e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGP 421
Cdd:smart00220   6 KLGEGSFGKVYLARDKKTGKL--VAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEdKLYLVMEYCEGGD 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    422 LHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTarSAGkw 501
Cdd:smart00220  84 LFDLLK-KRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGEKLTT--FVG-- 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMA-FIEQGKR--MECPPECPPELYALMSDCWIY 578
Cdd:smart00220 159 TPEYMAPEVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDDQLLELFkKIGKPKPpfPPPEWDISPEAKDLIRKLLVK 237

                   ....*...
gi 31455611    579 KWEDRPDF 586
Cdd:smart00220 238 DPEKRLTA 245
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
343-595 1.73e-53

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 184.44  E-value: 1.73e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQG---VYRMRKKQIdVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIG-VCQAEALMLVMEMAG 418
Cdd:cd05090  12 ELGECAFGKIYKGhlyLPGMDHAQL-VAIKTLKDYNNPQQWNEFQQEASLMTELHHPNIVCLLGvVTQEQPVCMLFEFMN 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKReeiPVSNVA----------------ELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISD 479
Cdd:cd05090  91 QGDLHEFLIMRS---PHSDVGcssdedgtvkssldhgDFLHiaiQIAAGMEYLSSHFFVHKDLAARNILVGEQLHVKISD 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 480 FGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRME 559
Cdd:cd05090 168 LGLSREIYSSD-YYRVQNKSLLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVRKRQLLP 246
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 31455611 560 CPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd05090 247 CSEDCPPRMYSLMTECWQEIPSRRPRFKDIHARLRS 282
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
319-587 3.27e-53

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 184.23  E-value: 3.27e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 319 YSDPEELK-DKKLFLKRDNLLIADIeLGCGNFGSVRQGV-YRMRKKQ--IDVAIKVLKQGTEKADTEEMMREAQIMHQLD 394
Cdd:cd05055  18 YIDPTQLPyDLKWEFPRNNLSFGKT-LGAGAFGKVVEATaYGLSKSDavMKVAVKMLKPTAHSSEREALMSELKIMSHLG 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 395 NPY-IVRLIGVC-QAEALMLVMEMAGGGPLHKFLVGKREEIPVSNvaELLH---QVSMGMKYLEEKNFVHRDLAARNVLL 469
Cdd:cd05055  97 NHEnIVNLLGACtIGGPILVITEYCCYGDLLNFLRRKRESFLTLE--DLLSfsyQVAKGMAFLASKNCIHRDLAARNVLL 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 470 VNRHYAKISDFGLSKALgADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMkgPEVM 549
Cdd:cd05055 175 THGKIVKICDFGLARDI-MNDSNYVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGM--PVDS 251
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 31455611 550 AF---IEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFL 587
Cdd:cd05055 252 KFyklIKEGYRMAQPEHAPAEIYDIMKTCWDADPLKRPTFK 292
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
344-597 3.55e-53

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 182.67  E-value: 3.55e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVY-RMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC--QAEALMLVMEMAGGG 420
Cdd:cd05058   3 IGKGHFGCVYHGTLiDSDGQKIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGIClpSEGSPLVVLPYMKHG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLvgkREEIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYYTAR- 496
Cdd:cd05058  83 DLRNFI---RSETHNPTVKDLIGfglQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARDI-YDKEYYSVHn 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 497 -SAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDC 575
Cdd:cd05058 159 hTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVMLSC 238
                       250       260
                ....*....|....*....|..
gi 31455611 576 WIYKWEDRPDFLTVEQRMRACY 597
Cdd:cd05058 239 WHPKPEMRPTFSELVSRISQIF 260
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
343-595 3.90e-53

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 183.24  E-value: 3.90e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQG-VYRMRKKQ--IDVAIKVLKQGTEKAdTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAG 418
Cdd:cd05092  12 ELGEGAFGKVFLAeCHNLLPEQdkMLVAVKALKEATESA-RQDFQREAELLTVLQHQHIVRFYGVCtEGEPLIMVFEYMR 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLV-----------GKREEIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK 484
Cdd:cd05092  91 HGDLNRFLRshgpdakildgGEGQAPGQLTLGQMLQiasQIASGMVYLASLHFVHRDLATRNCLVGQGLVVKIGDFGMSR 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 485 ALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPEC 564
Cdd:cd05092 171 DIYSTD-YYRVGGRTMLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQGRELERPRTC 249
                       250       260       270
                ....*....|....*....|....*....|.
gi 31455611 565 PPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd05092 250 PPEVYAIMQGCWQREPQQRHSIKDIHSRLQA 280
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
343-591 4.69e-53

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 183.29  E-value: 4.69e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQID--VAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEA---LMLVMEMA 417
Cdd:cd14205  11 QLGKGNFGSVEMCRYDPLQDNTGevVAVKKLQHSTEE-HLRDFEREIEILKSLQHDNIVKYKGVCYSAGrrnLRLIMEYL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd14205  90 PYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKE 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 AGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKP------YKKMKGPE------VMAFIEQGK---RMECPP 562
Cdd:cd14205 170 PGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSksppaeFMRMIGNDkqgqmiVFHLIELLKnngRLPRPD 249
                       250       260       270
                ....*....|....*....|....*....|...
gi 31455611 563 ECPPELYALMSDCWIYKWEDRPDF----LTVEQ 591
Cdd:cd14205 250 GCPDEIYMIMTECWNNNVNQRPSFrdlaLRVDQ 282
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
338-586 6.80e-53

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 182.86  E-value: 6.80e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 338 LIADIELGCGNFGSVRQGV---YRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLV 413
Cdd:cd05045   2 LVLGKTLGEGEFGKVVKATafrLKGRAGYTTVAVKMLKENASSSELRDLLSEFNLLKQVNHPHVIKLYGACsQDGPLLLI 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 414 MEMAGGGPLHKFLVGKR-----------------------EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV 470
Cdd:cd05045  82 VEYAKYGSLRSFLRESRkvgpsylgsdgnrnssyldnpdeRALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLVA 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 471 NRHYAKISDFGLSKALGADDSYyTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMA 550
Cdd:cd05045 162 EGRKMKISDFGLSRDVYEEDSY-VKRSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFN 240
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 31455611 551 FIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05045 241 LLKTGYRMERPENCSEEMYNLMLTCWKQEPDKRPTF 276
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
343-595 3.65e-52

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 180.98  E-value: 3.65e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQG----VYRMRKKQIdVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMA 417
Cdd:cd05091  13 ELGEDRFGKVYKGhlfgTAPGEQTQA-VAIKTLKDKAEGPLREEFRHEAMLRSRLQHPNIVCLLGVVTKEQPMsMIFSYC 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKReeiPVSNV---------------AELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISD 479
Cdd:cd05091  92 SHGDLHEFLVMRS---PHSDVgstdddktvkstlepADFLHivtQIAAGMEYLSSHHVVHKDLATRNVLVFDKLNVKISD 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 480 FGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRME 559
Cdd:cd05091 169 LGLFREVYAAD-YYKLMGNSLLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVIEMIRNRQVLP 247
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 31455611 560 CPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd05091 248 CPDDCPAWVYTLMLECWNEFPSRRPRFKDIHSRLRT 283
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
332-586 4.82e-52

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 180.26  E-value: 4.82e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 332 LKRDNLLIADiELGCGNFGSVRQGVYRMRKKqidVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM 411
Cdd:cd05070   6 IPRESLQLIK-RLGNGQFGEVWMGTWNGNTK---VAIKTLKPGT--MSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 412 LVMEMAGGGPLHKFLV-GKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDD 490
Cdd:cd05070  80 IVTEYMSKGSLLDFLKdGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLI--ED 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYA 570
Cdd:cd05070 158 NEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHE 237
                       250
                ....*....|....*.
gi 31455611 571 LMSDCWIYKWEDRPDF 586
Cdd:cd05070 238 LMIHCWKKDPEERPTF 253
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
341-586 2.90e-51

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 178.34  E-value: 2.90e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 341 DIELGCGNFGSVRQGVYRMRKKqidVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGG 420
Cdd:cd05071  14 EVKLGQGCFGEVWMGTWNGTTR---VAIKTLKPGT--MSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMSKG 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAG 499
Cdd:cd05071  89 SLLDFLKGEMGKyLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLI--EDNEYTARQGA 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:cd05071 167 KFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLMCQCWRKE 246

                ....*..
gi 31455611 580 WEDRPDF 586
Cdd:cd05071 247 PEERPTF 253
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
334-594 4.68e-51

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 178.25  E-value: 4.68e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 334 RDNLLIADiELGCGNFGSVR------------QGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRL 401
Cdd:cd05097   4 RQQLRLKE-KLGEGQFGEVHlceaeglaeflgEGAPEFDGQPVLVAVKMLRADVTKTARNDFLKEIKIMSRLKNPNIIRL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 402 IGVC-QAEALMLVMEMAGGGPLHKFLvGKRE---------EIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVL 468
Cdd:cd05097  83 LGVCvSDDPLCMITEYMENGDLNQFL-SQREiestfthanNIPSVSIANLLYmavQIASGMKYLASLNFVHRDLATRNCL 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 469 LVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSY-GQKPYKKMKGPE 547
Cdd:cd05097 162 VGNHYTIKIADFGMSRNLYSGD-YYRIQGRAVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLcKEQPYSLLSDEQ 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 31455611 548 VMA-----FIEQGKR--MECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMR 594
Cdd:cd05097 241 VIEntgefFRNQGRQiyLSQTPLCPSPVFKLMMRCWSRDIKDRPTFNKIHHFLR 294
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
341-609 7.83e-51

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 177.19  E-value: 7.83e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 341 DIELGCGNFGSVRQGVYRMRKKqidVAIKVLKQGTekADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGG 420
Cdd:cd05069  17 DVKLGQGCFGEVWMGTWNGTTK---VAIKTLKPGT--MMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMGKG 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLV-GKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAG 499
Cdd:cd05069  92 SLLDFLKeGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLI--EDNEYTARQGA 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:cd05069 170 KFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCPESLHELMKLCWKKD 249
                       250       260       270
                ....*....|....*....|....*....|
gi 31455611 580 WEDRPDFLTVEQRMRAcyYSLASKVEGPPG 609
Cdd:cd05069 250 PDERPTFEYIQSFLED--YFTATEPQYQPG 277
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
344-586 1.11e-50

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 176.38  E-value: 1.11e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQL-DNPYIVRLIGVCQAEA-LMLVMEMAGGGP 421
Cdd:cd05047   3 IGEGNFGQVLKARIKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGyLYLAIEYAPHGN 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKR--EEIPVSNVA----------ELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAl 486
Cdd:cd05047  83 LLDFLRKSRvlETDPAFAIAnstastlssqQLLHfaaDVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 gadDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPP 566
Cdd:cd05047 162 ---QEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDD 238
                       250       260
                ....*....|....*....|
gi 31455611 567 ELYALMSDCWIYKWEDRPDF 586
Cdd:cd05047 239 EVYDLMRQCWREKPYERPSF 258
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
343-586 3.53e-50

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 175.47  E-value: 3.53e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqGVYRMRKKQID----VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQ---AEALMLVME 415
Cdd:cd05080  11 DLGEGHFGKV--SLYCYDPTNDGtgemVAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCCSeqgGKSLQLIME 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd05080  89 YVPLGSLRDYL--PKHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHEYYRV 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSY---GQKPYKK---MKGPE--------VMAFIEQGKRMECP 561
Cdd:cd05080 167 REDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHcdsSQSPPTKfleMIGIAqgqmtvvrLIELLERGERLPCP 246
                       250       260
                ....*....|....*....|....*
gi 31455611 562 PECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05080 247 DKCPQEVYHLMKNCWETEASFRPTF 271
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
342-586 2.26e-49

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 173.03  E-value: 2.26e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGvyrmRKKQID-------VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLV 413
Cdd:cd05046  11 TTLGRGEFGEVFLA----KAKGIEeeggetlVLVKALQKTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCrEAEPHYMI 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 414 MEMAGGGPLHKFLVGKREEIP--------VSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKA 485
Cdd:cd05046  87 LEYTDLGDLKQFLRATKSKDEklkppplsTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSKD 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 486 LGADDsYYTARSAgKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGK-RMECPPEC 564
Cdd:cd05046 167 VYNSE-YYKLRNA-LIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLQAGKlELPVPEGC 244
                       250       260
                ....*....|....*....|..
gi 31455611 565 PPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05046 245 PSRLYKLMTRCWAVNPKDRPSF 266
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
343-594 6.78e-49

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 172.08  E-value: 6.78e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYR-MRKKQID--VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAG 418
Cdd:cd05061  13 ELGQGSFGMVYEGNARdIIKGEAEtrVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVsKGQPTLVVMELMA 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREEI------PVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD 489
Cdd:cd05061  93 HGDLKSYLRSLRPEAennpgrPPPTLQEMIQmaaEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYET 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 DsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELY 569
Cdd:cd05061 173 D-YYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVT 251
                       250       260
                ....*....|....*....|....*
gi 31455611 570 ALMSDCWIYKWEDRPDFLTVEQRMR 594
Cdd:cd05061 252 DLMRMCWQFNPKMRPTFLEIVNLLK 276
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
332-586 8.56e-49

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 172.43  E-value: 8.56e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 332 LKRDNLLIADiELGCGNFGSVR-------------QGVYRMRK-KQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPY 397
Cdd:cd05096   2 FPRGHLLFKE-KLGEGQFGEVHlcevvnpqdlptlQFPFNVRKgRPLLVAVKILRPDANKNARNDFLKEVKILSRLKDPN 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 398 IVRLIGVC-QAEALMLVMEMAGGGPLHKFL---------------VGKREEIPVSNVAELLH---QVSMGMKYLEEKNFV 458
Cdd:cd05096  81 IIRLLGVCvDEDPLCMITEYMENGDLNQFLsshhlddkeengndaVPPAHCLPAISYSSLLHvalQIASGMKYLSSLNFV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 459 HRDLAARNVLLVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQ- 537
Cdd:cd05096 161 HRDLATRNCLVGENLTIKIADFGMSRNLYAGD-YYRIQGRAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEILMLCKe 239
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611 538 KPYKKMKGPEVMA-----FIEQGKRMEC--PPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05096 240 QPYGELTDEQVIEnagefFRDQGRQVYLfrPPPCPQGLYELMLQCWSRDCRERPSF 295
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
309-586 1.55e-48

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 172.12  E-value: 1.55e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 309 PMDTSVYEspYSDPEelkDKKLFLKRDNLLIADiELGCGNFGSVRQ----GVYRMRKKQ-IDVAIKVLKQGTEKADTEEM 383
Cdd:cd05101   3 PMLAGVSE--YELPE---DPKWEFPRDKLTLGK-PLGEGCFGQVVMaeavGIDKDKPKEaVTVAVKMLKDDATEKDLSDL 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 384 MREAQIMHQL-DNPYIVRLIGVC-QAEALMLVMEMAGGGPLHKFLVGKR---------------EEIPVSNVAELLHQVS 446
Cdd:cd05101  77 VSEMEMMKMIgKHKNIINLLGACtQDGPLYVIVEYASKGNLREYLRARRppgmeysydinrvpeEQMTFKDLVSCTYQLA 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 447 MGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYG 526
Cdd:cd05101 157 RGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNID-YYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFG 235
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 527 VTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05101 236 VLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTF 295
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
343-593 4.77e-47

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 167.48  E-value: 4.77e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVR----QGVYRMRKKQ----------IDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE 408
Cdd:cd05095  12 KLGEGQFGEVHlceaEGMEKFMDKDfalevsenqpVLVAVKMLRADANKNARNDFLKEIKIMSRLKDPNIIRLLAVCITD 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 409 -ALMLVMEMAGGGPLHKFLVGKREE-----------IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAK 476
Cdd:cd05095  92 dPLCMITEYMENGDLNQFLSRQQPEgqlalpsnaltVSYSDLRFMAAQIASGMKYLSSLNFVHRDLATRNCLVGKNYTIK 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 477 ISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQ-KPYKKMKGPEVMA----- 550
Cdd:cd05095 172 IADFGMSRNLYSGD-YYRIQGRAVLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFCReQPYSQLSDEQVIEntgef 250
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 31455611 551 FIEQGKRMECPPE--CPPELYALMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd05095 251 FRDQGRQTYLPQPalCPDSVYKLMLSCWRRDTKDRPSFQEIHTLL 295
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
344-593 5.80e-47

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 164.37  E-value: 5.80e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMAGGGPL 422
Cdd:cd00180   1 LGKGSFGKVYKARDKETGKK--VAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLyLVMEYCEGGSL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTaRSAGKWP 502
Cdd:cd00180  79 KDLLKENKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLK-TTGGTTP 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 503 LKWYAPECINFRKFSSRSDVWSYGVTMWEalsygqkpykkMkgpevmafieqgkrmecppecpPELYALMSDCWIYKWED 582
Cdd:cd00180 158 PYYAPPELLGGRYYGPKVDIWSLGVILYE-----------L----------------------EELKDLIRRMLQYDPKK 204
                       250
                ....*....|.
gi 31455611 583 RPDFLTVEQRM 593
Cdd:cd00180 205 RPSAKELLEHL 215
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
347-586 1.34e-46

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 165.70  E-value: 1.34e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 347 GNFGSVRQGVYRMRK-KQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC--QAEALMLVMEMAGGGPLH 423
Cdd:cd05043  17 GTFGRIFHGILRDEKgKEEEVLVKTVKDHASEIQVTMLLQESSLLYGLSHQNLLPILHVCieDGEKPMVLYPYMNWGNLK 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 424 KFL-----VGKREEIPVS--NVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsYYTAR 496
Cdd:cd05043  97 LFLqqcrlSEANNPQALStqQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALSRDLFPMD-YHCLG 175
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 497 SAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCW 576
Cdd:cd05043 176 DNENRPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQPINCPDELFAVMACCW 255
                       250
                ....*....|
gi 31455611 577 IYKWEDRPDF 586
Cdd:cd05043 256 ALDPEERPSF 265
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
326-586 2.00e-46

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 165.96  E-value: 2.00e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 326 KDKKLFLKRDNLLIADiELGCGNFGSVRQ----GVYRMRKKQI-DVAIKVLKQGTEKADTEEMMREAQIMHQL-DNPYIV 399
Cdd:cd05098   4 EDPRWELPRDRLVLGK-PLGEGCFGQVVLaeaiGLDKDKPNRVtKVAVKMLKSDATEKDLSDLISEMEMMKMIgKHKNII 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 400 RLIGVC-QAEALMLVMEMAGGGPLHKFLVGKR---------------EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLA 463
Cdd:cd05098  83 NLLGACtQDGPLYVIVEYASKGNLREYLQARRppgmeycynpshnpeEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 464 ARNVLLVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKM 543
Cdd:cd05098 163 ARNVLVTEDNVMKIADFGLARDIHHID-YYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGV 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 31455611 544 KGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05098 242 PVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTF 284
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
344-601 2.80e-46

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 165.17  E-value: 2.80e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQL-DNPYIVRLIGVCQAEA-LMLVMEMAGGGP 421
Cdd:cd05089  10 IGEGNFGQVIKAMIKKDGLKMNAAIKMLKEFASENDHRDFAGELEVLCKLgHHPNIINLLGACENRGyLYIAIEYAPYGN 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKR--EEIPV-------------SNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAl 486
Cdd:cd05089  90 LLDFLRKSRvlETDPAfakehgtastltsQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIADFGLSRG- 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 gadDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPP 566
Cdd:cd05089 169 ---EEVYVKKTMGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEKPRNCDD 245
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 31455611 567 ELYALMSDCWIYKWEDRPDF------LTVEQRMRACYYSLA 601
Cdd:cd05089 246 EVYELMRQCWRDRPYERPPFsqisvqLSRMLEARKAYVNMA 286
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
332-576 2.46e-45

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 162.52  E-value: 2.46e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 332 LKRDNLLIADiELGCGNFGSVRQG-VYRMRKKQ--IDVAIKVLKQGTEKAdTEEMMREAQIMHQLDNPYIVRLIGVC-QA 407
Cdd:cd05093   2 IKRHNIVLKR-ELGEGAFGKVFLAeCYNLCPEQdkILVAVKTLKDASDNA-RKDFHREAELLTNLQHEHIVKFYGVCvEG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 408 EALMLVMEMAGGGPLHKFLVG------------KREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA 475
Cdd:cd05093  80 DPLIMVFEYMKHGDLNKFLRAhgpdavlmaegnRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLV 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 476 KISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQG 555
Cdd:cd05093 160 KIGDFGMSRDVYSTD-YYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQG 238
                       250       260
                ....*....|....*....|.
gi 31455611 556 KRMECPPECPPELYALMSDCW 576
Cdd:cd05093 239 RVLQRPRTCPKEVYDLMLGCW 259
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
344-586 3.29e-45

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 161.02  E-value: 3.29e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRkkqiDVAIKVLKQGTEK--ADTEEMMR-EAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd14061   2 IGVGGFGKVYRGIWRGE----EVAVKAARQDPDEdiSVTLENVRqEARLFWMLRHPNIIALRGVCLQPPnLCLVMEYARG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKReeIPVSNVAELLHQVSMGMKYLEEKNFV---HRDLAARNVLLVNR--------HYAKISDFGLskalgA 488
Cdd:cd14061  78 GALNRVLAGRK--IPPHVLVDWAIQIARGMNYLHNEAPVpiiHRDLKSSNILILEAienedlenKTLKITDFGL-----A 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 489 DDSYYTAR--SAGKWplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK-RMECPPECP 565
Cdd:cd14061 151 REWHKTTRmsAAGTY--AWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKGIDGLAVAYGVAVNKlTLPIPSTCP 227
                       250       260
                ....*....|....*....|.
gi 31455611 566 PELYALMSDCWIYKWEDRPDF 586
Cdd:cd14061 228 EPFAQLMKDCWQPDPHDRPSF 248
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
343-589 1.36e-44

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 160.20  E-value: 1.36e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKK---QIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAG 418
Cdd:cd05062  13 ELGQGSFGMVYEGIAKGVVKdepETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVsQGQPTLVIMELMT 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREEI---------PVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD 489
Cdd:cd05062  93 RGDLKSYLRSLRPEMennpvqappSLKKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYET 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 DsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELY 569
Cdd:cd05062 173 D-YYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGLLDKPDNCPDMLF 251
                       250       260
                ....*....|....*....|
gi 31455611 570 ALMSDCWIYKWEDRPDFLTV 589
Cdd:cd05062 252 ELMRMCWQYNPKMRPSFLEI 271
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
334-586 1.70e-44

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 160.35  E-value: 1.70e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 334 RDNLLIADIeLGCGNFGSVRQGVYRMRKKQID---VAIKVLKQGTEKADTEEMMREAQIM----HQLDnpyIVRLIGVC- 405
Cdd:cd05054   6 RDRLKLGKP-LGRGAFGKVIQASAFGIDKSATcrtVAVKMLKEGATASEHKALMTELKILihigHHLN---VVNLLGACt 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 406 -QAEALMLVMEMAGGGPLHKFLVGKREEI------------PVSNVAELLH-------------QVSMGMKYLEEKNFVH 459
Cdd:cd05054  82 kPGGPLMVIVEFCKFGNLSNYLRSKREEFvpyrdkgardveEEEDDDELYKepltledlicysfQVARGMEFLASRKCIH 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 460 RDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAgKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKP 539
Cdd:cd05054 162 RDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGDA-RLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASP 240
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 540 YKKMK-GPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05054 241 YPGVQmDEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTF 288
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
327-586 2.75e-44

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 160.96  E-value: 2.75e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 327 DKKLFLKRDNLLIADiELGCGNFGSVRQ----GVYRMR-KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQL-DNPYIVR 400
Cdd:cd05100   4 DPKWELSRTRLTLGK-PLGEGCFGQVVMaeaiGIDKDKpNKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIgKHKNIIN 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 401 LIGVC-QAEALMLVMEMAGGGPLHKFLVGKR---------------EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAA 464
Cdd:cd05100  83 LLGACtQDGPLYVLVEYASKGNLREYLRARRppgmdysfdtcklpeEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 465 RNVLLVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMK 544
Cdd:cd05100 163 RNVLVTEDNVMKIADFGLARDVHNID-YYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIP 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 31455611 545 GPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05100 242 VEELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTF 283
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
325-595 6.48e-44

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 158.64  E-value: 6.48e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 325 LKDKKLFLKRdnlliadiELGCGNFGSVRQG-VYRMR--KKQIDVAIKVLKQGTEKAdTEEMMREAQIMHQLDNPYIVRL 401
Cdd:cd05094   2 IKRRDIVLKR--------ELGEGAFGKVFLAeCYNLSptKDKMLVAVKTLKDPTLAA-RKDFQREAELLTNLQHDHIVKF 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 402 IGVC-QAEALMLVMEMAGGGPLHKFL---------------VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAAR 465
Cdd:cd05094  73 YGVCgDGDPLIMVFEYMKHGDLNKFLrahgpdamilvdgqpRQAKGELGLSQMLHIATQIASGMVYLASQHFVHRDLATR 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 466 NVLLVNRHYAKISDFGLSKALGADDsYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKG 545
Cdd:cd05094 153 NCLVGANLLVKIGDFGMSRDVYSTD-YYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSN 231
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 546 PEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd05094 232 TEVIECITQGRVLERPRVCPKEVYDIMLGCWQREPQQRLNIKEIYKILHA 281
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
344-586 1.64e-43

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 157.85  E-value: 1.64e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQL-DNPYIVRLIGVCQAEA-LMLVMEMAGGGP 421
Cdd:cd05088  15 IGEGNFGQVLKARIKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGyLYLAIEYAPHGN 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKR--EEIPVSNVA----------ELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAl 486
Cdd:cd05088  95 LLDFLRKSRvlETDPAFAIAnstastlssqQLLHfaaDVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG- 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 gadDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPP 566
Cdd:cd05088 174 ---QEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDD 250
                       250       260
                ....*....|....*....|
gi 31455611 567 ELYALMSDCWIYKWEDRPDF 586
Cdd:cd05088 251 EVYDLMRQCWREKPYERPSF 270
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
344-592 6.76e-43

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 154.92  E-value: 6.76e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKAD-TEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGGP 421
Cdd:cd13978   1 LGSGGFGTVSKA--RHVSWFGMVAIKCLHSSPNCIEeRKALLKEAEKMERARHSYVLPLLGVCVeRRSLGLVMEYMENGS 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLE--EKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAG 499
Cdd:cd13978  79 LKSLLEREIQDVPWSLRFRIIHEIALGMNFLHnmDPPLLHHDLKPENILLDNHFHVKISDFGLSKLGMKSISANRRRGTE 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KW--PLKWYAPECIN--FRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEV-MAFIEQGKRMECPPEC-------PPE 567
Cdd:cd13978 159 NLggTPIYMAPEAFDdfNKKPTSKSDVYSFAIVIWAVLT-RKEPFENAINPLLiMQIVSKGDRPSLDDIGrlkqienVQE 237
                       250       260
                ....*....|....*....|....*
gi 31455611 568 LYALMSDCWIYKWEDRPDFLTVEQR 592
Cdd:cd13978 238 LISLMIRCWDGNPDARPTFLECLDR 262
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
344-595 7.81e-42

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 152.06  E-value: 7.81e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRkkqiDVAIKVLKQGTEK---ADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd14148   2 IGVGGFGKVYKGLWRGE----EVAVKAARQDPDEdiaVTAENVRQEARLFWMLQHPNIIALRGVCLNPPhLCLVMEYARG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKReeIPVSNVAELLHQVSMGMKYLEEKNFV---HRDLAARNVLLVNR--------HYAKISDFGLSKalga 488
Cdd:cd14148  78 GALNRALAGKK--VPPHVLVNWAVQIARGMNYLHNEAIVpiiHRDLKSSNILILEPienddlsgKTLKITDFGLAR---- 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 489 dDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK-RMECPPECPPE 567
Cdd:cd14148 152 -EWHKTTKMSAAGTYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAMNKlTLPIPSTCPEP 229
                       250       260
                ....*....|....*....|....*...
gi 31455611 568 LYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd14148 230 FARLLEECWDPDPHGRPDFGSILKRLED 257
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
321-591 4.56e-41

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 153.08  E-value: 4.56e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 321 DPEELK-DKKLFLKRDNLLIADIeLGCGNFGSVRQGV-YRMRKKQ--IDVAIKVLKQGTEKADTEEMMREAQIMHQLDN- 395
Cdd:cd05106  23 DPTQLPyNEKWEFPRDNLQFGKT-LGAGAFGKVVEATaFGLGKEDnvLRVAVKMLKASAHTDEREALMSELKILSHLGQh 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 396 PYIVRLIGVC-QAEALMLVMEMAGGGPLHKFLVGKREEI----------------------------------------- 433
Cdd:cd05106 102 KNIVNLLGACtHGGPVLVITEYCCYGDLLNFLRKKAETFlnfvmalpeisetssdyknitlekkyirsdsgfssqgsdty 181
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 434 ----PVS---------------------NVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKA 485
Cdd:cd05106 182 vemrPVSssssqssdskdeedtedswplDLDDLLRfssQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARD 261
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 486 LgADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMK-GPEVMAFIEQGKRMECPPEC 564
Cdd:cd05106 262 I-MNDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILvNSKFYKMVKRGYQMSRPDFA 340
                       330       340
                ....*....|....*....|....*..
gi 31455611 565 PPELYALMSDCWIYKWEDRPDFLTVEQ 591
Cdd:cd05106 341 PPEIYSIMKMCWNLEPTERPTFSQISQ 367
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
344-593 9.17e-41

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 148.74  E-value: 9.17e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmrkkQIDVAIKVLKQGTEKadtEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPL 422
Cdd:cd14058   1 VGRGSFGVVCKARWR----NQIVAVKIIESESEK---KAFEVEVRQLSRVDHPNIIKLYGACsNQKPVCLVMEYAEGGSL 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKrEEIPVSNVAELLH---QVSMGMKYL---EEKNFVHRDLAARNVLLVNRHYA-KISDFGLSkalgADDSYYTA 495
Cdd:cd14058  74 YNVLHGK-EPKPIYTAAHAMSwalQCAKGVAYLhsmKPKALIHRDLKPPNLLLTNGGTVlKICDFGTA----CDISTHMT 148
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYgQKPYKKMKGP--EVMAFIEQGKRmecPP---ECPPELYA 570
Cdd:cd14058 149 NNKGS--AAWMAPEVFEGSKYSEKCDVFSWGIILWEVITR-RKPFDHIGGPafRIMWAVHNGER---PPlikNCPKPIES 222
                       250       260
                ....*....|....*....|...
gi 31455611 571 LMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd14058 223 LMTRCWSKDPEKRPSMKEIVKIM 245
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
344-595 1.01e-40

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 149.42  E-value: 1.01e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRkkqiDVAIKVLKQGTE---KADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd14146   2 IGVGGFGKVYRATWKGQ----EVAVKAARQDPDediKATAESVRQEAKLFSMLRHPNIIKLEGVCLEEPnLCLVMEFARG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVG--------KREEIPVSNVAELLHQVSMGMKYLEEKNFV---HRDLAARNVLL--------VNRHYAKISDF 480
Cdd:cd14146  78 GTLNRALAAanaapgprRARRIPPHILVNWAVQIARGMLYLHEEAVVpilHRDLKSSNILLlekiehddICNKTLKITDF 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 481 GLSKalgadDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK-RME 559
Cdd:cd14146 158 GLAR-----EWHRTTKMSAAGTYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGVAVNKlTLP 231
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 31455611 560 CPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd14146 232 IPSTCPEPFAKLMKECWEQDPHIRPSFALILEQLTA 267
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
344-593 5.10e-40

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 149.38  E-value: 5.10e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQID---VAIKVLKQGTEKADTEEMMREAQIM----HQLDnpyIVRLIGVC--QAEALMLVM 414
Cdd:cd14207  15 LGRGAFGKVVQASAFGIKKSPTcrvVAVKMLKEGATASEYKALMTELKILihigHHLN---VVNLLGACtkSGGPLMVIV 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLVGKR-----------------------------------------------EEIPVSNVAE------- 440
Cdd:cd14207  92 EYCKYGNLSNYLKSKRdffvtnkdtslqeelikekkeaeptggkkkrlesvtssesfassgfqEDKSLSDVEEeeedsgd 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 441 ----------LLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYyTARSAGKWPLKWYA 507
Cdd:cd14207 172 fykrpltmedLISysfQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPDY-VRKGDARLPLKWMA 250
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 508 PECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPE-VMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd14207 251 PESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQIDEdFCSKLKEGIRMRAPEFATSEIYQIMLDCWQGDPNERPRF 330

                ....*..
gi 31455611 587 LTVEQRM 593
Cdd:cd14207 331 SELVERL 337
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
344-589 5.86e-40

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 147.11  E-value: 5.86e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDVAIKVLKQGTEK--ADTEEMMR-EAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd14145  14 IGIGGFGKV----YRAIWIGDEVAVKAARHDPDEdiSQTIENVRqEAKLFAMLKHPNIIALRGVCLKEPnLCLVMEFARG 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKReeIPVSNVAELLHQVSMGMKYLEEKNFV---HRDLAARNVLLVNR--------HYAKISDFGLSKalga 488
Cdd:cd14145  90 GPLNRVLSGKR--IPPDILVNWAVQIARGMNYLHCEAIVpviHRDLKSSNILILEKvengdlsnKILKITDFGLAR---- 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 489 dDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK-RMECPPECPPE 567
Cdd:cd14145 164 -EWHRTTKMSAAGTYAWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYGVAMNKlSLPIPSTCPEP 241
                       250       260
                ....*....|....*....|..
gi 31455611 568 LYALMSDCWIYKWEDRPDFLTV 589
Cdd:cd14145 242 FARLMEDCWNPDPHSRPPFTNI 263
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
344-595 1.21e-38

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 143.63  E-value: 1.21e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKkqidVAIKVLKQGTEK---ADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd14147  11 IGIGGFGKVYRGSWRGEL----VAVKAARQDPDEdisVTAESVRQEARLFAMLAHPNIIALKAVCLEEPnLCLVMEYAAG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKReeIPVSNVAELLHQVSMGMKYLEEKNFV---HRDLAARNVLL--------VNRHYAKISDFGLSKalga 488
Cdd:cd14147  87 GPLSRALAGRR--VPPHVLVNWAVQIARGMHYLHCEALVpviHRDLKSNNILLlqpienddMEHKTLKITDFGLAR---- 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 489 dDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK-RMECPPECPPE 567
Cdd:cd14147 161 -EWHKTTQMSAAGTYAWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAVNKlTLPIPSTCPEP 238
                       250       260
                ....*....|....*....|....*...
gi 31455611 568 LYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd14147 239 FAQLMADCWAQDPHRRPDFASILQQLEA 266
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
343-584 3.21e-38

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 141.96  E-value: 3.21e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKADT--EEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMA 417
Cdd:cd14014   7 LLGRGGMGEV----YRARDTLLGrpVAIKVLRPELAEDEEfrERFLREARALARLSHPNIVRVYDVGEDDGRPyIVMEYV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd14014  83 EGGSLADLL-RERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSV 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 AGKWPlkwY-APECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRM---ECPPECPPELYALMS 573
Cdd:cd14014 162 LGTPA---YmAPEQARGGPVDPRSDIYSLGVVLYELLT-GRPPFDGDSPAAVLAKHLQEAPPppsPLNPDVPPALDAIIL 237
                       250
                ....*....|.
gi 31455611 574 DCWIYKWEDRP 584
Cdd:cd14014 238 RALAKDPEERP 248
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
334-593 2.24e-37

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 142.04  E-value: 2.24e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 334 RDNLLIADiELGCGNFGSVRQG-VYRMRKKQI--DVAIKVLKQGTEKADTEEMMREAQIM----HQLDnpyIVRLIGVCQ 406
Cdd:cd05103   6 RDRLKLGK-PLGRGAFGQVIEAdAFGIDKTATcrTVAVKMLKEGATHSEHRALMSELKILihigHHLN---VVNLLGACT 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 407 AEA--LMLVMEMAGGGPLHKFLVGKR----------------------------------------------EEIPVSNV 438
Cdd:cd05103  82 KPGgpLMVIVEFCKFGNLSAYLRSKRsefvpyktkgarfrqgkdyvgdisvdlkrrldsitssqssassgfvEEKSLSDV 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 439 AE--------------LLH------QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSA 498
Cdd:cd05103 162 EEeeagqedlykdfltLEDlicysfQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGDA 241
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 499 gKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMK-GPEVMAFIEQGKRMECPPECPPELYALMSDCWI 577
Cdd:cd05103 242 -RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 320
                       330
                ....*....|....*.
gi 31455611 578 YKWEDRPDFLTVEQRM 593
Cdd:cd05103 321 GEPSQRPTFSELVEHL 336
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
319-593 4.22e-37

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 141.97  E-value: 4.22e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 319 YSDPEELK-DKKLFLKRDNLLIADIeLGCGNFGSVRQGV-YRMRKKQ--IDVAIKVLKQGTEKADTEEMMREAQIMHQLD 394
Cdd:cd05104  18 YIDPTQLPyDHKWEFPRDRLRFGKT-LGAGAFGKVVEATaYGLAKADsaMTVAVKMLKPSAHSTEREALMSELKVLSYLG 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 395 NPY-IVRLIGVCQAEALMLVM-EMAGGGPLHKFLVGKRE----------------------------------------- 431
Cdd:cd05104  97 NHInIVNLLGACTVGGPTLVItEYCCYGDLLNFLRRKRDsficpkfedlaeaalyrnllhqremacdslneymdmkpsvs 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 432 -------------------------EIP--------VSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKIS 478
Cdd:cd05104 177 yvvptkadkrrgvrsgsyvdqdvtsEILeedelaldTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKIC 256
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 479 DFGLSKALgADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMK-GPEVMAFIEQGKR 557
Cdd:cd05104 257 DFGLARDI-RNDSNYVVKGNARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPvDSKFYKMIKEGYR 335
                       330       340       350
                ....*....|....*....|....*....|....*.
gi 31455611 558 MECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd05104 336 MDSPEFAPSEMYDIMRSCWDADPLKRPTFKQIVQLI 371
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
315-586 4.34e-37

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 142.84  E-value: 4.34e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 315 YESPYSDPEELK-DKKLFLKRDNLLIADIeLGCGNFGSVRQGV---YRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIM 390
Cdd:cd05107  16 HEYIYVDPMQLPyDSAWEMPRDNLVLGRT-LGSGAFGRVVEATahgLSHSQSTMKVAVKMLKSTARSSEKQALMSELKIM 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 391 HQLdNPY--IVRLIGVC-QAEALMLVMEMAGGGPL--------HKFL--------------------------------- 426
Cdd:cd05107  95 SHL-GPHlnIVNLLGACtKGGPIYIITEYCRYGDLvdylhrnkHTFLqyyldknrddgslisggstplsqrkshvslgse 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 427 -------VGKRE----------------------------------------------EIPVSNVAELL---HQVSMGMK 450
Cdd:cd05107 174 sdggymdMSKDEsadyvpmqdmkgtvkyadiessnyespydqylpsapertrrdtlinESPALSYMDLVgfsYQVANGME 253
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 451 YLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMW 530
Cdd:cd05107 254 FLASKNCVHRDLAARNVLICEGKLVKICDFGLARDI-MRDSNYISKGSTFLPLKWMAPESIFNNLYTTLSDVWSFGILLW 332
                       330       340       350       360       370
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 531 EALSYGQKPYKKMKGPEVM-AFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05107 333 EIFTLGGTPYPELPMNEQFyNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDF 389
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
334-586 4.54e-37

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 140.88  E-value: 4.54e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 334 RDNLLIADIeLGCGNFGSVRQG-VYRMRKKQI--DVAIKVLKQGTEKADTEEMMREAQIMHQLDNPY-IVRLIGVCQAE- 408
Cdd:cd05102   6 RDRLRLGKV-LGHGAFGKVVEAsAFGIDKSSSceTVAVKMLKEGATASEHKALMSELKILIHIGNHLnVVNLLGACTKPn 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 409 -ALMLVMEMAGGGPLHKFLVGKRE------------EIPVSNVAELLH-------------------------------- 443
Cdd:cd05102  85 gPLMVIVEFCKYGNLSNFLRAKREgfspyrersprtRSQVRSMVEAVRadrrsrqgsdrvasftestsstnqprqevddl 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 444 ---------------QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAgKWPLKWYAP 508
Cdd:cd05102 165 wqspltmedlicysfQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGSA-RLPLKWMAP 243
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 509 ECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMK-GPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05102 244 ESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQiNEEFCQRLKDGTRMRAPEYATPEIYRIMLSCWHGDPKERPTF 322
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
315-587 2.33e-36

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 140.54  E-value: 2.33e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 315 YESPYSDPEELK-DKKLFLKRDNLLIADIeLGCGNFGSVRQGV-YRMRKKQ--IDVAIKVLKQGTEKADTEEMMREAQIM 390
Cdd:cd05105  16 HEYIYVDPMQLPyDSRWEFPRDGLVLGRI-LGSGAFGKVVEGTaYGLSRSQpvMKVAVKMLKPTARSSEKQALMSELKIM 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 391 HQLdNPY--IVRLIGVC-QAEALMLVMEMAGGGPLHKFLVGKREEI---------------------------------- 433
Cdd:cd05105  95 THL-GPHlnIVNLLGACtKSGPIYIITEYCFYGDLVNYLHKNRDNFlsrhpekpkkdldifginpadestrsyvilsfen 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 434 --------------------------------------------PVSNVAELL-----------------HQVSMGMKYL 452
Cdd:cd05105 174 kgdymdmkqadttqyvpmleikeaskysdiqrsnydrpasykgsNDSEVKNLLsddgseglttldllsftYQVARGMEFL 253
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 453 EEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEA 532
Cdd:cd05105 254 ASKNCVHRDLAARNVLLAQGKIVKICDFGLARDI-MHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEI 332
                       330       340       350       360       370
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611 533 LSYGQKPYKKMK-GPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFL 587
Cdd:cd05105 333 FSLGGTPYPGMIvDSTFYNKIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFL 388
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
344-589 5.76e-36

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 135.69  E-value: 5.76e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYR----MRKKQIDVAIKVLKQGTEKADtEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGG 419
Cdd:cd05037   7 LGQGTFTNIYDGILRevgdGRVQEVEVLLKVLDSDHRDIS-ESFFETASLMSQISHKHLVKLYGVCVADENIMVQEYVRY 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV------NRHYAKISDFGLSKALGADDsYY 493
Cdd:cd05037  86 GPLDKYLRRMGNNVPLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNILLAregldgYPPFIKLSDPGVPITVLSRE-ER 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 494 TARSAgkwplkWYAPECIN--FRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECpPECpPELYAL 571
Cdd:cd05037 165 VDRIP------WIAPECLRnlQANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPA-PDC-AELAEL 236
                       250
                ....*....|....*...
gi 31455611 572 MSDCWIYKWEDRPDFLTV 589
Cdd:cd05037 237 IMQCWTYEPTKRPSFRAI 254
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
342-594 1.17e-35

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 134.64  E-value: 1.17e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGvyRMRKKQIDVAIKVLKQgTEKADTEEMMREAQIMHQLDNPYIVRLIG-VCQAEALMLVMEMAGGG 420
Cdd:cd05122   6 EKIGKGGFGVVYKA--RHKKTGQIVAIKKINL-ESKEKKESILNEIAILKKCKHPNIVKYYGsYLKKDELWIVMEFCSGG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL---GADDSYYTARS 497
Cdd:cd05122  83 SLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLsdgKTRNTFVGTPY 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 agkwplkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQG--KRMECPPECPPELYALMSDC 575
Cdd:cd05122 163 -------WMAPEVIQGKPYGFKADIWSLGITAIE-MAEGKPPYSELPPMKALFLIATNgpPGLRNPKKWSKEFKDFLKKC 234
                       250
                ....*....|....*....
gi 31455611 576 WIYKWEDRPdflTVEQRMR 594
Cdd:cd05122 235 LQKDPEKRP---TAEQLLK 250
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
344-586 2.59e-35

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 133.39  E-value: 2.59e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKkqidVAIKVLKqgtEKADTEemmreaqIMH--QLDNPYIVRLIGVC-QAEALMLVMEMAGGG 420
Cdd:cd14059   1 LGSGAQGAVFLGKFRGEE----VAVKKVR---DEKETD-------IKHlrKLNHPNIIKFKGVCtQAPCYCILMEYCPYG 66
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArsAGK 500
Cdd:cd14059  67 QLYEVLRAGRE-ITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKELSEKSTKMSF--AGT 143
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 wpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFI-EQGKRMECPPECPPELYALMSDCWIYK 579
Cdd:cd14059 144 --VAWMAPEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIIWGVgSNSLQLPVPSTCPDGFKLLMKQCWNSK 220

                ....*..
gi 31455611 580 WEDRPDF 586
Cdd:cd14059 221 PRNRPSF 227
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
343-571 6.11e-35

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 138.22  E-value: 6.11e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKVLKQgtEKADTEEMM----REAQIMHQLDNPYIVRLIGVCQAEALM-LVME 415
Cdd:COG0515  14 LLGRGGMGVV----YLARDLRLGrpVALKVLRP--ELAADPEARerfrREARALARLNHPNIVRVYDVGEEDGRPyLVME 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:COG0515  88 YVEGESLAD-LLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTG 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWPlkwY-APECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRM---ECPPECPPELYAL 571
Cdd:COG0515 167 TVVGTPG---YmAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPppsELRPDLPPALDAI 242
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
159-255 3.46e-34

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 125.39  E-value: 3.46e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEY 238
Cdd:cd10401   1 EKMPWFHGKISREESEQILLIGSKTNGKFLIRERDNNGSYALCLLHDGKVLHYRIDKDKTGKLSIPDGKKFDTLWQLVEH 80
                        90
                ....*....|....*..
gi 31455611 239 LKLKADGLIYCLKEACP 255
Cdd:cd10401  81 YSYKPDGLLRVLTEPCP 97
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
344-573 1.25e-33

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 128.79  E-value: 1.25e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGP 421
Cdd:cd14003   8 LGEGSFGKVKLARHKLTGEK--VAIKIIDKSKLKEEIEEKiKREIEIMKLLNHPNIIKLYEVIETEnKIYLVMEYASGGE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTarSAGKW 501
Cdd:cd14003  86 LFDYIV-NNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGGSLLKT--FCGTP 162
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 502 PlkwY-APECINFRKF-SSRSDVWSYGVTMWeALSYGQKPYkkmKGPEVMAF---IEQGKrMECPPECPPELYALMS 573
Cdd:cd14003 163 A---YaAPEVLLGRKYdGPKADVWSLGVILY-AMLTGYLPF---DDDNDSKLfrkILKGK-YPIPSHLSPDARDLIR 231
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
344-591 3.98e-33

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 127.64  E-value: 3.98e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIK-VLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGP 421
Cdd:cd06606   8 LGKGSFGSVYLALNLDTGELM--AVKeVELSGDSEEELEALEREIRILSSLKHPNIVRYLGTERTEnTLNIFLEYVPGGS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFL--VGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS-A 498
Cdd:cd06606  86 LASLLkkFGKLPE---PVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIATGEGTKSlR 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 499 GKwPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGP-EVMAFIeqGKRMECP--PEC-PPELYALMSD 574
Cdd:cd06606 163 GT-PY-WMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPWSELGNPvAALFKI--GSSGEPPpiPEHlSEEAKDFLRK 237
                       250
                ....*....|....*..
gi 31455611 575 CWIYKWEDRPdflTVEQ 591
Cdd:cd06606 238 CLQRDPKKRP---TADE 251
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
345-586 4.21e-32

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 124.30  E-value: 4.21e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 345 GCGNFGSVRQGVYRMRKKQidVAIKVLKQgtekadteeMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPLH 423
Cdd:cd14060   2 GGGSFGSVYRAIWVSQDKE--VAVKKLLK---------IEKEAEILSVLSHRNIIQFYGAIlEAPNYGIVTEYASYGSLF 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 424 KFLVGKR-EEIPVSNVAELLHQVSMGMKYLEEK---NFVHRDLAARNVLLVNRHYAKISDFGLSKALGaddsYYTARS-A 498
Cdd:cd14060  71 DYLNSNEsEEMDMDQIMTWATDIAKGMHYLHMEapvKVIHRDLKSRNVVIAADGVLKICDFGASRFHS----HTTHMSlV 146
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 499 GKWPlkWYAPECINFRKFSSRSDVWSYGVTMWEALSYgQKPYKKMKGPEVM-AFIEQGKRMECPPECPPELYALMSDCWI 577
Cdd:cd14060 147 GTFP--WMAPEVIQSLPVSETCDTYSYGVVLWEMLTR-EVPFKGLEGLQVAwLVVEKNERPTIPSSCPRSFAELMRRCWE 223

                ....*....
gi 31455611 578 YKWEDRPDF 586
Cdd:cd14060 224 ADVKERPSF 232
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
343-585 4.43e-31

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 121.95  E-value: 4.43e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVyRMRKKQIdVAIKVLK-QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGG 420
Cdd:cd06627   7 LIGRGAFGSVYKGL-NLNTGEF-VAIKQISlEKIPKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKtKDSLYIILEYVENG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyYTARSAGK 500
Cdd:cd06627  85 SLAS-IIKKFGKFPESLVAVYIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVATKLNEVEK-DENSVVGT 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 wPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd06627 163 -PY-WMAPEVIEMSGVTTASDIWSVGCTVIELLT-GNPPYYDLQPMAALFRIVQDDHPPLPENISPELRDFLLQCFQKDP 239

                ....*
gi 31455611 581 EDRPD 585
Cdd:cd06627 240 TLRPS 244
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
343-585 2.71e-30

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 119.49  E-value: 2.71e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKV--LKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMA 417
Cdd:cd08215   7 VIGKGSFGSA----YLVRRKSDGklYVLKEidLSNMSEK-EREEALNEVKLLSKLKHPNIVKYYESFEENgKLCIVMEYA 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFL---VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYyt 494
Cdd:cd08215  82 DGGDLAQKIkkqKKKGQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKVLESTTDL-- 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 495 ARSAGKWPLkwY-APECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMS 573
Cdd:cd08215 160 AKTVVGTPY--YlSPELCENKPYNYKSDIWALGCVLYE-LCTLKHPFEANNLPALVYKIVKGQYPPIPSQYSSELRDLVN 236
                       250
                ....*....|..
gi 31455611 574 DCWIYKWEDRPD 585
Cdd:cd08215 237 SMLQKDPEKRPS 248
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
344-562 3.89e-30

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 118.93  E-value: 3.89e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdVAIK-VLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAGGGP 421
Cdd:cd14121   3 LGSGTYATVYKAYRKSGAREV-VAVKcVSKSSLNKASTENLLTEIELLKKLKHPHIVELKDFqWDEEHIYLIMEYCSGGD 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFlVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA--KISDFGLSKALGADDSYYTARSAg 499
Cdd:cd14121  82 LSRF-IRSRRTLPESTVRRFLQQLASALQFLREHNISHMDLKPQNLLLSSRYNPvlKLADFGFAQHLKPNDEAHSLRGS- 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611 500 kwPLkWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMAFIEQGKRMECPP 562
Cdd:cd14121 160 --PL-YMAPEMILKKKYDARVDLWSVGVILYECL-FGRAPFASRSFEELEEKIRSSKPIEIPT 218
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
343-529 7.98e-30

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 118.35  E-value: 7.98e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVL-KQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGG 420
Cdd:cd05117   7 VLGRGSFGVVRLAVHKKTGEE--YAVKIIdKKKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEdDKNLYLVMELCTGG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA---KISDFGLSKALGADDSYYTArs 497
Cdd:cd05117  85 ELFDRIV-KKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDspiKIIDFGLAKIFEEGEKLKTV-- 161
                       170       180       190
                ....*....|....*....|....*....|...
gi 31455611 498 AGKwPLkwY-APECINFRKFSSRSDVWSYGVTM 529
Cdd:cd05117 162 CGT-PY--YvAPEVLKGKGYGKKCDIWSLGVIL 191
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
343-577 2.58e-29

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 117.36  E-value: 2.58e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd14206   4 EIGNGWFGKVILGEIFSDYTPAQVVVKELRVSAGPLEQRKFISEAQPYRSLQHPNILQCLGLCtETIPFLLIMEFCQLGD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKRE------EIP---VSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSY 492
Cdd:cd14206  84 LKRYLRAQRKadgmtpDLPtrdLRTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSHNNYKEDYY 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAgkW-PLKWYAPECIN-------FRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECppeC 564
Cdd:cd14206 164 LTPDRL--WiPLRWVAPELLDelhgnliVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVVREQQMKL---A 238
                       250       260
                ....*....|....*....|.
gi 31455611 565 PPEL--------YALMSDCWI 577
Cdd:cd14206 239 KPRLklpyadywYEIMQSCWL 259
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
344-568 2.93e-29

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 116.88  E-value: 2.93e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyrmRKKQID--VAIKVLK-------------QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC--- 405
Cdd:cd14008   1 LGRGSFGKVKLA----LDTETGqlYAIKIFNksrlrkrregkndRGKIKNALDDVRREIAIMKKLDHPNIVRLYEVIddp 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 406 QAEALMLVMEMAGGGPLHKFLVGKR-EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK 484
Cdd:cd14008  77 ESDKLYLVLEYCEGGPVMELDSGDRvPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSE 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 485 ALGADDSyYTARSAGKwPLkWYAPEC--INFRKFSSR-SDVWSYGVTMWeALSYGQKPYKKMKGPEVMAFIEQGKRM-EC 560
Cdd:cd14008 157 MFEDGND-TLQKTAGT-PA-FLAPELcdGDSKTYSGKaADIWALGVTLY-CLVFGRLPFNGDNILELYEAIQNQNDEfPI 232

                ....*...
gi 31455611 561 PPECPPEL 568
Cdd:cd14008 233 PPELSPEL 240
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
343-585 3.31e-28

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 113.84  E-value: 3.31e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAGGGP 421
Cdd:cd06623   8 VLGQGSSGVVYKVRHKPTGKI--YALKKIHVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAfYKEGEISIVLEYMDGGS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKfLVGKREEIPVSNVAELLHQVSMGMKYL-EEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL----GADDSY---Y 493
Cdd:cd06623  86 LAD-LLKKVGKIPEPVLAYIARQILKGLDYLhTKRHIIHRDIKPSNLLINSKGEVKIADFGISKVLentlDQCNTFvgtV 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 494 TARSagkwplkwyaPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQgKRMECPPECP-----PEL 568
Cdd:cd06623 165 TYMS----------PERIQGESYSYAADIWSLGLTLLE-CALGKFPFLPPGQPSFFELMQA-ICDGPPPSLPaeefsPEF 232
                       250
                ....*....|....*..
gi 31455611 569 YALMSDCWIYKWEDRPD 585
Cdd:cd06623 233 RDFISACLQKDPKKRPS 249
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
343-584 3.83e-28

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 113.93  E-value: 3.83e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd05087   4 EIGHGWFGKVFLGEVNSGLSSTQVVVKELKASASVQDQMQFLEEAQPYRALQHTNLLQCLAQCaEVTPYLLVMEFCPLGD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQ----VSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd05087  84 LKGYLRSCRAAESMAPDPLTLQRmaceVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCKYKEDYFVTADQ 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 agKW-PLKWYAPECIN-------FRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECP-PECPPEL 568
Cdd:cd05087 164 --LWvPLRWIAPELVDevhgnllVVDQTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLTYTVREQQLKLPkPQLKLSL 241
                       250       260
                ....*....|....*....|
gi 31455611 569 ----YALMSDCWIyKWEDRP 584
Cdd:cd05087 242 aerwYEVMQFCWL-QPEQRP 260
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
344-593 5.08e-28

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 112.97  E-value: 5.08e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKqidvaIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14065   1 LGKGFFGEVYKVTHRETGK-----VMVMKELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNkLNFITEYVNGGTL 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL--VNR-HYAKISDFGLSKALGaddSYYTARSAG 499
Cdd:cd14065  76 EELLKSMDEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVreANRgRNAVVADFGLAREMP---DEKTKKPDR 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPLK------WYAPECINFRKFSSRSDVWSYGVTMWEALsyGQKPYKKMKGPEVMAF--IEQGKRMECPPECPPELYAL 571
Cdd:cd14065 153 KKRLTvvgspyWMAPEMLRGESYDEKVDVFSFGIVLCEII--GRVPADPDYLPRTMDFglDVRAFRTLYVPDCPPSFLPL 230
                       250       260
                ....*....|....*....|..
gi 31455611 572 MSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd14065 231 AIRCCQLDPEKRPSFVELEHHL 252
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
343-585 9.80e-28

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 112.44  E-value: 9.80e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgvYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGP 421
Cdd:cd06605   8 ELGEGNGGVVSK--VRHRPSGQIMAVKVIRLEIDEALQKQILRELDVLHKCNSPYIVGFYGAFYSEgDISICMEYMDGGS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLvgKR-EEIPVSNVAELLHQVSMGMKYLEEK-NFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYYTarSAG 499
Cdd:cd06605  86 LDKIL--KEvGRIPERILGKIAVAVVKGLIYLHEKhKIIHRDVKPSNILVNSRGQVKLCDFGVSGQL-VDSLAKT--FVG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPlkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQgkrMEC-----PPECP-----PELY 569
Cdd:cd06605 161 TRS--YMAPERISGGKYTVKSDIWSLGLSLVE-LATGRFPYPPPNAKPSMMIFEL---LSYivdepPPLLPsgkfsPDFQ 234
                       250
                ....*....|....*.
gi 31455611 570 ALMSDCWIYKWEDRPD 585
Cdd:cd06605 235 DFVSQCLQKDPTERPS 250
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
344-584 2.57e-27

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 111.20  E-value: 2.57e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQgteKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGPL 422
Cdd:cd06612  11 LGEGSYGSVYKAIHKETGQV--VAIKVVPV---EEDLQEIIKEISILKQCDSPYIVKYYGSYFKNtDLWIVMEYCGAGSV 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGadDSYYTARSAGKWP 502
Cdd:cd06612  86 SDIMKITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLT--DTMAKRNTVIGTP 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 503 LkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQG--KRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd06612 164 F-WMAPEVIQEIGYNNKADIWSLGITAIE-MAEGKPPYSDIHPMRAIFMIPNKppPTLSDPEKWSPEFNDFVKKCLVKDP 241

                ....
gi 31455611 581 EDRP 584
Cdd:cd06612 242 EERP 245
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
343-584 3.59e-27

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 111.14  E-value: 3.59e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCqAEAL--MLVMEMAGGG 420
Cdd:cd05042   2 EIGNGWFGKVLLGEIYSGTSVAQVVVKELKASANPKEQDTFLKEGQPYRILQHPNILQCLGQC-VEAIpyLLVMEFCDLG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKRE-EIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTAR 496
Cdd:cd05042  81 DLKAYLRSEREhERGDSDTRTLQRmacEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAHSRYKEDYIETDD 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 497 SagKW-PLKWYAPECINfrKFSSR---------SDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPpecPP 566
Cdd:cd05042 161 K--LWfPLRWTAPELVT--EFHDRllvvdqtkySNIWSLGVTLWELFENGAQPYSNLSDLDVLAQVVREQDTKLP---KP 233
                       250       260
                ....*....|....*....|....*.
gi 31455611 567 EL--------YALMSDCWIYKwEDRP 584
Cdd:cd05042 234 QLelpysdrwYEVLQFCWLSP-EQRP 258
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
344-596 4.34e-27

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 110.31  E-value: 4.34e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKkqidVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVC--QAEALMLVMEMAGG 419
Cdd:cd14064   1 IGSGSFGKVYKGRCRNKI----VAIKRYRANTycSKSDVDMFCREVSILCRLNHPCVIQFVGACldDPSQFAIVTQYVSG 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEE--KNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd14064  77 GSLFSLLHEQKRVIDLQSKLIIAVDVAKGMEYLHNltQPIIHRDLNSHNILLYEDGHAVVADFGESRFLQSLDEDNMTKQ 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 AGKwpLKWYAPECIN-FRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAfiEQGKRMECPP---ECPPELYALMS 573
Cdd:cd14064 157 PGN--LRWMAPEVFTqCTRYSIKADVFSYALCLWELLT-GEIPFAHLKPAAAAA--DMAYHHIRPPigySIPKPISSLLM 231
                       250       260
                ....*....|....*....|...
gi 31455611 574 DCWIYKWEDRPDFLTVEQRMRAC 596
Cdd:cd14064 232 RGWNAEPESRPSFVEIVALLEPC 254
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
381-598 1.16e-26

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 109.51  E-value: 1.16e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 381 EEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVH 459
Cdd:cd14027  36 EALLEEGKMMNRLRHSRVVKLLGVILEEGkYSLVMEYMEKGNLMHVL--KKVSVPLSVKGRIILEIIEGMAYLHGKGVIH 113
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 460 RDLAARNVLLVNRHYAKISDFGL-------------SKALGADDSYYtARSAGKwpLKWYAPECIN--FRKFSSRSDVWS 524
Cdd:cd14027 114 KDLKPENILVDNDFHIKIADLGLasfkmwskltkeeHNEQREVDGTA-KKNAGT--LYYMAPEHLNdvNAKPTEKSDVYS 190
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 525 YGVTMWeALSYGQKPYKKMKGPEVMAF-IEQGKR---MECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRACYY 598
Cdd:cd14027 191 FAIVLW-AIFANKEPYENAINEDQIIMcIKSGNRpdvDDITEYCPREIIDLMKLCWEANPEARPTFPGIEEKFRPFYL 267
Pkinase pfam00069
Protein kinase domain;
343-584 3.47e-26

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 106.56  E-value: 3.47e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   343 ELGCGNFGSVRQGVYRMRKKqiDVAIKVLKQGTEKADTEE-MMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:pfam00069   6 KLGSGSFGTVYKAKHRDTGK--IVAIKKIKKEKIKKKKDKnILREIKILKKLNHPNIVRLYDAFEDKDnLYLVLEYVEGG 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   421 PLHKFLVgkreeipvsnvaellhqvsmgmkylEEKNFVHRDLaarnvllvnRHYAKisdfGLSKALgADDSYYTARSAGK 500
Cdd:pfam00069  84 SLFDLLS-------------------------EKGAFSEREA---------KFIMK----QILEGL-ESGSSLTTFVGTP 124
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   501 WplkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRM--ECPPECPPELYALMSDCWIY 578
Cdd:pfam00069 125 W---YMAPEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPGINGNEIYELIIDQPYAfpELPSNLSEEAKDLLKKLLKK 200

                  ....*.
gi 31455611   579 KWEDRP 584
Cdd:pfam00069 201 DPSKRL 206
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
338-586 4.15e-26

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 107.73  E-value: 4.15e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 338 LIADIELGCGNFGSVRQGVYRM-----RKKQIDVAIKVLKQgTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALM 411
Cdd:cd05078   1 LIFNESLGQGTFTKIFKGIRREvgdygQLHETEVLLKVLDK-AHRNYSESFFEAASMMSQLSHKHLVLNYGVCVcGDENI 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 412 LVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV--------NRHYAKISDFGLS 483
Cdd:cd05078  80 LVQEYVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEEKTLVHGNVCAKNILLIreedrktgNPPFIKLSDPGIS 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 484 KALGADDSYYTArsagkwpLKWYAPECI-NFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQgkRMECPP 562
Cdd:cd05078 160 ITVLPKDILLER-------IPWVPPECIeNPKNLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYED--RHQLPA 230
                       250       260
                ....*....|....*....|....
gi 31455611 563 ECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05078 231 PKWTELANLINNCMDYEPDHRPSF 254
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
344-575 6.76e-26

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 106.92  E-value: 6.76e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIK-VLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMAGGGP 421
Cdd:cd14009   1 IGRGSFATVWKG--RHKQTGEVVAIKeISRKKLNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIyLVLEYCAGGD 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA---KISDFGLSKALGADDSYYTARSA 498
Cdd:cd14009  79 LSQYI-RKRGRLPEAVARHFMQQLASGLKFLRSKNIIHRDLKPQNLLLSTSGDDpvlKIADFGFARSLQPASMAETLCGS 157
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 499 gkwPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRMECPPECPPelyaLMSDC 575
Cdd:cd14009 158 ---PL-YMAPEILQFQKYDAKADLWSVGAILFEMLV-GKPPFRGSNHVQLLRNIERSDAVIPFPIAAQ----LSPDC 225
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
344-593 8.58e-26

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 106.97  E-value: 8.58e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMR-KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd14066   1 IGSGGFGTV----YKGVlENGTVVAVKRLNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYClESDEKLLVYEYMPNGS 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVS-----NVAEllhQVSMGMKYLEEKNF---VHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYY 493
Cdd:cd14066  77 LEDRLHCHKGSPPLPwpqrlKIAK---GIARGLEYLHEECPppiIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVS 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 494 T----ARSAGkwplkwY-APECINFRKFSSRSDVWSYGVTMWEALSyGQKP----------------YKKMKGPEVMAFI 552
Cdd:cd14066 154 KtsavKGTIG------YlAPEYIRTGRVSTKSDVYSFGVVLLELLT-GKPAvdenrenasrkdlvewVESKGKEELEDIL 226
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 31455611 553 EQ--GKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd14066 227 DKrlVDDDGVEEEEVEALLRLALLCTRSDPSLRPSMKEVVQML 269
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
344-594 9.14e-26

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 106.71  E-value: 9.14e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMrkkqiDVAIKVLKQgteKADTEEMMR----EAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGG 419
Cdd:cd14062   1 IGSGSFGTVYKGRWHG-----DVAVKKLNV---TDPTPSQLQafknEVAVLRKTRHVNILLFMGYMTKPQLAIVTQWCEG 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlgaddsyyTARSAG 499
Cdd:cd14062  73 SSLYKHLHVLETKFEMLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLATV--------KTRWSG 144
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPLK-------WYAPECINFRK---FSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIeQGK------RMECPPE 563
Cdd:cd14062 145 SQQFEqptgsilWMAPEVIRMQDenpYSFQSDVYAFGIVLYELLT-GQLPYSHINNRDQILFM-VGRgylrpdLSKVRSD 222
                       250       260       270
                ....*....|....*....|....*....|.
gi 31455611 564 CPPELYALMSDCWIYKWEDRPDFLTVEQRMR 594
Cdd:cd14062 223 TPKALRRLMEDCIKFQRDERPLFPQILASLE 253
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
343-568 1.43e-25

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 106.56  E-value: 1.43e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmRKKQIdVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIG-VCQAEALMLVME-MAGGG 420
Cdd:cd06609   8 RIGKGSFGEVYKGIDK-RTNQV-VAIKVIDLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGsFLKGSKLWIIMEyCGGGS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGaddSYYTARS--A 498
Cdd:cd06609  86 VLDLLKPGPLDE---TYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSGQLT---STMSKRNtfV 159
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 499 GKwPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIeqgkrmecPPECPPEL 568
Cdd:cd06609 160 GT-PF-WMAPEVIKQSGYDEKADIWSLGITAIE-LAKGEPPLSDLHPMRVLFLI--------PKNNPPSL 218
SH2 pfam00017
SH2 domain;
10-87 1.57e-25

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 99.98  E-value: 1.57e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611    10 FFYGSISRAEAEEHLkLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFY 87
Cdd:pfam00017   1 WYHGKISRQEAERLL-LNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGGYYISGGVKFSSLAELVEHY 77
SH2 pfam00017
SH2 domain;
163-238 1.92e-25

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 99.98  E-value: 1.92e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611   163 WYHSSLTREEAERKLYSGaQTDGKFLLRPR-KEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEY 238
Cdd:pfam00017   1 WYHGKISRQEAERLLLNG-KPDGTFLVRESeSTPGGYTLSVRDDGKVKHYKIQSTDNGGYYISGGVKFSSLAELVEH 76
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
344-602 4.44e-25

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 104.78  E-value: 4.44e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQG--TEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGG 420
Cdd:cd14073   9 LGKGTYGKVKLAIERATGRE--VAIKSIKKDkiEDEQDMVRIRREIEIMSSLNHPHIIRIYEVFENkDKIVIVMEYASGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFlVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAgk 500
Cdd:cd14073  87 ELYDY-ISERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKDKLLQTFCGS-- 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 wPLkwYA-PECINFRKFSS-RSDVWSYGVTMWeALSYGQKP-----YKKMKGPevmafIEQGKRMEcpPECPPELYALMS 573
Cdd:cd14073 164 -PL--YAsPEIVNGTPYQGpEVDCWSLGVLLY-TLVYGTMPfdgsdFKRLVKQ-----ISSGDYRE--PTQPSDASGLIR 232
                       250       260
                ....*....|....*....|....*....
gi 31455611 574 DCwiykwedrpdfLTVEQRMRACYYSLAS 602
Cdd:cd14073 233 WM-----------LTVNPKRRATIEDIAN 250
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
344-595 5.30e-25

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 104.71  E-value: 5.30e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyrmrKKQIDVAIKVLKQGTEKADTEEMMR-EAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGPL 422
Cdd:cd14150   8 IGTGSFGTVFRG-----KWHGDVAVKILKVTEPTPEQLQAFKnEMQVLRKTRHVNILLFMGFMTRPNFAIITQWCEGSSL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlgaddsyyTARSAGKWP 502
Cdd:cd14150  83 YRHLHVTETRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATV--------KTRWSGSQQ 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 503 LK-------WYAPECINFRK---FSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIeQGKRMECP------PECPP 566
Cdd:cd14150 155 VEqpsgsilWMAPEVIRMQDtnpYSFQSDVYAYGVVLYELMS-GTLPYSNINNRDQIIFM-VGRGYLSPdlsklsSNCPK 232
                       250       260       270
                ....*....|....*....|....*....|...
gi 31455611 567 ELYALMSDCWIYKWEDRPDF----LTVEQRMRA 595
Cdd:cd14150 233 AMKRLLIDCLKFKREERPLFpqilVSIELLQRL 265
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
347-587 6.97e-25

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 105.00  E-value: 6.97e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 347 GNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKADTEE--MMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPLH 423
Cdd:cd14026   8 GAFGTVSRA--RHADWRVTVAIKCLKLDSPVGDSERncLLKEAEILHKARFSYILPILGICnEPEFLGIVTEYMTNGSLN 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 424 KFLVGKrEEIPvsNVA-----ELLHQVSMGMKYLEEKN--FVHRDLAARNVLLVNRHYAKISDFGLSK----ALGADDSY 492
Cdd:cd14026  86 ELLHEK-DIYP--DVAwplrlRILYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSKwrqlSISQSRSS 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGK---WPLKWYAPEciNFRKFSSRSDVWSYGVTMWEALSYGQkPYKKMKGP-EVMAFIEQGKRMECPPECPP-- 566
Cdd:cd14026 163 KSAPEGGTiiyMPPEEYEPS--QKRRASVKHDIYSYAIIMWEVLSRKI-PFEEVTNPlQIMYSVSQGHRPDTGEDSLPvd 239
                       250       260
                ....*....|....*....|....*.
gi 31455611 567 -----ELYALMSDCWIYKWEDRPDFL 587
Cdd:cd14026 240 iphraTLINLIESGWAQNPDERPSFL 265
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
343-540 1.87e-24

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 103.23  E-value: 1.87e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKkqidVAIKVLKQGTEKADTEEMMR-EAQIMHqLDNPYIVRLIGVCQAEAL----MLVMEMA 417
Cdd:cd13979  10 PLGSGGFGSVYKATYKGET----VAVKIVRRRRKNRASRQSFWaELNAAR-LRHENIVRVLAAETGTDFaslgLIIMEYC 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd13979  85 GNGTLQQLIYEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEGNEVGTPRS 164
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 498 AGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd13979 165 HIGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLT-RELPY 206
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
356-593 2.46e-24

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 102.55  E-value: 2.46e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 356 VYRMRKKQIDvAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPLHKfLVGKREEIP 434
Cdd:cd14155   9 VYKVRHRTSG-QVMALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVCVHQGqLHALTEYINGGNLEQ-LLDSNEPLS 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 435 VSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL---VNRHYAKISDFGLSKALgADDSYYTARSAGKWPLKWYAPECI 511
Cdd:cd14155  87 WTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrdENGYTAVVGDFGLAEKI-PDYSDGKEKLAVVGSPYWMAPEVL 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 512 NFRKFSSRSDVWSYGVTMWEALSYGQK-----PYKKMKGPEVMAFieqgkrMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd14155 166 RGEPYNEKADVFSYGIILCEIIARIQAdpdylPRTEDFGLDYDAF------QHMVGDCPPDFLQLAFNCCNMDPKSRPSF 239

                ....*..
gi 31455611 587 LTVEQRM 593
Cdd:cd14155 240 HDIVKTL 246
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
321-568 4.45e-24

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 102.44  E-value: 4.45e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 321 DPEELkdkklFLKRDnlliadiELGCGNFGSVRQGVyRMRKKQIdVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVR 400
Cdd:cd06642   1 DPEEL-----FTKLE-------RIGKGSFGEVYKGI-DNRTKEV-VAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITR 66
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 401 LIG-VCQAEALMLVMEMAGGGPLHKFLV-GKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKIS 478
Cdd:cd06642  67 YYGsYLKGTKLWIIMEYLGGGSALDLLKpGPLEE---TYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLA 143
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 479 DFGLSKALgaDDSYYTARSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIeqgkrm 558
Cdd:cd06642 144 DFGVAGQL--TDTQIKRNTFVGTPF-WMAPEVIKQSAYDFKADIWSLGITAIE-LAKGEPPNSDLHPMRVLFLI------ 213
                       250
                ....*....|
gi 31455611 559 ecPPECPPEL 568
Cdd:cd06642 214 --PKNSPPTL 221
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
344-600 4.80e-24

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 102.20  E-value: 4.80e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKqidvaIKVLKQgTEKADTE---EMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:cd14154   1 LGKGFFGQAIKVTHRETGE-----VMVMKE-LIRFDEEaqrNFLKEVKVMRSLDHPNVLKFIGVLyKDKKLNLITEYIPG 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS-------KALGADDSY 492
Cdd:cd14154  75 GTLKDVLKDMARPLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLArliveerLPSGNMSPS 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKWPLK----------WYAPECINFRKFSSRSDVWSYGVTMWEALsyGQKPYKKMKGPEVMAFI--EQGKRMEC 560
Cdd:cd14154 155 ETLRHLKSPDRKkrytvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVLCEII--GRVEADPDYLPRTKDFGlnVDSFREKF 232
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 31455611 561 PPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRACYYSL 600
Cdd:cd14154 233 CAGCPPPFFKLAFLCCDLDPEKRPPFETLEEWLEALYLHL 272
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
343-585 9.06e-24

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 100.95  E-value: 9.06e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKqIDVAIKVLKQ----GTEKADTEEMMREAQIMHQLDNPYIVR-LIGVCQAEALMLVMEMA 417
Cdd:cd08529   7 KLGKGSFGVV----YKVVRK-VDGRVYALKQidisRMSRKMREEAIDEARVLSKLNSPYVIKyYDSFVDKGKLNIVMEYA 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKR-EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYytAR 496
Cdd:cd08529  82 ENGDLHSLIKSQRgRPLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILSDTTNF--AQ 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 497 SAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCW 576
Cdd:cd08529 160 TIVGTPY-YLSPELCEDKPYNEKSDVWALGCVLYE-LCTGKHPFEAQNQGALILKIVRGKYPPISASYSQDLSQLIDSCL 237

                ....*....
gi 31455611 577 IYKWEDRPD 585
Cdd:cd08529 238 TKDYRQRPD 246
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
344-586 1.09e-23

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 100.52  E-value: 1.09e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdVAIKVL-KQGTEKADTEeMMREAQIMHQLDNPYIVRLIGvCQ--AEALMLVMEMAGGG 420
Cdd:cd14120   1 IGHGAFAVVFKGRHRKKPDLP-VAIKCItKKNLSKSQNL-LGKEIKILKELSHENVVALLD-CQetSSSVYLVMEYCNGG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL---------VNRHYAKISDFGLSKALgaDDS 491
Cdd:cd14120  78 DLADYLQAKGT-LSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLshnsgrkpsPNDIRLKIADFGFARFL--QDG 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 492 YYTARSAGKwPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK--RMECPPECPPELY 569
Cdd:cd14120 155 MMAATLCGS-PM-YMAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPFQAQTPQELKAFYEKNAnlRPNIPSGTSPALK 231
                       250
                ....*....|....*..
gi 31455611 570 ALMSDCWIYKWEDRPDF 586
Cdd:cd14120 232 DLLLGLLKRNPKDRIDF 248
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
161-245 1.19e-23

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 94.99  E-value: 1.19e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611    161 MPWYHSSLTREEAERKLYSGAqtDGKFLLRP-RKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYL 239
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG--DGDFLVRDsESSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHY 78

                   ....*.
gi 31455611    240 KLKADG 245
Cdd:smart00252  79 QKNSLG 84
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
343-544 1.45e-23

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270977 [Multi-domain]  Cd Length: 255  Bit Score: 100.10  E-value: 1.45e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMM-REAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd14075   9 ELGSGNFSQVKLGIHQLTKEK--VAIKILDKTKLDQKTQRLLsREISSMEKLHHPNIIRLYEVVETLSkLHLVMEYASGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLV--GKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArsA 498
Cdd:cd14075  87 ELYTKISteGKLSE---SEAKPLFAQIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFSTHAKRGETLNTF--C 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 499 GKWPlkWYAPECinfrkFSSRS------DVWSYGVTMWEALSyGQKPYK-----KMK 544
Cdd:cd14075 162 GSPP--YAAPEL-----FKDEHyigiyvDIWALGVLLYFMVT-GVMPFRaetvaKLK 210
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
344-589 2.19e-23

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 99.98  E-value: 2.19e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKK----QIDVAIKVLkQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGG 419
Cdd:cd14208   7 LGKGSFTKIYRGLRTDEEDdercETEVLLKVM-DPTHGNCQESFLEAASIMSQISHKHLVLLHGVCVGKDSIMVQEFVCH 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREE--IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV------NRHYAKISDFGLSKALgADDS 491
Cdd:cd14208  86 GALDLYLKKQQQKgpVAISWKLQVVKQLAYALNYLEDKQLVHGNVSAKKVLLSregdkgSPPFIKLSDPGVSIKV-LDEE 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 492 YYTARsagkwpLKWYAPECI-NFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECppELYA 570
Cdd:cd14208 165 LLAER------IPWVAPECLsDPQNLALEADKWGFGATLWEIFSGGHMPLSALDPSKKLQFYNDRKQLPAPHWI--ELAS 236
                       250
                ....*....|....*....
gi 31455611 571 LMSDCWIYKWEDRPDFLTV 589
Cdd:cd14208 237 LIQQCMSYNPLLRPSFRAI 255
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
344-573 2.36e-23

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 99.51  E-value: 2.36e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDV--AIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAG 418
Cdd:cd05123   1 LGKGSFGKV----LLVRKKDTGKlyAMKVLRKKEiiKRKEVEHTLNERNILERVNHPFIVKLHYAFQtEEKLYLVLDYVP 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHkFLVGKREEIPVSNV----AELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyYT 494
Cdd:cd05123  77 GGELF-SHLSKEGRFPEERArfyaAEIV----LALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSSDGD-RT 150
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 495 ARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMAFIEQGKrMECPPECPPELYALMS 573
Cdd:cd05123 151 YTFCGT--PEYLAPEVLLGKGYGKAVDWWSLGVLLYEML-TGKPPFYAENRKEIYEKILKSP-LKFPEYVSPEAKSLIS 225
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
321-568 2.66e-23

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 100.15  E-value: 2.66e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 321 DPEELkdkklFLKRDnlliadiELGCGNFGSVRQGV-YRMRKKqidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIV 399
Cdd:cd06641   1 DPEEL-----FTKLE-------KIGKGSFGEVFKGIdNRTQKV---VAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVT 65
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 400 RLIG-VCQAEALMLVMEMAGGGPLHKFL-VGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKI 477
Cdd:cd06641  66 KYYGsYLKDTKLWIIMEYLGGGSALDLLePGPLDE---TQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKL 142
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 478 SDFGLSKALgaDDSYYTARSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIeqgkr 557
Cdd:cd06641 143 ADFGVAGQL--TDTQIKRN*FVGTPF-WMAPEVIKQSAYDSKADIWSLGITAIE-LARGEPPHSELHPMKVLFLI----- 213
                       250
                ....*....|.
gi 31455611 558 mecPPECPPEL 568
Cdd:cd06641 214 ---PKNNPPTL 221
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
358-589 2.94e-23

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 99.98  E-value: 2.94e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 358 RMRKKQIDVAIKVLKQgTEKADTEEMMREAQIMHQLDNPYIVRLIGVC--QAEALMlVMEMAGGGPLHKFLVGKREEIPV 435
Cdd:cd05076  38 RDRGQELRVVLKVLDP-SHHDIALAFFETASLMSQVSHTHLVFVHGVCvrGSENIM-VEEFVEHGPLDVWLRKEKGHVPM 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 436 SNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH-------YAKISDFGLskALGAddsyyTARSAGKWPLKWYAP 508
Cdd:cd05076 116 AWKFVVARQLASALSYLENKNLVHGNVCAKNILLARLGleegtspFIKLSDPGV--GLGV-----LSREERVERIPWIAP 188
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 509 ECI-NFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMEcPPECpPELYALMSDCWIYKWEDRPDFL 587
Cdd:cd05076 189 ECVpGGNSLSTAADKWGFGATLLEICFNGEAPLQSRTPSEKERFYQRQHRLP-EPSC-PELATLISQCLTYEPTQRPSFR 266

                ..
gi 31455611 588 TV 589
Cdd:cd05076 267 TI 268
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
344-595 4.19e-23

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 99.61  E-value: 4.19e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDVAIKVLKQGTEKADTEE---MM-----------------REAQIMHQLDNPYIVRLIG 403
Cdd:cd14000   2 LGDGGFGSV----YRASYKGEPVAVKIFNKHTSSNFANVpadTMlrhlratdamknfrllrQELTVLSHLHHPSIVYLLG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 404 VCqAEALMLVMEMAGGGPLHKFLV-GKREEIPVSNVAE--LLHQVSMGMKYLEEKNFVHRDLAARNVLL----VNRH-YA 475
Cdd:cd14000  78 IG-IHPLMLVLELAPLGSLDHLLQqDSRSFASLGRTLQqrIALQVADGLRYLHSAMIIYRDLKSHNVLVwtlyPNSAiII 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 476 KISDFGLSKalgaddsyYTARSAGKW---PLKWYAPECINFRK-FSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAF 551
Cdd:cd14000 157 KIADYGISR--------QCCRMGAKGsegTPGFRAPEIARGNViYNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEFDI 228
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 31455611 552 IEQGKRMECPPEC--PPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd14000 229 HGGLRPPLKQYECapWPEVEVLMKKCWKENPQQRPTAVTVVSILNS 274
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
344-589 4.28e-23

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 99.11  E-value: 4.28e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQ-GTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQaEALMLVMEMAGGGPL 422
Cdd:cd14025   4 VGSGGFGQVYKVRHKHWKTWL--AIKCPPSlHVDDSERMELLEEAKKMEMAKFRHILPVYGICS-EPVGLVMEYMETGSL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGkrEEIPVSNVAELLHQVSMGMKYLEEKN--FVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGK 500
Cdd:cd14025  81 EKLLAS--EPLPWELRFRIIHETAVGMNFLHCMKppLLHLDLKPANILLDAHYHVKISDFGLAKWNGLSHSHDLSRDGLR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WPLKWYAPECI--NFRKFSSRSDVWSYGVTMWEALSYgQKPYKKMKG-PEVMAFIEQGKRMECPPEC---PPE---LYAL 571
Cdd:cd14025 159 GTIAYLPPERFkeKNRCPDTKHDVYSFAIVIWGILTQ-KKPFAGENNiLHIMVKVVKGHRPSLSPIPrqrPSEcqqMICL 237
                       250
                ....*....|....*...
gi 31455611 572 MSDCWIYKWEDRPDFLTV 589
Cdd:cd14025 238 MKRCWDQDPRKRPTFQDI 255
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
344-591 8.39e-23

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 98.49  E-value: 8.39e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmRKKQIDVAIKVLKQGTEKADTeeMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14221   1 LGKGCFGQAIKVTHR-ETGEVMVMKELIRFDEETQRT--FLKEVKVMRCLEHPNVLKFIGVLYKDKrLNFITEYIKGGTL 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKWP 502
Cdd:cd14221  78 RGIIKSMDSHYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDEKTQPEGLRSLKKP 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 503 LK-----------WYAPECINFRKFSSRSDVWSYGVTMWEALSYGQK-----PYKKMKGPEVMAFIEQgkrmECPPECPP 566
Cdd:cd14221 158 DRkkrytvvgnpyWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNAdpdylPRTMDFGLNVRGFLDR----YCPPNCPP 233
                       250       260
                ....*....|....*....|....*
gi 31455611 567 ELYALMSDCWIYKWEDRPDFLTVEQ 591
Cdd:cd14221 234 SFFPIAVLCCDLDPEKRPSFSKLEH 258
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
321-568 1.06e-22

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 98.20  E-value: 1.06e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 321 DPEELkdkklFLKRDnlliadiELGCGNFGSVRQGVYRmRKKQIdVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVR 400
Cdd:cd06640   1 DPEEL-----FTKLE-------RIGKGSFGEVFKGIDN-RTQQV-VAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTK 66
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 401 LIG-VCQAEALMLVMEMAGGGPLHKFL-VGKREEIpvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKIS 478
Cdd:cd06640  67 YYGsYLKGTKLWIIMEYLGGGSALDLLrAGPFDEF---QIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLA 143
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 479 DFGLSKALgaDDSYYTARSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIeqgkrm 558
Cdd:cd06640 144 DFGVAGQL--TDTQIKRNTFVGTPF-WMAPEVIQQSAYDSKADIWSLGITAIE-LAKGEPPNSDMHPMRVLFLI------ 213
                       250
                ....*....|
gi 31455611 559 ecPPECPPEL 568
Cdd:cd06640 214 --PKNNPPTL 221
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
344-562 1.12e-22

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 97.86  E-value: 1.12e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADTEE----MMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAG 418
Cdd:cd06632   8 LGSGSFGSVYEGFNGDTGDFF--AVKEVSLVDDDKKSREsvkqLEQEIALLSKLRHPNIVQYYGTEREEDnLYIFLEYVP 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFL--VGKREEIPVSNVAEllhQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsyyTAR 496
Cdd:cd06632  86 GGSIHKLLqrYGAFEEPVIRLYTR---QILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVEAFS---FAK 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 497 SAGKWPLkWYAPECINfRKFSS---RSDVWSYGVTMWEaLSYGQKPYKKMKGpeVMAFIEQGKRMECPP 562
Cdd:cd06632 160 SFKGSPY-WMAPEVIM-QKNSGyglAVDIWSLGCTVLE-MATGKPPWSQYEG--VAAIFKIGNSGELPP 223
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
344-556 2.89e-22

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 96.43  E-value: 2.89e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVL-KQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGP 421
Cdd:cd14072   8 IGKGNFAKVK--LARHVLTGREVAIKIIdKTQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEkTLYLVMEYASGGE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLV--GKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArsAG 499
Cdd:cd14072  86 VFDYLVahGRMKE---KEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPGNKLDTF--CG 160
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 500 KWPlkWYAPECINFRKFSS-RSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK 556
Cdd:cd14072 161 SPP--YAAPELFQGKKYDGpEVDVWSLGVILYTLVS-GSLPFDGQNLKELRERVLRGK 215
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
356-586 5.34e-22

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 95.66  E-value: 5.34e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 356 VYRMRKKqIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPLHKFLVgkREEIP 434
Cdd:cd14156   9 VYKVTHG-ATGKVMVVKIYKNDVDQHKIVREISLLQKLSHPNIVRYLGICvKDEKLHPILEYVSGGCLEELLA--REELP 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 435 VS--NVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL---VNRHYAKISDFGLskalgaddsyytARSAGKWPLK----- 504
Cdd:cd14156  86 LSwrEKVELACDISRGMVYLHSKNIYHRDLNSKNCLIrvtPRGREAVVTDFGL------------AREVGEMPANdperk 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 505 --------WYAPECINFRKFSSRSDVWSYGVTMWEALSYGQK-----PYKKMKGPEVMAFIEQgkrmecPPECPPELYAL 571
Cdd:cd14156 154 lslvgsafWMAPEMLRGEPYDRKVDVFSFGIVLCEILARIPAdpevlPRTGDFGLDVQAFKEM------VPGCPEPFLDL 227
                       250
                ....*....|....*
gi 31455611 572 MSDCWIYKWEDRPDF 586
Cdd:cd14156 228 AASCCRMDAFKRPSF 242
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
344-574 7.04e-22

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270822 [Multi-domain]  Cd Length: 277  Bit Score: 96.00  E-value: 7.04e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQL---DNPYIVRLIG-VCQAEALMLVMEMAGG 419
Cdd:cd06917   9 VGRGSYGAVYRGYHVKTGRV--VALKVLNLDTDDDDVSDIQKEVALLSQLklgQPKNIIKYYGsYLKGPSLWIIMDYCEG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyytARSAG 499
Cdd:cd06917  87 GSIRTLM--RAGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSS---KRSTF 161
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 500 KWPLKWYAPECI-NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGKrmecPPECPPELY-ALMSD 574
Cdd:cd06917 162 VGTPYWMAPEVItEGKYYDTKADIWSLGITTYE-MATGNPPYSDVDALRAVMLIPKSK----PPRLEGNGYsPLLKE 233
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
344-567 9.06e-22

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 95.29  E-value: 9.06e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYR-----MRKKQIDV-AIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEM 416
Cdd:cd06628   8 IGSGSFGSVYLGMNAssgelMAVKQVELpSVSAENKDRKKSMLDALQREIALLRELQHENIVQYLGSsSDANHLNIFLEY 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFL--VGKREEIPVSNvaeLLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAdDSYYT 494
Cdd:cd06628  88 VPGGSVATLLnnYGAFEESLVRN---FVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEA-NSLST 163
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 495 ARSAGKWPLK----WYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRMECPPECPPE 567
Cdd:cd06628 164 KNNGARPSLQgsvfWMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFPDCTQMQAIFKIGENASPTIPSNISSE 239
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
344-577 1.58e-21

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 94.50  E-value: 1.58e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKAD---TEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGG 419
Cdd:cd14070  10 LGEGSFAKVREGLHAVTGEK--VAIKVIDKKKAKKDsyvTKNLRREGRIQQMIRHPNITQLLDILETEnSYYLVMELCPG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPL-HKFLVGKREEipVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS---KALGADDSYYTA 495
Cdd:cd14070  88 GNLmHRIYDKKRLE--EREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSncaGILGYSDPFSTQ 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWPlkwyAPECINFRKFSSRSDVWSYGVTMWEALSyGQKP-----------YKKMKGPEV-----------MAFIE 553
Cdd:cd14070 166 CGSPAYA----APELLARKKYGPKVDVWSIGVNMYAMLT-GTLPftvepfslralHQKMVDKEMnplptdlspgaISFLR 240
                       250       260
                ....*....|....*....|....
gi 31455611 554 QGkrMECPPECPPELYALMSDCWI 577
Cdd:cd14070 241 SL--LEPDPLKRPNIKQALANRWL 262
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
344-556 1.65e-21

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 94.21  E-value: 1.65e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQ--IDVAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMAGGG 420
Cdd:cd14103   1 LGRGKFGTV----YRCVEKAtgKELAAKFIKCRKAK-DREDVRNEIEIMNQLRHPRLLQLYDAFETPREMvLVMEYVAGG 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNR--HYAKISDFGLSKALGADDsyytarsa 498
Cdd:cd14103  76 ELFERVVDDDFELTERDCILFMRQICEGVQYMHKQGILHLDLKPENILCVSRtgNQIKIIDFGLARKYDPDK-------- 147
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 499 gkwPLK-------WYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK 556
Cdd:cd14103 148 ---KLKvlfgtpeFVAPEVVNYEPISYATDMWSVGVICYVLLS-GLSPFMGDNDAETLANVTRAK 208
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
344-545 2.27e-21

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 93.87  E-value: 2.27e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVL-KQGTEKADTEE-MMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd14079  10 LGVGSFGKVKLAEHELTGHK--VAVKILnRQKIKSLDMEEkIRREIQILKLFRHPHIIRLYEVIETPTdIFMVMEYVSGG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAGK 500
Cdd:cd14079  88 ELFDYIV-QKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLSNIM--RDGEFLKTSCGS 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 501 wPlKWYAPECINFRKFS-SRSDVWSYGVTMWeALSYGQKP---------YKKMKG 545
Cdd:cd14079 165 -P-NYAAPEVISGKLYAgPEVDVWSCGVILY-ALLCGSLPfddehipnlFKKIKS 216
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
344-573 2.32e-21

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 94.01  E-value: 2.32e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLKQgtEKADTEEMM----REAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAG 418
Cdd:cd14663   8 LGEGTFAKVKFA--RNTKTGESVAIKIIDK--EQVAREGMVeqikREIAIMKLLRHPNIVELHEVMATKTkIFFVMELVT 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS---KALGADDSYYTa 495
Cdd:cd14663  84 GGELFSKIA-KNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSalsEQFRQDGLLHT- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 rSAGKwPlKWYAPECINFRKF-SSRSDVWSYGVTMWEALSyGQKPYKKmkgPEVMAF---IEQGkRMECPPECPPELYAL 571
Cdd:cd14663 162 -TCGT-P-NYVAPEVLARRGYdGAKADIWSCGVILFVLLA-GYLPFDD---ENLMALyrkIMKG-EFEYPRWFSPGAKSL 233

                ..
gi 31455611 572 MS 573
Cdd:cd14663 234 IK 235
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
344-600 2.92e-21

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 94.33  E-value: 2.92e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyrmrKKQIDVAIKVLKQGTEKADTEEMMR-EAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGPL 422
Cdd:cd14149  20 IGSGSFGTVYKG-----KWHGDVAVKILKVVDPTPEQFQAFRnEVAVLRKTRHVNILLFMGYMTKDNLAIVTQWCEGSSL 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlgadDSYYTARSAGKWP 502
Cdd:cd14149  95 YKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATV----KSRWSGSQQVEQP 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 503 ---LKWYAPECINFRK---FSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIeQGKRMECP------PECPPELYA 570
Cdd:cd14149 171 tgsILWMAPEVIRMQDnnpFSFQSDVYSYGIVLYELMT-GELPYSHINNRDQIIFM-VGRGYASPdlsklyKNCPKAMKR 248
                       250       260       270
                ....*....|....*....|....*....|
gi 31455611 571 LMSDCWIYKWEDRPDFLTVEQRMRACYYSL 600
Cdd:cd14149 249 LVADCIKKVKEERPLFPQILSSIELLQHSL 278
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
344-588 3.06e-21

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270892 [Multi-domain]  Cd Length: 279  Bit Score: 93.92  E-value: 3.06e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvYRMrKKQIDVAIKV---LKQGTE--KAD-TEEMMREAQIMHQLDNPYIVRLIGVCQ--AEALMLVME 415
Cdd:cd13990   8 LGKGGFSEVYKA-FDL-VEQRYVACKIhqlNKDWSEekKQNyIKHALREYEIHKSLDHPRIVKLYDVFEidTDSFCTVLE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKFLvgKREE-IPVSNVAELLHQVSMGMKYLEEKN--FVHRDLAARNVLLVNRHYA---KISDFGLSKALgAD 489
Cdd:cd13990  86 YCDGNDLDFYL--KQHKsIPEREARSIIMQVVSALKYLNEIKppIIHYDLKPGNILLHSGNVSgeiKITDFGLSKIM-DD 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 DSYY------TARSAGKWplkWY-APECI----NFRKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMAF---IEQG 555
Cdd:cd13990 163 ESYNsdgmelTSQGAGTY---WYlPPECFvvgkTPPKISSKVDVWSVGVIFYQML-YGRKPFGHNQSQEAILEentILKA 238
                       250       260       270
                ....*....|....*....|....*....|....*
gi 31455611 556 KRMECP--PECPPELYALMSDCWIYKWEDRPDFLT 588
Cdd:cd13990 239 TEVEFPskPVVSSEAKDFIRRCLTYRKEDRPDVLQ 273
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
341-530 3.16e-21

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 93.23  E-value: 3.16e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 341 DIE--LGCGNFGSVRQGVYRMRKKQidVAIKVL-KQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEM 416
Cdd:cd14071   3 DIErtIGKGNFAVVKLARHRITKTE--VAIKIIdKSQLDEENLKKIYREVQIMKMLNHPHIIKLYQVMETKDmLYLVTEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTAr 496
Cdd:cd14071  81 ASNGEIFDYLA-QHGRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKPGELLKTW- 158
                       170       180       190
                ....*....|....*....|....*....|....*
gi 31455611 497 sAGKWPlkWYAPECINFRKFSS-RSDVWSYGVTMW 530
Cdd:cd14071 159 -CGSPP--YAAPEVFEGKEYEGpQLDIWSLGVVLY 190
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
9-93 3.80e-21

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 87.67  E-value: 3.80e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611      9 PFFYGSISRAEAEEHLKlaGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFYS 88
Cdd:smart00252   2 PWYHGFISREEAEKLLK--NEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHYQ 79

                   ....*
gi 31455611     89 RDPDG 93
Cdd:smart00252  80 KNSLG 84
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
343-549 5.29e-21

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 93.43  E-value: 5.29e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKK--QIDVAIKVL--KQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMA 417
Cdd:cd05581   8 PLGEGSYSTV----VLAKEKetGKEYAIKVLdkRHIIKEKKVKYVTIEKEVLSRLAHPGIVKLYYTFQDESkLYFVLEYA 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFL--VGKREEIPVSN-VAELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYT 494
Cdd:cd05581  84 PNGDLLEYIrkYGSLDEKCTRFyTAEIV----LALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLGPDSSPES 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 495 ARSAGKWPLKWY--------------APECINFRKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVM 549
Cdd:cd05581 160 TKGDADSQIAYNqaraasfvgtaeyvSPELLNEKPAGKSSDLWALGCIIYQML-TGKPPFRGSNEYLTF 227
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
161-254 6.97e-21

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 87.83  E-value: 6.97e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 161 MPWYHSSLTREEAERKLYSGAQTDGKFLLRP-RKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYL 239
Cdd:cd09938   1 LPFFYGSITREEAEEYLKLAGMSDGLFLLRQsLRSLGGYVLSVCHGRKFHHYTIERQLNGTYAIAGGKAHCGPAELCEYH 80
                        90
                ....*....|....*
gi 31455611 240 KLKADGLIYCLKEAC 254
Cdd:cd09938  81 STDLDGLVCLLRKPC 95
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
345-542 8.51e-21

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 92.32  E-value: 8.51e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 345 GCGNFGSVRQgVYRMRKKQIdVAIKVLKQG--TEKADTEEMMREAQIMHQLDNPYIVRL-IGVCQAEALMLVMEMAGGGP 421
Cdd:cd05578   9 GKGSFGKVCI-VQKKDTKKM-FAMKYMNKQkcIEKDSVRNVLNELEILQELEHPFLVNLwYSFQDEEDMYMVVDLLLGGD 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYYTARSAGKw 501
Cdd:cd05578  87 L-RYHLQQKVKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKL-TDGTLATSTSGTK- 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 502 plKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYKK 542
Cdd:cd05578 164 --PYMAPEVFMRAGYSFAVDWWSLGVTAYEML-RGKRPYEI 201
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
343-540 8.69e-21

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 92.55  E-value: 8.69e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgvYRMRKKQIDVAIKVLKQGTEKA-----DTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEM 416
Cdd:cd14105  12 ELGSGQFAVVKK--CREKSTGLEYAAKFIKKRRSKAsrrgvSREDIEREVSILRQVLHPNIITLHDVFENKTdVVLILEL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLVGKrEEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNR----HYAKISDFGLSKALGADDSY 492
Cdd:cd14105  90 VAGGELFDFLAEK-ESLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKnvpiPRIKLIDFGLAHKIEDGNEF 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 493 ytaRSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14105 169 ---KNIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPF 211
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
343-543 1.04e-20

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 92.50  E-value: 1.04e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQIDV--AIKVLKQGTEkADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd06611  12 ELGDGAFGKV----YKAQHKETGLfaAAKIIQIESE-EELEDFMVEIDILSECKHPNIVGLYEAYFYENkLWILIEFCDG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSkALGADDSyyTARSAG 499
Cdd:cd06611  87 GALDSIMLELERGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVS-AKNKSTL--QKRDTF 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 500 KWPLKWYAPE---CINFRK--FSSRSDVWSYGVTMWEaLSYGQKPYKKM 543
Cdd:cd06611 164 IGTPYWMAPEvvaCETFKDnpYDYKADIWSLGITLIE-LAQMEPPHHEL 211
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
344-586 1.20e-20

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 92.38  E-value: 1.20e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGPL 422
Cdd:cd14201  14 VGHGAFAVVFKGRHR-KKTDWEVAIKSINKKNLSKSQILLGKEIKILKELQHENIVALYDVQEMpNSVFLVMEYCNGGDL 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGK---REEipvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL--VNRHYA-------KISDFGLSKALgadD 490
Cdd:cd14201  93 ADYLQAKgtlSED----TIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLsyASRKKSsvsgiriKIADFGFARYL---Q 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTARSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMAFIEQGKRME--CPPECPPEL 568
Cdd:cd14201 166 SNMMAATLCGSPM-YMAPEVIMSQHYDAKADLWSIGTVIYQCL-VGKPPFQANSPQDLRMFYEKNKNLQpsIPRETSPYL 243
                       250
                ....*....|....*...
gi 31455611 569 YALMSDCWIYKWEDRPDF 586
Cdd:cd14201 244 ADLLLGLLQRNQKDRMDF 261
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
344-533 1.56e-20

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 91.97  E-value: 1.56e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKK--QIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAGGG 420
Cdd:cd13996  14 LGSGGFGSV----YKVRNKvdGVTYAIKKIRLTEKSSASEKVLREVKALAKLNHPNIVRYYTAwVEEPPLYIQMELCEGG 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLvGKREEIPVSN---VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHY-AKISDFGLSKALGADDSY---- 492
Cdd:cd13996  90 TLRDWI-DRRNSSSKNDrklALELFKQILKGVSYIHSKGIVHRDLKPSNIFLDNDDLqVKIGDFGLATSIGNQKRElnnl 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 493 -------YTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd13996 169 nnnnngnTSNNSVGIGTPLYASPEQLDGENYNEKADIYSLGIILFEML 216
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
340-534 1.68e-20

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 91.32  E-value: 1.68e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 340 ADIELGCGNFGSVRQGVYRmrKKQIDVAIKVLKQGTEKADTEEMMR-EAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMA 417
Cdd:cd14082   7 PDEVLGSGQFGIVYGGKHR--KTGRDVAIKVIDKLRFPTKQESQLRnEVAILQQLSHPGVVNLECMFETpERVFVVMEKL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH---YAKISDFGLSKALGaDDSYyt 494
Cdd:cd14082  85 HGDMLEMILSSEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLASAEpfpQVKLCDFGFARIIG-EKSF-- 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 31455611 495 ARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd14082 162 RRSVVGTP-AYLAPEVLRNKGYNRSLDMWSVGVIIYVSLS 200
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
344-586 1.84e-20

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 91.66  E-value: 1.84e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyrmrKKQIDVAIKVLK-QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGPL 422
Cdd:cd14151  16 IGSGSFGTVYKG-----KWHGDVAVKMLNvTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSL 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGA-DDSYYTARSAGKw 501
Cdd:cd14151  91 YHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRwSGSHQFEQLSGS- 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 pLKWYAPECINFRK---FSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEvmAFIEQGKRMECPPE-------CPPELYAL 571
Cdd:cd14151 170 -ILWMAPEVIRMQDknpYSFQSDVYAFGIVLYELMT-GQLPYSNINNRD--QIIFMVGRGYLSPDlskvrsnCPKAMKRL 245
                       250
                ....*....|....*
gi 31455611 572 MSDCWIYKWEDRPDF 586
Cdd:cd14151 246 MAECLKKKRDERPLF 260
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
344-584 1.89e-20

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 91.00  E-value: 1.89e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVL-KQGTEKADTEEMM-REAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGG 420
Cdd:cd14007   8 LGKGKFGNVY--LAREKKSGFIVALKVIsKSQLQKSGLEHQLrREIEIQSHLRHPNILRLYGYFEdKKRIYLILEYAPNG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKR---EEIpvsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADdsyytARS 497
Cdd:cd14007  86 ELYKELKKQKrfdEKE----AAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSVHAPSN-----RRK 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 --AGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMAFIEQGKrMECPPECPPELYALMSDC 575
Cdd:cd14007 157 tfCGT--LDYLPPEMVEGKEYDYKVDIWSLGVLCYELL-VGKPPFESKSHQETYKRIQNVD-IKFPSSVSPEAKDLISKL 232

                ....*....
gi 31455611 576 WIYKWEDRP 584
Cdd:cd14007 233 LQKDPSKRL 241
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
339-593 3.13e-20

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271067 [Multi-domain]  Cd Length: 263  Bit Score: 90.61  E-value: 3.13e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 339 IADIELGCGNFGSVRQGvYRMRKKQiDVAIKVLKQGTEKADTEE--MMREAQIMHQLDNPYIVRLIGVCQAEA--LMLVM 414
Cdd:cd14165   4 ILGINLGEGSYAKVKSA-YSERLKC-NVAIKIIDKKKAPDDFVEkfLPRELEILARLNHKSIIKTYEIFETSDgkVYIVM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFlVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYT 494
Cdd:cd14165  82 ELGVQGDLLEF-IKLRGALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLRDENGRI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 495 ARSA---GKwpLKWYAPECINFRKFSSR-SDVWSYGVTMWeALSYGQKPYKKMKGPEvMAFIEQGKRMECPPECppelyA 570
Cdd:cd14165 161 VLSKtfcGS--AAYAAPEVLQGIPYDPRiYDIWSLGVILY-IMVCGSMPYDDSNVKK-MLKIQKEHRVRFPRSK-----N 231
                       250       260
                ....*....|....*....|....*
gi 31455611 571 LMSDC--WIYKWEdRPDfltVEQRM 593
Cdd:cd14165 232 LTSECkdLIYRLL-QPD---VSQRL 252
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
344-540 3.21e-20

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 91.01  E-value: 3.21e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQ---IDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMA 417
Cdd:cd14076   9 LGEGEFGKVKLGWPLPKANHrsgVQVAIKLIRRDTqqENCQTSKIMREINILKGLTHPNIVRLLDVLKTKKYIgIVLEFV 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd14076  89 SGGELFDYILARRR-LKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANTFDHFNGDLMSTS 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 498 AGKwPLkWYAPECINFRKF--SSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14076 168 CGS-PC-YAAPELVVSDSMyaGRKADIWSCGVILYAMLA-GYLPF 209
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
361-586 3.33e-20

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 90.77  E-value: 3.33e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 361 KKQIDVAIKVLKQGtEKADTEEMMREAQIMHQLDNPYIVRLIGVC--QAEALMlVMEMAGGGPLHKFLVGKREEIPVSNV 438
Cdd:cd05077  34 EKEIKVILKVLDPS-HRDISLAFFETASMMRQVSHKHIVLLYGVCvrDVENIM-VEEFVEFGPLDLFMHRKSDVLTTPWK 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 439 AELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH-------YAKISDFGLSKALgaddsyyTARSAGKWPLKWYAPECI 511
Cdd:cd05077 112 FKVAKQLASALSYLEDKDLVHGNVCTKNILLAREGidgecgpFIKLSDPGIPITV-------LSRQECVERIPWIAPECV 184
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611 512 -NFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEqGKRMECPPECpPELYALMSDCWIYKWEDRPDF 586
Cdd:cd05077 185 eDSKNLSIAADKWSFGTTLWEICYNGEIPLKDKTLAEKERFYE-GQCMLVTPSC-KELADLMTHCMNYDPNQRPFF 258
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
346-586 3.60e-20

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 90.53  E-value: 3.60e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 346 CGNFGSVRQGVYRMRKKQ-----IDVAIKVLkqGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:cd13992   3 CGSGASSHTGEPKYVKKVgvyggRTVAIKHI--TFSRTEKRTILQELNQLKELVHDNLNKFIGICiNPPNIAVVTEYCTR 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLvgKREEIPV------SNVAELLHqvsmGMKYL-EEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSY 492
Cdd:cd13992  81 GSLQDVL--LNREIKMdwmfksSFIKDIVK----GMNYLhSSSIGYHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTNH 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKWPLKWYAPECINFRKFSSR----SDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECP------P 562
Cdd:cd13992 155 QLDEDAQHKKLLWTAPELLRGSLLEVRgtqkGDVYSFAIILYEILFRSDPFALEREVAIVEKVISGGNKPFRPelavllD 234
                       250       260
                ....*....|....*....|....
gi 31455611 563 ECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd13992 235 EFPPRLVLLVKQCWAENPEKRPSF 258
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
343-585 4.24e-20

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270857 [Multi-domain]  Cd Length: 265  Bit Score: 90.29  E-value: 4.24e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgVYRMRKKQIdVAIKVLKQG--TEKaDTEEMMREAQIMHQLDNPYIVRLIG---VCQAEALMLVMEMA 417
Cdd:cd08217   7 TIGKGSFGTVRK-VRRKSDGKI-LVWKEIDYGkmSEK-EKQQLVSEVNILRELKHPNIVRYYDrivDRANTTLYIVMEYC 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREE---IPVSNVAELLHQVSMGMKYLEEKN-----FVHRDLAARNVLLVNRHYAKISDFGLSKALGaD 489
Cdd:cd08217  84 EGGDLAQLIKKCKKEnqyIPEEFIWKIFTQLLLALYECHNRSvgggkILHRDLKPANIFLDSDNNVKLGDFGLARVLS-H 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 DSYYTARSAGKwPLKWyAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELY 569
Cdd:cd08217 163 DSSFAKTYVGT-PYYM-SPELLNEQSYDEKSDIWSLGCLIYELCA-LHPPFQAANQLELAKKIKEGKFPRIPSRYSSELN 239
                       250
                ....*....|....*.
gi 31455611 570 ALMSDCWIYKWEDRPD 585
Cdd:cd08217 240 EVIKSMLNVDPDKRPS 255
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
344-586 4.44e-20

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 90.46  E-value: 4.44e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGGPL 422
Cdd:cd14202  10 IGHGAFAVVFKGRHK-EKHDLEVAVKCINKKNLAKSQTLLGKEIKILKELKHENIVALYDFQEiANSVYLVMEYCNGGDL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV---------NRHYAKISDFGLSKALgaDDSYY 493
Cdd:cd14202  89 ADYLHTMRT-LSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSysggrksnpNNIRIKIADFGFARYL--QNNMM 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 494 TARSAGKwPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRM--ECPPECPPELYAL 571
Cdd:cd14202 166 AATLCGS-PM-YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPFQASSPQDLRLFYEKNKSLspNIPRETSSHLRQL 242
                       250
                ....*....|....*
gi 31455611 572 MSDCWIYKWEDRPDF 586
Cdd:cd14202 243 LLGLLQRNQKDRMDF 257
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
344-540 6.74e-20

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 89.66  E-value: 6.74e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVL--KQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMAGGG 420
Cdd:cd14162   8 LGHGSYAVVKKAYSTKHKCK--VAIKIVskKKAPEDYLQKFLPREIEVIKGLKHPNLICFYEAIETTSRVyIIMELAENG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFlVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK-ALGADDsyytarsaG 499
Cdd:cd14162  86 DLLDY-IRKNGALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFARgVMKTKD--------G 156
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 KWPLK-------WYA-PECINFRKFSSR-SDVWSYGVTMWeALSYGQKPY 540
Cdd:cd14162 157 KPKLSetycgsyAYAsPEILRGIPYDPFlSDIWSMGVVLY-TMVYGRLPF 205
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
343-562 8.57e-20

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 89.29  E-value: 8.57e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGvyRMRKKQIDVAIKVLKQgTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGP 421
Cdd:cd06613   7 RIGSGTYGDVYKA--RNIATGELAAVKVIKL-EPGDDFEIIQQEISMLKECRHPNIVAYFGSYLRrDKLWIVMEYCGGGS 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKF--LVGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAddSYYTARSAG 499
Cdd:cd06613  84 LQDIyqVTGPLSE---LQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSAQLTA--TIAKRKSFI 158
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611 500 KWPLkWYAPECINFRK---FSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIeqGKRMECPP 562
Cdd:cd06613 159 GTPY-WMAPEVAAVERkggYDGKCDIWALGITAIE-LAELQPPMFDLHPMRALFLI--PKSNFDPP 220
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
343-598 1.05e-19

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 89.54  E-value: 1.05e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGP 421
Cdd:cd05086   4 EIGNGWFGKVLLGEIYTGTSVARVVVKELKASANPKEQDDFLQQGEPYYILQHPNILQCVGQCvEAIPYLLVFEFCDLGD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLH----QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsYYTARS 497
Cdd:cd05086  84 LKTYLANQQEKLRGDSQIMLLQrmacEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGFSRYKED-YIETDD 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 AGKWPLKWYAPECINFRK-------FSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPpecPPEL-- 568
Cdd:cd05086 163 KKYAPLRWTAPELVTSFQdgllaaeQTKYSNIWSLGVTLWELFENAAQPYSDLSDREVLNHVIKERQVKLF---KPHLeq 239
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 31455611 569 ------YALMSDCWIYKwEDRPdflTVEQRMRACYY 598
Cdd:cd05086 240 pysdrwYEVLQFCWLSP-EKRP---TAEEVHRLLTY 271
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
344-534 1.12e-19

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 88.86  E-value: 1.12e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKqiDVAIKVLKQGTEKadTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGPL 422
Cdd:cd14006   1 LGRGRFGVVKRCIEKATGR--EFAAKFIPKRDKK--KEAVLREISILNQLQHPRIIQLHEAYESpTELVLILELCSGGEL 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA--KISDFGLSKALGADDSYYTARSAgk 500
Cdd:cd14006  77 LDRLA-ERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLADRPSPqiKIIDFGLARKLNPGEELKEIFGT-- 153
                       170       180       190
                ....*....|....*....|....*....|....
gi 31455611 501 wpLKWYAPECINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd14006 154 --PEFVAPEIVNGEPVSLATDMWSIGVLTYVLLS 185
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
344-526 1.29e-19

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 89.46  E-value: 1.29e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKadtEEM----MREAQIMHQLDNPYIVRLIGV-CQAEALMLVME- 415
Cdd:cd07829   7 LGEGTYGVV----YKAKDKKTGeiVALKKIRLDNEE---EGIpstaLREISLLKELKHPNIVKLLDViHTENKLYLVFEy 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 --MagggPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYY 493
Cdd:cd07829  80 cdQ----DLKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAFGIPLRTY 155
                       170       180       190
                ....*....|....*....|....*....|....*
gi 31455611 494 TARSAgkwpLKWY-APECI-NFRKFSSRSDVWSYG 526
Cdd:cd07829 156 THEVV----TLWYrAPEILlGSKHYSTAVDIWSVG 186
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
343-575 1.58e-19

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 89.32  E-value: 1.58e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQIDV--AIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd06643  12 ELGDGAFGKV----YKAQNKETGIlaAAKVIDTKSEE-ELEDYMVEIDILASCDHPNIVKLLDAFYYENnLWILIEFCAG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS----KALGADDSYYTA 495
Cdd:cd06643  87 GAVDAVMLELERPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVSakntRTLQRRDSFIGT 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 rsagkwPLkWYAPECI-----NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGK--RMECPPECPPEL 568
Cdd:cd06643 167 ------PY-WMAPEVVmcetsKDRPYDYKADVWSLGVTLIE-MAQIEPPHHELNPMRVLLKIAKSEppTLAQPSRWSPEF 238

                ....*..
gi 31455611 569 YALMSDC 575
Cdd:cd06643 239 KDFLRKC 245
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
343-561 1.59e-19

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 88.54  E-value: 1.59e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVyrMRKKQIDVAIKVLKQGTEKADTEEMMR-EAQIMHQLDNPYIVRLIG-VCQAEALMLVMEMAGGG 420
Cdd:cd14069   8 TLGEGAFGEVFLAV--NRNTEEAVAVKFVDMKRAPGDCPENIKkEVCIQKMLSHKNVVRFYGhRREGEFQYLFLEYASGG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLH---KFLVGkreeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADD-SYYTAR 496
Cdd:cd14069  86 ELFdkiEPDVG----MPEDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLATVFRYKGkERLLNK 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 497 SAGKWPlkWYAPECINFRKF-SSRSDVWSYGVTMWeALSYGQKPYKKMKG--PEVMAFIEQGKRMECP 561
Cdd:cd14069 162 MCGTLP--YVAPELLAKKKYrAEPVDVWSCGIVLF-AMLAGELPWDQPSDscQEYSDWKENKKTYLTP 226
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
344-593 1.60e-19

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 89.10  E-value: 1.60e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDVAIKVLKQgTEKADTEEMMR----EAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAG 418
Cdd:cd14158  23 LGEGGFGVV----FKGYINDKNVAVKKLAA-MVDISTEDLTKqfeqEIQVMAKCQHENLVELLGYsCDGPQLCLVYTYMP 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREEIPVS--NVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD-DSYYTA 495
Cdd:cd14158  98 NGSLLDRLACLNDTPPLSwhMRCKIAQGTANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARASEKFsQTIMTE 177
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKwpLKWYAPECINfRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQ-------------GKRM-ECP 561
Cdd:cd14158 178 RIVGT--TAYMAPEALR-GEITPKSDIFSFGVVLLEIIT-GLPPVDENRDPQLLLDIKEeiedeektiedyvDKKMgDWD 253
                       250       260       270
                ....*....|....*....|....*....|..
gi 31455611 562 PECPPELYALMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd14158 254 STSIEAMYSVASQCLNDKKNRRPDIAKVQQLL 285
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
322-540 1.71e-19

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 88.99  E-value: 1.71e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 322 PEELKDKKLFLKRdnlliadieLGCGNFGSVRQGVYRMRKKQidVAIKVLK-------QGTEKADTEEMMREAQIMHQLD 394
Cdd:cd14084   1 PKELRKKYIMSRT---------LGSGACGEVKLAYDKSTCKK--VAIKIINkrkftigSRREINKPRNIETEIEILKKLS 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 395 NPYIVRLIGVCQAE-ALMLVMEMAGGGPLHKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN-- 471
Cdd:cd14084  70 HPCIIKIEDFFDAEdDYYIVLELMEGGELFDRVVSNKR-LKEAICKLYFYQMLLAVKYLHSNGIIHRDLKPENVLLSSqe 148
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611 472 -RHYAKISDFGLSKALGaDDSYYTARSAGkwPLkWYAPECINF---RKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14084 149 eECLIKITDFGLSKILG-ETSLMKTLCGT--PT-YLAPEVLRSfgtEGYTRAVDCWSLGVILFICLS-GYPPF 216
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
159-251 1.79e-19

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 83.59  E-value: 1.79e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGaqTDGKFLLRPRKEQ-GTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVE 237
Cdd:cd09935   1 EKHSWYHGPISRNAAEYLLSSG--INGSFLVRESESSpGQYSISLRYDGRVYHYRISEDSDGKVYVTQEHRFNTLAELVH 78
                        90
                ....*....|....
gi 31455611 238 YLKLKADGLIYCLK 251
Cdd:cd09935  79 HHSKNADGLITTLR 92
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
332-540 2.53e-19

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 88.65  E-value: 2.53e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 332 LKRDNLLIADiELGCGNFGSVRQGVYRmrKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-- 409
Cdd:cd06620   2 LKNQDLETLK-DLGAGNGGSVSKVLHI--PTGTIMAKKVIHIDAKSSVRKQILRELQILHECHSPYIVSFYGAFLNENnn 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 LMLVMEMAGGGPLHKFLvGKREEIPVSNVAELLHQVSMGMKYL-EEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALG- 487
Cdd:cd06620  79 IIICMEYMDCGSLDKIL-KKKGPFPEEVLGKIAVAVLEGLTYLyNVHRIIHRDIKPSNILVNSKGQIKLCDFGVSGELIn 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 488 --ADDSYYTArsagkwplKWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPY 540
Cdd:cd06620 158 siADTFVGTS--------TYMSPERIQGGKYSVKSDVWSLGLSIIE-LALGEFPF 203
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
343-552 2.63e-19

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271096 [Multi-domain]  Cd Length: 269  Bit Score: 88.15  E-value: 2.63e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgvYRMRKKQIDVAIKVLKQGTEKAD-----TEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEM 416
Cdd:cd14194  12 ELGSGQFAVVKK--CREKSTGLQYAAKFIKKRRTKSSrrgvsREDIEREVSILKEIQHPNVITLHEVYENKTdVILILEL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA----KISDFGLSKALGADDSY 492
Cdd:cd14194  90 VAGGELFDFL-AEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVPkpriKIIDFGLAHKIDFGNEF 168
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 ytaRSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFI 552
Cdd:cd14194 169 ---KNIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETLANV 223
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
344-576 2.70e-19

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 87.86  E-value: 2.70e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQ---GTEKAD-TEEMMREAQIMHQLDNPYIVRLI-GVCQAEALMLVMEMAG 418
Cdd:cd08222   8 LGSGNFGTVY--LVSDLKATADEELKVLKEisvGELQPDeTVDANREAKLLSKLDHPAIVKFHdSFVEKESFCIVTEYCE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFL--VGKREEIPVSN-VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNrHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd08222  86 GGDLDDKIseYKKSGTTIDENqILDWFIQLLLAVQYMHERRILHRDLKAKNIFLKN-NVIKVGDFGISRILMGTSDLATT 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWplkWYAPECINFRKFSSRSDVWSYGVTMWE--ALSYGQKPYKKMKgpeVMAFIEQGKRMECPPECPPELYALMS 573
Cdd:cd08222 165 FTGTPY---YMSPEVLKHEGYNSKSDIWSLGCILYEmcCLKHAFDGQNLLS---VMYKIVEGETPSLPDKYSKELNAIYS 238

                ...
gi 31455611 574 DCW 576
Cdd:cd08222 239 RML 241
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
344-585 2.84e-19

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270859 [Multi-domain]  Cd Length: 256  Bit Score: 87.87  E-value: 2.84e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKqIDVAIKVLKQ----GTEKADTEEMMREAQIMHQLDNPYIVRLI-GVCQAEALMLVMEMAG 418
Cdd:cd08220   8 VGRGAYGTV----YLCRRK-DDNKLVIIKQipveQMTKEERQAALNEVKVLSMLHHPNIIEYYeSFLEDKALMIVMEYAP 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLvNRHY--AKISDFGLSKALGADDSYYTA 495
Cdd:cd08220  83 GGTLFEYIQQRKGSlLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILL-NKKRtvVKIGDFGISKILSSKSKAYTV 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAgkwPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDC 575
Cdd:cd08220 162 VGT---PC-YISPELCEGKPYNQKSDIWALGCVLYE-LASLKRAFEAANLPALVLKIMRGTFAPISDRYSEELRHLILSM 236
                       250
                ....*....|
gi 31455611 576 WIYKWEDRPD 585
Cdd:cd08220 237 LHLDPNKRPT 246
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
344-595 2.89e-19

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 88.08  E-value: 2.89e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADtEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14222   1 LGKGFFGQAIKVTHKATGKVM--VMKELIRCDEETQ-KTFLTEVKVMRSLDHPNVLKFIGVLYKDKrLNLLTEFIEGGTL 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKrEEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL-------GADDSYYTA 495
Cdd:cd14222  78 KDFLRAD-DPFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRLIveekkkpPPDKPTTKK 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWPLK----------WYAPECINFRKFSSRSDVWSYGVTMWEALsyGQK-------PYKKMKGPEVMAFIEQGkrm 558
Cdd:cd14222 157 RTLRKNDRKkrytvvgnpyWMAPEMLNGKSYDEKVDIFSFGIVLCEII--GQVyadpdclPRTLDFGLNVRLFWEKF--- 231
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 31455611 559 eCPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd14222 232 -VPKDCPPAFFPLAAICCRLEPDSRPAFSKLEDSFEA 267
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
344-540 3.17e-19

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 87.61  E-value: 3.17e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGsvrqGVYRMR--KKQIDVAIKVL-KQGTEKAD-TEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAG 418
Cdd:cd14186   9 LGKGSFA----CVYRARslHTGLEVAIKMIdKKAMQKAGmVQRVRNEVEIHCQLKHPSILELYNYFEdSNYVYLVLEMCH 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALG-ADDSYYTARS 497
Cdd:cd14186  85 NGEMSRYLKNRKKPFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLKmPHEKHFTMCG 164
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 498 AGkwplKWYAPECINFRKFSSRSDVWSYGVtMWEALSYGQKPY 540
Cdd:cd14186 165 TP----NYISPEIATRSAHGLESDVWSLGC-MFYTLLVGRPPF 202
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
343-591 3.41e-19

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 88.25  E-value: 3.41e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKADTEEMMREAQI-MHQLDNPYIVRLIGVCQAEA----LMLVME 415
Cdd:cd06617   8 ELGRGAYGVV----DKMRHVPTGtiMAVKRIRATVNSQEQKRLLMDLDIsMRSVDCPYTVTFYGALFREGdvwiCMEVMD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAgggpLHKF---LVGKREEIPVSNVAELLHQVSMGMKYLEEK-NFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDS 491
Cdd:cd06617  84 TS----LDKFykkVYDKGLTIPEDILGKIAVSIVKALEYLHSKlSVIHRDVKPSNVLINRNGQVKLCDFGISGYL--VDS 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 492 YYTARSAGKWPlkWYAPECIN----FRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPevmafIEQGKRM--ECPPECP 565
Cdd:cd06617 158 VAKTIDAGCKP--YMAPERINpelnQKGYDVKSDVWSLGITMIE-LATGRFPYDSWKTP-----FQQLKQVveEPSPQLP 229
                       250       260       270
                ....*....|....*....|....*....|.
gi 31455611 566 -----PELYALMSDCWIYKWEDRPDFLTVEQ 591
Cdd:cd06617 230 aekfsPEFQDFVNKCLKKNYKERPNYPELLQ 260
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
343-574 3.79e-19

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 88.96  E-value: 3.79e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYR-----MRKKQIDVAIKvlkqgteKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEM 416
Cdd:cd06650  12 ELGAGNGGVVFKVSHKpsglvMARKLIHLEIK-------PAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGeISICMEH 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKN-FVHRDLAARNVLLVNRHYAKISDFGLSKAL--GADDSYY 493
Cdd:cd06650  85 MDGGSLDQVL-KKAGRIPEQILGKVSIAVIKGLTYLREKHkIMHRDVKPSNILVNSRGEIKLCDFGVSGQLidSMANSFV 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 494 TARSagkwplkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPykkMKGPEvmafieqGKRMECPPECPPELYALMS 573
Cdd:cd06650 164 GTRS-------YMSPERLQGTHYSVQSDIWSMGLSLVE-MAVGRYP---IPPPD-------AKELELMFGCQVEGDAAET 225

                .
gi 31455611 574 D 574
Cdd:cd06650 226 P 226
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
344-594 4.16e-19

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 87.31  E-value: 4.16e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGV--YRMRKkqidVAIKVLKQ-------GTEkadtEEMMREAQIMHQLDNPYIVRLIGVCQAEA---LM 411
Cdd:cd14119   1 LGEGSYGKVKEVLdtETLCR----RAVKILKKrklrripNGE----ANVKREIQILRRLNHRNVIKLVDVLYNEEkqkLY 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 412 LVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGA-DD 490
Cdd:cd14119  73 MVMEYCVGGLQEMLDSAPDKRLPIWQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAEALDLfAE 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTARSAGKwPlKWYAPECINF-RKFSSRS-DVWSYGVTMWEALSyGQKPYkkmKGPEVMAFIEQ-GK-RMECPPECPP 566
Cdd:cd14119 153 DDTCTTSQGS-P-AFQPPEIANGqDSFSGFKvDIWSAGVTLYNMTT-GKYPF---EGDNIYKLFENiGKgEYTIPDDVDP 226
                       250       260
                ....*....|....*....|....*...
gi 31455611 567 ELYALMSDCWIYKWEDRpdfLTVEQRMR 594
Cdd:cd14119 227 DLQDLLRGMLEKDPEKR---FTIEQIRQ 251
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
337-586 4.60e-19

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 87.40  E-value: 4.60e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 337 LLIADIeLGCGNFGSVRQGVYRMrkkqiDVAIKVLK-----QGTEKADTEEMMREAQIMHqlDNpyIVRLIGVC-QAEAL 410
Cdd:cd14063   2 LEIKEV-IGKGRFGRVHRGRWHG-----DVAIKLLNidylnEEQLEAFKEEVAAYKNTRH--DN--LVLFMGACmDPPHL 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 411 MLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHyAKISDFGLSKALGADd 490
Cdd:cd14063  72 AIVTSLCKGRTLYSLIHERKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLENGR-VVITDFGLFSLSGLL- 149
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 syYTARSAGKW--PLKW---YAPECI-NFR---------KFSSRSDVWSYGvTMWEALSYGQKPYKKMKgPEVMAFiEQG 555
Cdd:cd14063 150 --QPGRREDTLviPNGWlcyLAPEIIrALSpdldfeeslPFTKASDVYAFG-TVWYELLAGRWPFKEQP-AESIIW-QVG 224
                       250       260       270
                ....*....|....*....|....*....|....
gi 31455611 556 KRMECPP---ECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd14063 225 CGKKQSLsqlDIGREVKDILMQCWAYDPEKRPTF 258
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
344-529 5.07e-19

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 87.24  E-value: 5.07e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEE--MMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd14080   8 IGEGSYSKVKLAEYTKSGLKEKVACKIIDKKKAPKDFLEkfLPRELEILRKLRHPNIIQVYSIFERGSkVFIFMEYAEHG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFlVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTAR---- 496
Cdd:cd14080  88 DLLEY-IQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLCPDDDGDVLSKtfcg 166
                       170       180       190
                ....*....|....*....|....*....|....*
gi 31455611 497 SAGkwplkwYA-PECINFRKFSSR-SDVWSYGVTM 529
Cdd:cd14080 167 SAA------YAaPEILQGIPYDPKkYDIWSLGVIL 195
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
344-595 5.15e-19

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 86.93  E-value: 5.15e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRkkqiDVAIKVLKQGTekadTEEMMR-EAQIMHQLDNPYIVRLIGVCQAeALMLVMEMAGGGPL 422
Cdd:cd14068   2 LGDGGFGSVYRAVYRGE----DVAVKIFNKHT----SFRLLRqELVVLSHLHHPSLVALLAAGTA-PRMLVMELAPKGSL 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH-----YAKISDFGLSK---ALGADDSYYT 494
Cdd:cd14068  73 DALLQQDNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTLYpncaiIAKIADYGIAQyccRMGIKTSEGT 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 495 ArsagkwplKWYAPECINFR-KFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIE-QG------KRMECPPEcpP 566
Cdd:cd14068 153 P--------GFRAPEVARGNvIYNQQADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAiQGklpdpvKEYGCAPW--P 222
                       250       260
                ....*....|....*....|....*....
gi 31455611 567 ELYALMSDCWIYKWEDRPDFLTVEQRMRA 595
Cdd:cd14068 223 GVEALIKDCLKENPQCRPTSAQVFDILNS 251
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
344-556 7.63e-19

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 87.12  E-value: 7.63e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqGVYRMRKKQIDVAIKVLKQGTEKADT--EEMMREAQIMHQLDNPYIVR-------LIGVCQAEALMLVM 414
Cdd:cd13989   1 LGSGGFGYV--TLWKHQDTGEYVAIKKCRQELSPSDKnrERWCLEVQIMKKLNHPNVVSardvppeLEKLSPNDLPLLAM 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFL------VGKREeipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV---NRHYAKISDFGLSKA 485
Cdd:cd13989  79 EYCSGGDLRKVLnqpencCGLKE----SEVRTLLSDISSAISYLHENRIIHRDLKPENIVLQqggGRVIYKLIDLGYAKE 154
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31455611 486 LgaDDSYYTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGP-EVMAFIEQGK 556
Cdd:cd13989 155 L--DQGSLCTSFVGT--LQYLAPELFESKKYTCTVDYWSFGTLAFECIT-GYRPFLPNWQPvQWHGKVKQKK 221
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
344-549 7.88e-19

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 87.09  E-value: 7.88e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgvYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA---LMLVMEMAGGG 420
Cdd:cd06621   9 LGEGAGGSVTK--CRLRNTKTIFALKTITTDPNPDVQKQILRELEINKSCASPYIVKYYGAFLDEQdssIGIAMEYCEGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLH------KFLVGKREEIPVSNVAEllhQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD-DSYY 493
Cdd:cd06621  87 SLDsiykkvKKKGGRIGEKVLGKIAE---SVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSGELVNSlAGTF 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 494 TARSagkwplkWY-APECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVM 549
Cdd:cd06621 164 TGTS-------YYmAPERIQGGPYSITSDVWSLGLTLLE-VAQNRFPFPPEGEPPLG 212
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
344-535 8.46e-19

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 86.29  E-value: 8.46e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgVYRMRKKQIdVAIKVLKQGT-EKADTEEMMREAQIMHQLDNPYIVRLI-GVCQAEALMLVMEMAGGGP 421
Cdd:cd08530   8 LGKGSYGSVYK-VKRLSDNQV-YALKEVNLGSlSQKEREDSVNEIRLLASVNHPNIIRYKeAFLDGNRLCIVMEYAPFGD 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLV---GKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADdsyyTARSA 498
Cdd:cd08530  86 LSKLISkrkKKRRLFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKKN----LAKTQ 161
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 31455611 499 GKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSY 535
Cdd:cd08530 162 IGTPL-YAAPEVWKGRPYDYKSDIWSLGCLLYEMATF 197
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
343-540 9.54e-19

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 86.55  E-value: 9.54e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgvYRMRKKQIDVAIKVLKQGTEKADT-----EEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEM 416
Cdd:cd14196  12 ELGSGQFAIVKK--CREKSTGLEYAAKFIKKRQSRASRrgvsrEEIEREVSILRQVLHPNIITLHDVYENRTdVVLILEL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH----YAKISDFGLSKALGADDSY 492
Cdd:cd14196  90 VSGGELFDFL-AQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNipipHIKLIDFGLAHEIEDGVEF 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 493 ytaRSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14196 169 ---KNIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPF 211
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
343-584 9.80e-19

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 87.01  E-value: 9.80e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQIDV--AIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVM-EMAGG 419
Cdd:cd06644  19 ELGDGAFGKV----YKAKNKETGAlaAAKVIETKSEE-ELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMiEFCPG 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS----KALGADDSYYTA 495
Cdd:cd06644  94 GAVDAIMLELDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSaknvKTLQRRDSFIGT 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 rsagkwPLkWYAPE---CINFRK--FSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGK--RMECPPECPPEL 568
Cdd:cd06644 174 ------PY-WMAPEvvmCETMKDtpYDYKADIWSLGITLIE-MAQIEPPHHELNPMRVLLKIAKSEppTLSQPSKWSMEF 245
                       250
                ....*....|....*.
gi 31455611 569 YALMSDCWIYKWEDRP 584
Cdd:cd06644 246 RDFLKTALDKHPETRP 261
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
344-567 1.36e-18

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 85.77  E-value: 1.36e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQgtEKADTEEMM----REAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAG 418
Cdd:cd14081   9 LGKGQTGLVKLAKHCVTGQK--VAIKIVNK--EKLSKESVLmkveREIAIMKLIEHPNVLKLYDVYENkKYLYLVLEYVS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTarSA 498
Cdd:cd14081  85 GGELFDYLVKKGR-LTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMASLQPEGSLLET--SC 161
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31455611 499 GKwpLKWYAPECINFRKFSSR-SDVWSYGVTMWeALSYGQKPYkkmKGPEVMAFIEQGKR--MECPPECPPE 567
Cdd:cd14081 162 GS--PHYACPEVIKGEKYDGRkADIWSCGVILY-ALLVGALPF---DDDNLRQLLEKVKRgvFHIPHFISPD 227
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
342-540 1.50e-18

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 85.77  E-value: 1.50e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IEL-GCGNFGSVrqgvYRMRKK---QIdVAIK-VLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVME 415
Cdd:cd14002   6 LELiGEGSFGKV----YKGRRKytgQV-VALKfIPKRGKSEKELRNLRQEIEILRKLNHPNIIEMLDSFETKKeFVVVTE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGgPLHKFLV--GKREEIPVSNVAELLhqVSmGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaddSYY 493
Cdd:cd14002  81 YAQG-ELFQILEddGTLPEEEVRSIAKQL--VS-ALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAM----SCN 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 494 TA--RSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPY 540
Cdd:cd14002 153 TLvlTSIKGTPL-YMAPELVQEQPYDHTADLWSLGCILYE-LFVGQPPF 199
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
341-540 1.60e-18

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 85.83  E-value: 1.60e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 341 DIE--LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMA 417
Cdd:cd14191   5 DIEerLGSGKFGQVFRLVEKKTKKVW--AGKFFKAYSAK-EKENIRQEISIMNCLHHPKLVQCVDAFEEKAnIVMVLEMV 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKIS--DFGLSKALgaddsyyta 495
Cdd:cd14191  82 SGGELFERIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTKIKliDFGLARRL--------- 152
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWPL-----KWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14191 153 ENAGSLKVlfgtpEFVAPEVINYEPIGYATDMWSIGVICYILVS-GLSPF 201
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
344-591 1.69e-18

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132969 [Multi-domain]  Cd Length: 286  Bit Score: 86.22  E-value: 1.69e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQ--IDVAIKVLKQgTEKADtEEMMREAQIMHQL-DNPYIVRLIG------VCQAEALMLVM 414
Cdd:cd06638  26 IGKGTYGKV----FKVLNKKngSKAAVKILDP-IHDID-EEIEAEYNILKALsDHPNVVKFYGmyykkdVKNGDQLWLVL 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLVG-----KREEIPVsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgAD 489
Cdd:cd06638 100 ELCNGGSVTDLVKGflkrgERMEEPI--IAYILHEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVSAQL-TS 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 DSYYTARSAGKwPLkWYAPECINFRK-----FSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGKrmecPPEC 564
Cdd:cd06638 177 TRLRRNTSVGT-PF-WMAPEVIACEQqldstYDARCDVWSLGITAIE-LGDGDPPLADLHPMRALFKIPRNP----PPTL 249
                       250       260       270
                ....*....|....*....|....*....|...
gi 31455611 565 -PPELYA-----LMSDCWIYKWEDRPDFLTVEQ 591
Cdd:cd06638 250 hQPELWSnefndFIRKCLTKDYEKRPTVSDLLQ 282
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
335-540 2.26e-18

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 85.36  E-value: 2.26e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 335 DNLLIAD-IELGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADTEemmreAQIMHQL-------DNPYIVRLIGVCQ 406
Cdd:cd14198   6 NNFYILTsKELGRGKFAVVRQCISKSTGQEY--AAKFLKKRRRGQDCR-----AEILHEIavlelakSNPRVVNLHEVYE 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 407 -AEALMLVMEMAGGGPLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHY---AKISDFG 481
Cdd:cd14198  79 tTSEIILILEYAAGGEIFNLCVPDLAEmVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPlgdIKIVDFG 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 482 LSKALGaddSYYTARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14198 159 MSRKIG---HACELREIMGTP-EYLAPEILNYDPITTATDMWNIGVIAYMLLT-HESPF 212
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
344-533 2.69e-18

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 85.46  E-value: 2.69e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIK--VLKQGTEKADTEeMMREAQIMHQL-DNPYIVRLIGVCQA-EALMLVMEMAGG 419
Cdd:cd07832   8 IGEGAHGIVFKAKDRETGET--VALKkvALRKLEGGIPNQ-ALREIKALQACqGHPYVVKLRDVFPHgTGFVLVFEYMLS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GpLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSY-YTARSA 498
Cdd:cd07832  85 S-LSEVLRDEERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEDPRlYSHQVA 163
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 31455611 499 GKWplkWYAPECI-NFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd07832 164 TRW---YRAPELLyGSRKYDEGVDLWAVGCIFAELL 196
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
343-540 3.54e-18

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271097 [Multi-domain]  Cd Length: 271  Bit Score: 85.05  E-value: 3.54e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgvYRMRKKQIDVAIKVLKQ-----GTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEM 416
Cdd:cd14195  12 ELGSGQFAIVRK--CREKGTGKEYAAKFIKKrrlssSRRGVSREEIEREVNILREIQHPNIITLHDIFENKTdVVLILEL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA----KISDFGLSKALGADDSY 492
Cdd:cd14195  90 VSGGELFDFL-AEKESLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVPnpriKLIDFGIAHKIEAGNEF 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 493 ytaRSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14195 169 ---KNIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPF 211
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
344-540 4.31e-18

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 84.59  E-value: 4.31e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVyrMRKKQIDVAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGPL 422
Cdd:cd14190  12 LGGGKFGKVHTCT--EKRTGLKLAAKVINKQNSK-DKEMVLLEIQVMNQLNHRNLIQLYEAIETpNEIVLFMEYVEGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNR--HYAKISDFGLSKAlgaddsyYTARSAGK 500
Cdd:cd14190  89 FERIVDEDYHLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCVNRtgHQVKIIDFGLARR-------YNPREKLK 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 501 WPL---KWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14190 162 VNFgtpEFLSPEVVNYDQVSFPTDMWSMGVITYMLLS-GLSPF 203
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
344-594 4.38e-18

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 84.63  E-value: 4.38e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgVYRMRKKQIDVAIKVLK----QGTEKADTEEMMR----------------EAQIMHQLDNPYIVRLIG 403
Cdd:cd14067   1 LGQGGSGTV---IYRARYQGQPVAVKRFHikkcKKRTDGSADTMLKhlraadamknfsefrqEASMLHSLQHPCIVYLIG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 404 VcQAEALMLVMEMAGGGPLHKFLVGKREE---IPVSNVA--ELLHQVSMGMKYLEEKNFVHRDLAARNVLL----VNRHY 474
Cdd:cd14067  78 I-SIHPLCFALELAPLGSLNTVLEENHKGssfMPLGHMLtfKIAYQIAAGLAYLHKKNIIFCDLKSDNILVwsldVQEHI 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 475 -AKISDFGLSKalgadDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIE 553
Cdd:cd14067 157 nIKLSDYGISR-----QSFHEGALGVEGTPGYQAPEIRPRIVYDEKVDMFSYGMVLYELLS-GQRPSLGHHQLQIAKKLS 230
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 31455611 554 QGKRmecPPECPPE------LYALMSDCWIYKWEDRPDFLTVEQRMR 594
Cdd:cd14067 231 KGIR---PVLGQPEevqffrLQALMMECWDTKPEKRPLACSVVEQMK 274
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
344-552 4.44e-18

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 84.18  E-value: 4.44e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKqgTEKADTEEMMREAQIMHQLDNPYIVRLIG-VCQAEALMLVMEMAGGGPL 422
Cdd:cd06614   8 IGEGASGEVYKATDRATGKE--VAIKKMR--LRKQNKELIINEILIMKECKHPNIVDYYDsYLVGDELWVVMEYMDGGSL 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDS---------Yy 493
Cdd:cd06614  84 TDIITQNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKSkrnsvvgtpY- 162
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 494 tarsagkwplkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFI 552
Cdd:cd06614 163 -----------WMAPEVIKRKDYGPKVDIWSLGIMCIE-MAEGEPPYLEEPPLRALFLI 209
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
162-239 4.90e-18

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 79.04  E-value: 4.90e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 162 PWYHSSLTREEAERKLYSgaQTDGKFLLRPR-KEQGTYALSLIYG-KTVYHYLISQDKAGKYCI-PEGTKFDTLWQLVEY 238
Cdd:cd00173   1 PWFHGSISREEAERLLRG--KPDGTFLVRESsSEPGDYVLSVRSGdGKVKHYLIERNEGGYYLLgGSGRTFPSLPELVEH 78

                .
gi 31455611 239 L 239
Cdd:cd00173  79 Y 79
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
343-586 4.98e-18

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 84.90  E-value: 4.98e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQIDV--AIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGG 419
Cdd:cd06622   8 ELGKGNYGSV----YKVLHRPTGVtmAMKEIRLELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEgAVYMCMEYMDA 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREE--IPVSNVAELLHQVSMGMKYL-EEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAddsyytar 496
Cdd:cd06622  84 GSLDKLYAGGVATegIPEDVLRRITYAVVKGLKFLkEEHNIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVA-------- 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 497 SAGKWPL---KWYAPECINFR------KFSSRSDVWSYGVTMWEaLSYGQKPYKkmkgPEV-------MAFIEQGKRMEC 560
Cdd:cd06622 156 SLAKTNIgcqSYMAPERIKSGgpnqnpTYTVQSDVWSLGLSILE-MALGRYPYP----PETyanifaqLSAIVDGDPPTL 230
                       250       260
                ....*....|....*....|....*.
gi 31455611 561 PPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd06622 231 PSGYSDDAQDFVAKCLNKIPNRRPTY 256
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
344-589 4.99e-18

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 84.48  E-value: 4.99e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDVAIKVLKQ--------GTEKADTEEMMRE-----AQIMHQLDNPYIVRLIGV-CQAEA 409
Cdd:cd08528   8 LGSGAFGCV----YKVRKKSNGQTLLALKEinmtnpafGRTEQERDKSVGDiisevNIIKEQLRHPNIVRYYKTfLENDR 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 LMLVMEMAGGGPLHKFLVG---KREEIPVSNVAELLHQVSMGMKYL-EEKNFVHRDLAARNVLLVNRHYAKISDFGLSKA 485
Cdd:cd08528  84 LYIVMELIEGAPLGEHFSSlkeKNEHFTEDRIWNIFVQMVLALRYLhKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAKQ 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 486 LGADDSYYTArSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYgQKPYKKMKGPEVMAFIEQGKRMECPPECP 565
Cdd:cd08528 164 KGPESSKMTS-VVGT--ILYSCPEIVQNEPYGEKADIWALGCILYQMCTL-QPPFYSTNMLTLATKIVEAEYEPLPEGMY 239
                       250       260
                ....*....|....*....|....*
gi 31455611 566 PE-LYALMSDCWIYKWEDRPDFLTV 589
Cdd:cd08528 240 SDdITFVIRSCLTPDPEARPDIVEV 264
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
344-585 6.70e-18

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270943 [Multi-domain]  Cd Length: 309  Bit Score: 84.73  E-value: 6.70e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQG--TEKADT--EEMMREAQIMHQLDNPYIVRLIGV--CQAEALMLVMEMA 417
Cdd:cd14041  14 LGRGGFSEVYKAFDLTEQRYVAVKIHQLNKNwrDEKKENyhKHACREYRIHKELDHPRIVKLYDYfsLDTDSFCTVLEYC 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKN--FVHRDLAARNVLLVNRHYA---KISDFGLSKALGaDDSY 492
Cdd:cd14041  94 EGNDL-DFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKppIIHYDLKPGNILLVNGTACgeiKITDFGLSKIMD-DDSY 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 -------YTARSAGKWplkWY-APECINF----RKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMA---FIEQGKR 557
Cdd:cd14041 172 nsvdgmeLTSQGAGTY---WYlPPECFVVgkepPKISNKVDVWSVGVIFYQCL-YGRKPFGHNQSQQDILqenTILKATE 247
                       250       260       270
                ....*....|....*....|....*....|
gi 31455611 558 MECPPE--CPPELYALMSDCWIYKWEDRPD 585
Cdd:cd14041 248 VQFPPKpvVTPEAKAFIRRCLAYRKEDRID 277
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
343-540 7.96e-18

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 83.94  E-value: 7.96e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRqgvyRMRKKQ--IDVAIKVLKQGTEKADT-EEMMRE-AQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMA 417
Cdd:cd14106  15 PLGRGKFAVVR----KCIHKEtgKEYAAKFLRKRRRGQDCrNEILHEiAVLELCKDCPRVVNLHEVYEtRSELILILELA 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKrEEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHY---AKISDFGLSKALGADDSYYT 494
Cdd:cd14106  91 AGGELQTLLDEE-ECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTSEFPlgdIKLCDFGISRVIGEGEEIRE 169
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 31455611 495 ArsAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14106 170 I--LGT--PDYVAPEILSYEPISLATDMWSIGVLTYVLLT-GHSPF 210
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
163-246 1.03e-17

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 78.23  E-value: 1.03e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQTDGKFLLRP-RKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYLKL 241
Cdd:cd10348   2 WLHGALDRNEAVEILKQKADADGSFLVRYsRRRPGGYVLTLVYENHVYHFEIQNRDDKWFYIDDGPYFESLEHLIEHYTQ 81

                ....*
gi 31455611 242 KADGL 246
Cdd:cd10348  82 FADGL 86
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
343-586 1.15e-17

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 83.96  E-value: 1.15e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQIDVAIKVlKQGTEKADTEEMMREAQ----IMHQLDNPYIVRLIGVCQAEALMLV-MEMA 417
Cdd:cd06618  22 EIGSGTCGQV----YKMRHKKTGHVMAV-KQMRRSGNKEENKRILMdldvVLKSHDCPYIVKCYGYFITDSDVFIcMELM 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 G----------GGPLHKFLVGKreeIPVSNVAELlhqvsmgmKYLEEK-NFVHRDLAARNVLLVNRHYAKISDFGLSKAL 486
Cdd:cd06618  97 StcldkllkriQGPIPEDILGK---MTVSIVKAL--------HYLKEKhGVIHRDVKPSNILLDESGNVKLCDFGISGRL 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 gaDDSYYTARSAGKWPlkWYAPECI---NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGP-EVMAFIEQgkrmECPP 562
Cdd:cd06618 166 --VDSKAKTRSAGCAA--YMAPERIdppDNPKYDIRADVWSLGISLVE-LATGQFPYRNCKTEfEVLTKILN----EEPP 236
                       250       260       270
                ....*....|....*....|....*....|
gi 31455611 563 ECP------PELYALMSDCWIYKWEDRPDF 586
Cdd:cd06618 237 SLPpnegfsPDFCSFVDLCLTKDHRYRPKY 266
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
386-584 1.43e-17

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 83.20  E-value: 1.43e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 386 EAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGPLHKFL--VGKREEIPVSNVAEllhQVSMGMKYLEEKNFVHRDL 462
Cdd:cd06629  58 EIDTLKDLDHPNIVQYLGFEETEdYFSIFLEYVPGGSIGSCLrkYGKFEEDLVRFFTR---QILDGLAYLHSKGILHRDL 134
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 463 AARNVLLVNRHYAKISDFGLSKAlgADDSYYT-ARSAGKWPLKWYAPECI--NFRKFSSRSDVWSYGVTMWEALSyGQKP 539
Cdd:cd06629 135 KADNILVDLEGICKISDFGISKK--SDDIYGNnGATSMQGSVFWMAPEVIhsQGQGYSAKVDIWSLGCVVLEMLA-GRRP 211
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 540 YKKMKGPEVMafIEQGKRMECPP-----ECPPELYALMSDCWIYKWEDRP 584
Cdd:cd06629 212 WSDDEAIAAM--FKLGNKRSAPPvpedvNLSPEALDFLNACFAIDPRDRP 259
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
344-602 1.82e-17

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 82.31  E-value: 1.82e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKqidVAIKVLKQGTEKaDTEEMM---REAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGG 419
Cdd:cd14161  11 LGKGTYGRVKKARDSSGRL---VAIKSIRKDRIK-DEQDLLhirREIEIMSSLNHPHIISVYEVFEnSSKIVIVMEYASR 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFlVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAg 499
Cdd:cd14161  87 GDLYDY-ISERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDKFLQTYCGS- 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 kwPLkWYAPECINFRKFSS-RSDVWSYGVTMWeALSYGQKPYKKMKGPEVMAFIEQGKRMEcppecPPELyalmSD-CWI 577
Cdd:cd14161 165 --PL-YASPEIVNGRPYIGpEVDSWSLGVLLY-ILVHGTMPFDGHDYKILVKQISSGAYRE-----PTKP----SDaCGL 231
                       250       260
                ....*....|....*....|....*
gi 31455611 578 YKWedrpdFLTVEQRMRACYYSLAS 602
Cdd:cd14161 232 IRW-----LLMVNPERRATLEDVAS 251
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
343-594 1.84e-17

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 82.74  E-value: 1.84e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmRKKQIdVAIKVLKQGTEKadTEEMMREAQIMHQL-DNPYIVRLIGV-------CQAEALMLVM 414
Cdd:cd06608  13 VIGEGTYGKVYKARHK-KTGQL-AAIKIMDIIEDE--EEEIKLEINILRKFsNHPNIATFYGAfikkdppGGDDQLWLVM 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGP---LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgadDS 491
Cdd:cd06608  89 EYCGGGSvtdLVKGLRKKGKRLKEEWIAYILRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSAQL---DS 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 492 YYTARSAGKWPLKWYAPECINFRK-----FSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGK--RMECPPEC 564
Cdd:cd06608 166 TLGRRNTFIGTPYWMAPEVIACDQqpdasYDARCDVWSLGITAIE-LADGKPPLCDMHPMRALFKIPRNPppTLKSPEKW 244
                       250       260       270
                ....*....|....*....|....*....|
gi 31455611 565 PPELYALMSDCWIYKWEDRPdflTVEQRMR 594
Cdd:cd06608 245 SKEFNDFISECLIKNYEQRP---FTEELLE 271
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
343-534 1.89e-17

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 82.54  E-value: 1.89e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADteemmREAQIMHQLDNPYIVRLIG-----------------VC 405
Cdd:cd14047  13 LIGSGGFGQVFKAKHRIDGKT--YAIKRVKLNNEKAE-----REVKALAKLDHPNIVRYNGcwdgfdydpetsssnssRS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 406 QAEALMLVMEMAGGGPLHKFlVGKREEIPVSNVA--ELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS 483
Cdd:cd14047  86 KTKCLFIQMEFCEKGTLESW-IEKRNGEKLDKVLalEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFGLV 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 31455611 484 KALgaddSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd14047 165 TSL----KNDGKRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFELLH 211
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
343-540 2.11e-17

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 82.68  E-value: 2.11e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADTE-EMMREAQIMH-QLDNPYIVRLIGVCQ-AEALMLVMEMAGG 419
Cdd:cd14197  16 ELGRGKFAVVRKCVEKDSGKEF--AAKFMRKRRKGQDCRmEIIHEIAVLElAQANPWVINLHEVYEtASEMILVLEYAAG 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHY---AKISDFGLSKALGADDSyytA 495
Cdd:cd14197  94 GEIFNQCVADREEaFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTSESPlgdIKIVDFGLSRILKNSEE---L 170
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 496 RSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14197 171 REIMGTP-EYVAPEILSYEPISTATDMWSIGVLAYVMLT-GISPF 213
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
344-540 2.22e-17

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 83.00  E-value: 2.22e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEM----MREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAG 418
Cdd:cd07841   8 LGEGTYAVVYKARDKETGRI--VAIKKIKLGERKEAKDGInftaLREIKLLQELKHPNIIGLLDVfGHKSNINLVFEFME 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGpLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSA 498
Cdd:cd07841  86 TD-LEKVIKDKSIVLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLARSFGSPNRKMTHQVV 164
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 499 GkwplKWY-APECInF--RKFSSRSDVWSYGVTMWEALSygQKPY 540
Cdd:cd07841 165 T----RWYrAPELL-FgaRHYGVGVDMWSVGCIFAELLL--RVPF 202
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
343-534 2.60e-17

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143341 [Multi-domain]  Cd Length: 284  Bit Score: 82.53  E-value: 2.60e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGp 421
Cdd:cd07836   7 KLGEGTYATVYKG--RNRTTGEIVALKEIHLDAEEGTPSTAIREISLMKELKHENIVRLHDVIHTENkLMLVFEYMDKD- 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFL--VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAG 499
Cdd:cd07836  84 LKKYMdtHGVRGALDPNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAFGIPVNTFSNEVVT 163
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 31455611 500 KWplkWYAPECI-NFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07836 164 LW---YRAPDVLlGSRTYSTSIDIWSVGCIMAEMIT 196
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
344-541 2.86e-17

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 81.93  E-value: 2.86e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVL-KQGTEKADTE-EMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAG 418
Cdd:cd14116  13 LGKGKFGNV----YLAREKQSKfiLALKVLfKAQLEKAGVEhQLRREVEIQSHLRHPNILRLYGYFHdATRVYLILEYAP 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFL--VGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSkaLGADDSyytAR 496
Cdd:cd14116  89 LGTVYRELqkLSKFDE---QRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWS--VHAPSS---RR 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 497 SAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYK 541
Cdd:cd14116 161 TTLCGTLDYLPPEMIEGRMHDEKVDLWSLGVLCYEFL-VGKPPFE 204
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
344-540 2.99e-17

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 83.20  E-value: 2.99e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMH-QLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd05592   3 LGKGSFGKVM--LAELKGTNQYFAIKALKKDVvlEDDDVECTMIERRVLAlASQHPFLTHLFCTFQTEShLFFVMEYLNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPL--HKFLVGKREEIPVS-NVAELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTAR 496
Cdd:cd05592  81 GDLmfHIQQSGRFDEDRARfYGAEII----CGLQFLHSRGIIYRDLKLDNVLLDREGHIKIADFGMCKENIYGEN--KAS 154
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 497 SAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05592 155 TFCGTP-DYIAPEILKGQKYNQSVDWWSFGVLLYEML-IGQSPF 196
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
344-552 3.18e-17

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271094 [Multi-domain]  Cd Length: 261  Bit Score: 81.93  E-value: 3.18e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVyrMRKKQIDVAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGPL 422
Cdd:cd14192  12 LGGGRFGQVHKCT--ELSTGLTLAAKIIKVKGAK-EREEVKNEINIMNQLNHVNLIQLYDAFESKtNLTLIMEYVDGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNR--HYAKISDFGLSKAlgaddsyYTARSAGK 500
Cdd:cd14192  89 FDRITDESYQLTELDAILFTRQICEGVHYLHQHYILHLDLKPENILCVNStgNQIKIIDFGLARR-------YKPREKLK 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 501 WPL---KWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFI 552
Cdd:cd14192 162 VNFgtpEFLAPEVVNYDFVSFPTDMWSVGVITYMLLS-GLSPFLGETDAETMNNI 215
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
342-551 3.54e-17

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 82.07  E-value: 3.54e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLV-MEMAGGG 420
Cdd:cd06624  14 VVLGKGTFGVVYAA--RDLSTQVRIAIKEIPERDSR-EVQPLHEEIALHSRLSHKNIVQYLGSVSEDGFFKIfMEQVPGG 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREeiPVSN----VAELLHQVSMGMKYLEEKNFVHRDLAARNVlLVNRHYA--KISDFGLSKALgADDSYYT 494
Cdd:cd06624  91 SLSALLRSKWG--PLKDnentIGYYTKQILEGLKYLHDNKIVHRDIKGDNV-LVNTYSGvvKISDFGTSKRL-AGINPCT 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 495 ARSAGKwpLKWYAPECIN--FRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAF 551
Cdd:cd06624 167 ETFTGT--LQYMAPEVIDkgQRGYGPPADIWSLGCTIIE-MATGKPPFIELGEPQAAMF 222
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
344-540 3.73e-17

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 82.32  E-value: 3.73e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgvYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVR-------LIGVCQAEALMLVMEM 416
Cdd:cd14038   2 LGTGGFGNVLR--WINQETGEQVAIKQCRQELSPKNRERWCLEIQIMKRLNHPNVVAardvpegLQKLAPNDLPLLAMEY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFL------VGKREEIpvsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV---NRHYAKISDFGLSKALg 487
Cdd:cd14038  80 CQGGDLRKYLnqfencCGLREGA----ILTLLSDISSALRYLHENRIIHRDLKPENIVLQqgeQRLIHKIIDLGYAKEL- 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 31455611 488 aDDSYYTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14038 155 -DQGSLCTSFVGT--LQYLAPELLEQQKYTVTVDYWSFGTLAFECIT-GFRPF 203
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
335-540 3.79e-17

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270766 [Multi-domain]  Cd Length: 341  Bit Score: 83.12  E-value: 3.79e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 335 DNLLIADIE----LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVC--Q 406
Cdd:cd05615   5 DRVRLTDFNflmvLGKGSFGKVM--LAERKGSDELYAIKILKKDVviQDDDVECTMVEKRVLALQDKPPFLTQLHSCfqT 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 407 AEALMLVMEMAGGGPL--HKFLVGK-REEIPVSNVAEllhqVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS 483
Cdd:cd05615  83 VDRLYFVMEYVNGGDLmyHIQQVGKfKEPQAVFYAAE----ISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMC 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 484 KALGADDsyYTARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05615 159 KEHMVEG--VTTRTFCGTP-DYIAPEIIAYQPYGRSVDWWAYGVLLYEMLA-GQPPF 211
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
347-534 4.79e-17

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270731 [Multi-domain]  Cd Length: 272  Bit Score: 81.49  E-value: 4.79e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 347 GNFGSVrqgvYRMRKKQI-DV-AIKVLKqgteKAD------TEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMA 417
Cdd:cd05579   4 GAYGRV----YLAKKKSTgDLyAIKVIK----KRDmirknqVDSVLAERNILSQAQNPFVVKLYYSFQGKKnLYLVMEYL 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFL--VGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKA---LGADDSY 492
Cdd:cd05579  76 PGGDLYSLLenVGALDE---DVARIYIAEIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKVglvRRQIKLS 152
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 31455611 493 YTARSAGKWPLK---------WYAPECINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd05579 153 IQKKSNGAPEKEdrrivgtpdYLAPEILLGQGHGKTVDWWSLGVILYEFLV 203
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
343-539 4.97e-17

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 82.79  E-value: 4.97e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgvYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGP 421
Cdd:cd06649  12 ELGAGNGGVVTK--VQHKPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGeISICMEHMDGGS 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKN-FVHRDLAARNVLLVNRHYAKISDFGLSKAL--GADDSYYTARSa 498
Cdd:cd06649  90 LDQVLKEAKR-IPEEILGKVSIAVLRGLAYLREKHqIMHRDVKPSNILVNSRGEIKLCDFGVSGQLidSMANSFVGTRS- 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 499 gkwplkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKP 539
Cdd:cd06649 168 ------YMSPERLQGTHYSVQSDIWSMGLSLVE-LAIGRYP 201
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
344-526 8.56e-17

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 80.60  E-value: 8.56e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYR----MRKKQIDVAIKVLkqGTEKAdTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAG 418
Cdd:cd14098   8 LGSGTFAEVKKAVEVetgkMRAIKQIVKRKVA--GNDKN-LQLFQREINILKSLEHPGIVRLIDWYEdDQHIYLVMEYVE 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH--YAKISDFGLSKALGADDSYYTAR 496
Cdd:cd14098  85 GGDLMDFIM-AWGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDpvIVKISDFGLAKVIHTGTFLVTFC 163
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 31455611 497 SAgkwpLKWYAPECINFRK------FSSRSDVWSYG 526
Cdd:cd14098 164 GT----MAYLAPEILMSKEqnlqggYSNLVDMWSVG 195
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
345-533 9.71e-17

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 81.01  E-value: 9.71e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 345 GCGNFGSVRQGvyRMRKKQIDVAIK-VLKqgtekaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-------LMLVME- 415
Cdd:cd14137  13 GSGSFGVVYQA--KLLETGEVVAIKkVLQ------DKRYKNRELQIMRRLKHPNIVKLKYFFYSSGekkdevyLNLVMEy 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MagggP--LHKFL---VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNR--HYAKISDFGLSKALGA 488
Cdd:cd14137  85 M----PetLYRVIrhySKNKQTIPIIYVKLYSYQLFRGLAYLHSLGICHRDIKPQN-LLVDPetGVLKLCDFGSAKRLVP 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 489 DD---SYYTARSagkwplkwY-APECI-NFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd14137 160 GEpnvSYICSRY--------YrAPELIfGATDYTTAIDIWSAGCVLAELL 201
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
344-540 1.06e-16

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 81.12  E-value: 1.06e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA------EALMLVMEMA 417
Cdd:cd14039   1 LGTGGFGNV--CLYQNQETGEKIAIKSCRLELSVKNKDRWCHEIQIMKKLNHPNVVKACDVPEEmnflvnDVPLLAMEYC 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKfLVGKREE---IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN---RHYAKISDFGLSKALgaDDS 491
Cdd:cd14039  79 SGGDLRK-LLNKPENccgLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVLQEingKIVHKIIDLGYAKDL--DQG 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 492 YYTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14039 156 SLCTSFVGT--LQYLAPELFENKSYTVTVDYWSFGTMVFECIA-GFRPF 201
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
344-556 1.12e-16

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270734 [Multi-domain]  Cd Length: 317  Bit Score: 81.29  E-value: 1.12e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRK------KQIdVAIKVLKQGTEKA-DTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVME 415
Cdd:cd05582   3 LGQGSFGKV----FLVRKitgpdaGTL-YAMKVLKKATLKVrDRVRTKMERDILADVNHPFIVKLHYAFQTEGkLYLILD 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKFL---VGKREEipvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlGADDSY 492
Cdd:cd05582  78 FLRGGDLFTRLskeVMFTEE----DVKFYLAELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKE-SIDHEK 152
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31455611 493 YTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK 556
Cdd:cd05582 153 KAYSFCGT--VEYMAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPFQGKDRKETMTMILKAK 213
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
343-586 1.24e-16

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270790 [Multi-domain]  Cd Length: 291  Bit Score: 80.87  E-value: 1.24e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQIDV--AIKVLKQGTEKADTEEMMREAQ-IMHQLDNPYIVRLIGVCQAEA----LMLVME 415
Cdd:cd06616  13 EIGRGAFGTV----NKMLHKPSGTimAVKRIRSTVDEKEQKRLLMDLDvVMRSSDCPYIVKFYGALFREGdcwiCMELMD 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAgggpLHKF--LV--GKREEIPVSNVAELLHQVSMGMKYL-EEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDD 490
Cdd:cd06616  89 IS----LDKFykYVyeVLDSVIPEEILGKIAVATVKALNYLkEELKIIHRDVKPSNILLDRNGNIKLCDFGISGQL--VD 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTARSAGKWPlkWYAPECIN----FRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGP-EVMAFIEQGKrmecPPECP 565
Cdd:cd06616 163 SIAKTRDAGCRP--YMAPERIDpsasRDGYDVRSDVWSLGITLYE-VATGKFPYPKWNSVfDQLTQVVKGD----PPILS 235
                       250       260
                ....*....|....*....|....*....
gi 31455611 566 PELYALMSD--------CWIYKWEDRPDF 586
Cdd:cd06616 236 NSEEREFSPsfvnfvnlCLIKDESKRPKY 264
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
344-540 1.36e-16

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270725 [Multi-domain]  Cd Length: 350  Bit Score: 81.56  E-value: 1.36e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgVYRMRKKQIdVAIKVLKQgtekadtEEMMREAQIMH---------QLDNPYIVRLIGVCQ-AEALMLV 413
Cdd:cd05573   9 IGRGAFGEVWL-VRDKDTGQV-YAMKILRK-------SDMLKREQIAHvraerdilaDADSPWIVRLHYAFQdEDHLYLV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 414 MEMAGGGPLHKFLVgKREEIPVSNV----AEL---LHQV-SMGmkyleeknFVHRDLAARNVLLVNRHYAKISDFGLSKA 485
Cdd:cd05573  80 MEYMPGGDLMNLLI-KYDVFPEETArfyiAELvlaLDSLhKLG--------FIHRDIKPDNILLDADGHIKLADFGLCTK 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 486 LG--ADDSYYTARS----------AGKWPLKWY--------------APECINFRKFSSRSDVWSYGVTMWEALsYGQKP 539
Cdd:cd05573 151 MNksGDRESYLNDSvntlfqdnvlARRRPHKQRrvraysavgtpdyiAPEVLRGTGYGPECDWWSLGVILYEML-YGFPP 229

                .
gi 31455611 540 Y 540
Cdd:cd05573 230 F 230
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
344-592 1.52e-16

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 80.00  E-value: 1.52e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgvyrMRKKQIDVAIKVLKQ----GTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAG 418
Cdd:cd08225   8 IGEGSFGKIY-----LAKAKSDSEHCVIKEidltKMPVKEKEASKKEVILLAKMKHPNIVTFFASFQENGrLFIVMEYCD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVGKR----EEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV-NRHYAKISDFGLSKALgaDDSYY 493
Cdd:cd08225  83 GGDLMKRINRQRgvlfSE---DQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSkNGMVAKLGDFGIARQL--NDSME 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 494 TARSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMS 573
Cdd:cd08225 158 LAYTCVGTPY-YLSPEICQNRPYNNKTDIWSLGCVLYE-LCTLKHPFEGNNLHQLVLKICQGYFAPISPNFSRDLRSLIS 235
                       250
                ....*....|....*....
gi 31455611 574 DCWIYKWEDRPDFLTVEQR 592
Cdd:cd08225 236 QLFKVSPRDRPSITSILKR 254
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
343-573 1.78e-16

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 80.56  E-value: 1.78e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYR-----MRKKQIDVAIK--VLKQgtekadteeMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVM 414
Cdd:cd06615   8 ELGAGNGGVVTKVLHRpsgliMARKLIHLEIKpaIRNQ---------IIRELKVLHECNSPYIVGFYGAFYSDGeISICM 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEK-NFVHRDLAARNVLLVNRHYAKISDFGLSKAL--GADDS 491
Cdd:cd06615  79 EHMDGGSLDQVL-KKAGRIPENILGKISIAVLRGLTYLREKhKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLidSMANS 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 492 YYTARSagkwplkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKP--------YKKMKGPEVMAfIEQGKRMECPPE 563
Cdd:cd06615 158 FVGTRS-------YMSPERLQGTHYTVQSDIWSLGLSLVE-MAIGRYPipppdakeLEAMFGRPVSE-GEAKESHRPVSG 228
                       250
                ....*....|
gi 31455611 564 CPPELYALMS 573
Cdd:cd06615 229 HPPDSPRPMA 238
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
343-540 1.83e-16

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 79.73  E-value: 1.83e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGP 421
Cdd:cd14078  10 TIGSGGFAKVKLATHILTGEK--VAIKIMDKKALGDDLPRVKTEIEALKNLSHQHICRLYHVIETDNkIFMVLEYCPGGE 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKrEEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGL---SKAlGADDSYYTarSA 498
Cdd:cd14078  88 LFDYIVAK-DRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLcakPKG-GMDHHLET--CC 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 499 GKwpLKWYAPECINFRKF-SSRSDVWSYGVTMWeALSYGQKPY 540
Cdd:cd14078 164 GS--PAYAAPELIQGKPYiGSEADVWSMGVLLY-ALLCGFLPF 203
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
325-540 2.09e-16

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 80.63  E-value: 2.09e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  325 LKDKKLFLKRD--NLLIADIE----LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNP 396
Cdd:PTZ00263   1 MKAAYMFTKPDtsSWKLSDFEmgetLGTGSFGRVR--IAKHKGTGEYYAIKCLKKREilKMKQVQHVAQEKSILMELSHP 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  397 YIVRLI-GVCQAEALMLVMEMAGGGPLHKFLvGKREEIPvSNVAELLH-QVSMGMKYLEEKNFVHRDLAARNVLLVNRHY 474
Cdd:PTZ00263  79 FIVNMMcSFQDENRVYFLLEFVVGGELFTHL-RKAGRFP-NDVAKFYHaELVLAFEYLHSKDIIYRDLKPENLLLDNKGH 156
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611  475 AKISDFGLSKALgaDDSYYTARSAgkwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:PTZ00263 157 VKVTDFGFAKKV--PDRTFTLCGT---P-EYLAPEVIQSKGHGKAVDWWTMGVLLYEFIA-GYPPF 215
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
334-540 2.47e-16

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 79.30  E-value: 2.47e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 334 RDNLLIADIeLGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LML 412
Cdd:cd14167   2 RDIYDFREV-LGTGAFSEVV--LAEEKRTQKLVAIKCIAKKALEGKETSIENEIAVLHKIKHPNIVALDDIYESGGhLYL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 413 VMEMAGGGPLHKFLVGKREEIPvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVL---LVNRHYAKISDFGLSKALGAD 489
Cdd:cd14167  79 IMQLVSGGELFDRIVEKGFYTE-RDASKLIFQILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSKIEGSG 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 31455611 490 DSYYTA-RSAGkwplkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14167 158 SVMSTAcGTPG-----YVAPEVLAQKPYSKAVDCWSIGVIAYILLC-GYPPF 203
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
343-531 3.04e-16

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270832 [Multi-domain]  Cd Length: 291  Bit Score: 79.53  E-value: 3.04e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKadtEEM----MREAQIMHQLDNPYIVRLIGVCQAEA------- 409
Cdd:cd07840   6 QIGEGTYGQV----YKARNKKTGelVALKKIRMENEK---EGFpitaIREIKLLQKLDHPNVVRLKEIVTSKGsakykgs 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 LMLVME-----MAGggplhkFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK 484
Cdd:cd07840  79 IYMVFEymdhdLTG------LLDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLAR 152
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 31455611 485 algaddsYYTARSAGKWPLK----WY-APECI-NFRKFSSRSDVWSYGVTMWE 531
Cdd:cd07840 153 -------PYTKENNADYTNRvitlWYrPPELLlGATRYGPEVDMWSVGCILAE 198
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
344-540 3.36e-16

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 78.80  E-value: 3.36e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVyrMRKKQIDVAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14193  12 LGGGRFGQVHKCE--EKSSGLKLAAKIIKARSQK-EKEEVKNEIEVMNQLNHANLIQLYDAFESRNdIVLVMEYVDGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNR--HYAKISDFGLSKAlgaddsyYTARSAGK 500
Cdd:cd14193  89 FDRIIDENYNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVSReaNQVKIIDFGLARR-------YKPREKLR 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 501 WPL---KWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14193 162 VNFgtpEFLAPEVVNYEFVSFPTDMWSLGVIAYMLLS-GLSPF 203
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
347-556 3.58e-16

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 78.68  E-value: 3.58e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 347 GNFGSVrqgvYRMRKKQID--VAIKVLKQGT--EKADTEEMMREAQIMH-QLDNPYIVRLIGVCQA-EALMLVMEMAGGG 420
Cdd:cd05611   7 GAFGSV----YLAKKRSTGdyFAIKVLKKSDmiAKNQVTNVKAERAIMMiQGESPYVAKLYYSFQSkDYLYLVMEYLNGG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaddsyYTARSAGK 500
Cdd:cd05611  83 DCAS-LIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNG------LEKRHNKK 155
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 501 W---PlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMAFIEQGK 556
Cdd:cd05611 156 FvgtP-DYLAPETILGVGDDKMSDWWSLGCVIFEFL-FGYPPFHAETPDAVFDNILSRR 212
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
344-547 4.31e-16

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 78.69  E-value: 4.31e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYrmrKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPL 422
Cdd:cd14664   1 IGRGGAGTVYKGVM---PNGTLVAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGYCsNPTTNLLVYEYMPNGSL 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGkREEIPVSNVAELLHQVSM----GMKYLEEK---NFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd14664  78 GELLHS-RPESQPPLDWETRQRIALgsarGLAYLHHDcspLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMS 156
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 31455611 496 RSAGKWplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPE 547
Cdd:cd14664 157 SVAGSY--GYIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRPFDEAFLDD 205
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
344-595 5.32e-16

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 78.50  E-value: 5.32e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVL--KQGTEKA-DTEEMMR-EAQIMHQLDNPYIVRLIGVCQAEA--LMLVMEMA 417
Cdd:cd13994   1 IGKGATSVVRIVTKKNPRSGVLYAVKEYrrRDDESKRkDYVKRLTsEYIISSKLHHPNIVKVLDLCQDLHgkWCLVMEYC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD---DSYYT 494
Cdd:cd13994  81 PGGDLFTLIE-KADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAEVFGMPaekESPMS 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 495 ARSAGKWPLkwYAPECINFRKFSSRS-DVWSYGVTMWeALSYGQKPYK--KMKGPEVMAFIEQGKRMECPPEcPPELYAL 571
Cdd:cd13994 160 AGLCGSEPY--MAPEVFTSGSYDGRAvDVWSCGIVLF-ALFTGRFPWRsaKKSDSAYKAYEKSGDFTNGPYE-PIENLLP 235
                       250       260
                ....*....|....*....|....*
gi 31455611 572 M-SDCWIYKWEDrPDFltvEQRMRA 595
Cdd:cd13994 236 SeCRRLIYRMLH-PDP---EKRITI 256
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
344-584 5.85e-16

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 78.88  E-value: 5.85e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKadTEEMMREAQIMHQLDN-PYIVRLIGV------CQAEALMLVM 414
Cdd:cd06639  30 IGKGTYGKV----YKVTNKKDGslAAVKILDPISDV--DEEIEAEYNILRSLPNhPNVVKFYGMfykadqYVGGQLWLVL 103
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFL-----VGKREEIPVsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgad 489
Cdd:cd06639 104 ELCNGGSVTELVkgllkCGQRLDEAM--ISYILYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQL--- 178
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 DSYYTARSAGKWPLKWYAPECINFRK-----FSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIeqgKRMECPPEC 564
Cdd:cd06639 179 TSARLRRNTSVGTPFWMAPEVIACEQqydysYDARCDVWSLGITAIE-LADGDPPLFDMHPVKALFKI---PRNPPPTLL 254
                       250       260
                ....*....|....*....|....*
gi 31455611 565 PPELYA-----LMSDCWIYKWEDRP 584
Cdd:cd06639 255 NPEKWCrgfshFISQCLIKDFEKRP 279
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
408-584 6.10e-16

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 80.83  E-value: 6.10e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  408 EALMLVMEMAGGGPLHKFLVGK-REEIPVSN--VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK 484
Cdd:PTZ00267 138 DKLLLIMEYGSGGDLNKQIKQRlKEHLPFQEyeVGLLFYQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSK 217
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  485 ALGADDSYYTARSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSYgQKPYKKMKGPEVMAFIEQGKRMECPPEC 564
Cdd:PTZ00267 218 QYSDSVSLDVASSFCGTPY-YLAPELWERKRYSKKADMWSLGVILYELLTL-HRPFKGPSQREIMQQVLYGKYDPFPCPV 295
                        170       180
                 ....*....|....*....|
gi 31455611  565 PPELYALMSDCWIYKWEDRP 584
Cdd:PTZ00267 296 SSGMKALLDPLLSKNPALRP 315
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
344-565 7.54e-16

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 77.86  E-value: 7.54e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRK----KQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMAG 418
Cdd:cd06631   9 LGKGAYGTVYCGLTSTGQliavKQ--VELDTSDKEKAEKEYEKLQEEVDLLKTLKHVNIVGYLGTCLEDNVVsIFMEFVP 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFL--VGKREEIPVSNVAEllhQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA- 495
Cdd:cd06631  87 GGSIASILarFGALEEPVFCRYTK---QILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLCINLSSGSQs 163
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611 496 ---RSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMkgPEVMAFIEQGKRMECPPECP 565
Cdd:cd06631 164 qllKSMRGTPY-WMAPEVINETGHGRKSDIWSIGCTVFEMAT-GKPPWADM--NPMAAIFAIGSGRKPVPRLP 232
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
344-534 7.71e-16

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 77.66  E-value: 7.71e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvYRMRKKQIdVAIKVLKQgtEKADTEEMMREAQIMHQLDN----PYIVRLIGVCQAEA---LMLVMEM 416
Cdd:cd05118   7 IGEGAFGTVWLA-RDKVTGEK-VAIKKIKN--DFRHPKAALREIKLLKHLNDveghPNIVKLLDVFEHRGgnhLCLVFEL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 aGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA-KISDFGLSKALgaDDSYYTA 495
Cdd:cd05118  83 -MGMNLYELIKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQlKLADFGLARSF--TSPPYTP 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 496 RSAgkwPLkWY-APECINFRKFSSRS-DVWSYGVTMWEALS 534
Cdd:cd05118 160 YVA---TR-WYrAPEVLLGAKPYGSSiDIWSLGCILAELLT 196
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
344-540 8.63e-16

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270889 [Multi-domain]  Cd Length: 259  Bit Score: 77.75  E-value: 8.63e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmrKKQIDVAIKVL-KQGTEKADteeMMREAQIMHQL-DNPYIVRLIGVC--QAEALMLVMEMAGG 419
Cdd:cd13987   1 LGEGTYGKVLLAVHK--GSGTKMALKFVpKPSTKLKD---FLREYNISLELsVHPHIIKTYDVAfeTEDYYVFAQEYAPY 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHY--AKISDFGLSKALGAddsyyTARS 497
Cdd:cd13987  76 GDLFS-IIPPQVGLPEERVKRCAAQLASALDFMHSKNLVHRDIKPENVLLFDKDCrrVKLCDFGLTRRVGS-----TVKR 149
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 498 AGKWpLKWYAPECINFRKFSS-----RSDVWSYGVTM---------WEALSYGQKPY 540
Cdd:cd13987 150 VSGT-IPYTAPEVCEAKKNEGfvvdpSIDVWAFGVLLfccltgnfpWEKADSDDQFY 205
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
344-584 9.98e-16

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270795 [Multi-domain]  Cd Length: 260  Bit Score: 77.40  E-value: 9.98e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGTEKADT----EEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAG 418
Cdd:cd06625   8 LGQGAFGQVY--LCYDADTGRELAVKQVEIDPINTEAskevKALECEIQLLKNLQHERIVQYYGCLQDEkSLSIFMEYMP 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFL--VGKREEipvsNVA-ELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd06625  86 GGSVKDEIkaYGALTE----NVTrKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRLQTICSSTGM 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSygQKPykkmkgP----EVMAFI----EQGKRMECPPECPPE 567
Cdd:cd06625 162 KSVTGTPY-WMSPEVINGEGYGRKADIWSVGCTVVEMLT--TKP------PwaefEPMAAIfkiaTQPTNPQLPPHVSED 232
                       250
                ....*....|....*..
gi 31455611 568 LYALMSDCWIYKWEDRP 584
Cdd:cd06625 233 ARDFLSLIFVRNKKQRP 249
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
344-595 1.18e-15

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 77.39  E-value: 1.18e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADT-------EEMMREAQIMHQLD-NPYIVRLIGVCQAEALM-LVM 414
Cdd:cd14093  11 LGRGVSSTVRRCIEKETGQEF--AVKIIDITGEKSSEneaeelrEATRREIEILRQVSgHPNIIELHDVFESPTFIfLVF 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLVgkrEEIPVS--NVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsy 492
Cdd:cd14093  89 ELCRKGELFDYLT---EVVTLSekKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEGE-- 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 yTARSAGKWPlKWYAPECI------NFRKFSSRSDVWSYGVTMWEALSyGQKPY---KKMkgpeVM-AFIEQGKRMECPP 562
Cdd:cd14093 164 -KLRELCGTP-GYLAPEVLkcsmydNAPGYGKEVDMWACGVIMYTLLA-GCPPFwhrKQM----VMlRNIMEGKYEFGSP 236
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 31455611 563 EcppelyalmsdcwiykWEDRPD--------FLTV--EQRMRA 595
Cdd:cd14093 237 E----------------WDDISDtakdliskLLVVdpKKRLTA 263
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
321-554 1.23e-15

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 78.16  E-value: 1.23e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 321 DPEeLKDkkLFLKRD--NLLIADIELGCGNFGSVrqgvYRMRKKQID--VAIKVL----KQGTEKadTEEMMREAQIMHQ 392
Cdd:cd06633   7 DPE-IAD--LFYKDDpeEIFVDLHEIGHGSFGAV----YFATNSHTNevVAIKKMsysgKQTNEK--WQDIIKEVKFLQQ 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 393 LDNPYIVRLIGVCQAE-ALMLVMEMAGGGPLHKFLVGKReeiPVSNV--AELLHQVSMGMKYLEEKNFVHRDLAARNVLL 469
Cdd:cd06633  78 LKHPNTIEYKGCYLKDhTAWLVMEYCLGSASDLLEVHKK---PLQEVeiAAITHGALQGLAYLHSHNMIHRDIKAGNILL 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 470 VNRHYAKISDFGLSKALGADDSYYTArsagkwPLkWYAPECI---NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGP 546
Cdd:cd06633 155 TEPGQVKLADFGSASIASPANSFVGT------PY-WMAPEVIlamDEGQYDGKVDIWSLGITCIE-LAERKPPLFNMNAM 226

                ....*...
gi 31455611 547 EVMAFIEQ 554
Cdd:cd06633 227 SALYHIAQ 234
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
344-539 1.24e-15

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 78.65  E-value: 1.24e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  344 LGCGNFGSVRQGvYRMRKKQIdVAIKVLKQGTEKADTEE-------------MMREAQIMHQLDNPYIVRLIGV-CQAEA 409
Cdd:PTZ00024  17 LGEGTYGKVEKA-YDTLTGKI-VAIKKVKIIEISNDVTKdrqlvgmcgihftTLRELKIMNEIKHENIMGLVDVyVEGDF 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  410 LMLVME-MAGGgpLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGa 488
Cdd:PTZ00024  95 INLVMDiMASD--LKK-VVDRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLARRYG- 170
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31455611  489 DDSYYTARSAGKWPLK-----------WY-APECI-NFRKFSSRSDVWSYGVTMWEALSygQKP 539
Cdd:PTZ00024 171 YPPYSDTLSKDETMQRreemtskvvtlWYrAPELLmGAEKYHFAVDMWSVGCIFAELLT--GKP 232
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
344-584 1.33e-15

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 77.08  E-value: 1.33e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLKQ----GTEKADT-EEMMREAQIMHQLDNPYIVRLIGVCQAEA--LMLVMEM 416
Cdd:cd06630   8 LGTGAFSSCYQA--RDVKTGTLMAVKQVSFcrnsSSEQEEVvEAIREEIRMMARLNHPNIVRMLGATQHKShfNIFVEWM 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGG---GPLHKFlvGKREEIPVSNvaeLLHQVSMGMKYLEEKNFVHRDLAARNvLLVNR--HYAKISDFGL-----SKAL 486
Cdd:cd06630  86 AGGsvaSLLSKY--GAFSENVIIN---YTLQILRGLAYLHDNQIIHRDLKGAN-LLVDStgQRLRIADFGAaarlaSKGT 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 GADDsyYTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRMECPPECP- 565
Cdd:cd06630 160 GAGE--FQGQLLGT--IAFMAPEVLRGEQYGRSCDVWSVGCVIIEMAT-AKPPWNAEKISNHLALIFKIASATTPPPIPe 234
                       250       260
                ....*....|....*....|..
gi 31455611 566 ---PELYALMSDCWIYKWEDRP 584
Cdd:cd06630 235 hlsPGLRDVTLRCLELQPEDRP 256
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
343-540 1.69e-15

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 77.23  E-value: 1.69e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKqgteKADTEEM------MREAQIMHQLDNPYIVRLIGVCQ-AEALMLVME 415
Cdd:cd05580   8 TLGTGSFGRVRLVKHKDSGKY--YALKILK----KAKIIKLkqvehvLNEKRILSEVRHPFIVNLLGSFQdDRNLYMVME 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKFLVgKREEIPvSNVAELL-HQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYT 494
Cdd:cd05580  82 YVPGGELFSLLR-RSGRFP-NDVAKFYaAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAKRV--KDRTYT 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 495 arsagkwpL----KWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05580 158 --------LcgtpEYLAPEIILSKGHGKAVDWWALGILIYEMLA-GYPPF 198
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
344-540 1.77e-15

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 77.83  E-value: 1.77e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgvyrMRKK------QIdVAIKVLKQGT---EKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLV 413
Cdd:cd05584   4 LGKGGYGKVFQ----VRKTtgsdkgKI-FAMKVLKKASivrNQKDTAHTKAERNILEAVKHPFIVDLHYAFQTGGkLYLI 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 414 MEMAGGGPLhkFLVGKREEIPVSNVAEL-LHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSy 492
Cdd:cd05584  79 LEYLSGGEL--FMHLEREGIFMEDTACFyLAEITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHDGT- 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 493 YTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05584 156 VTHTFCGT--IEYMAPEILTRSGHGKAVDWWSLGALMYDMLT-GAPPF 200
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
344-563 1.86e-15

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270767 [Multi-domain]  Cd Length: 323  Bit Score: 77.73  E-value: 1.86e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSV----RQGVYRMrkkqidVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVC--QAEALMLVME 415
Cdd:cd05616   8 LGKGSFGKVmlaeRKGTDEL------YAVKILKKDVviQDDDVECTMVEKRVLALSGKPPFLTQLHSCfqTMDRLYFVME 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPL--HKFLVGK-REEIPVSNVAEllhqVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsy 492
Cdd:cd05616  82 YVNGGDLmyHIQQVGRfKEPHAVFYAAE----IAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDG-- 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKP-------------------YKKMKGPEVMAFIE 553
Cdd:cd05616 156 VTTKTFCGTP-DYIAPEIIAYQPYGKSVDWWAFGVLLYEMLA-GQAPfegededelfqsimehnvaYPKSMSKEAVAICK 233
                       250
                ....*....|....*.
gi 31455611 554 ------QGKRMECPPE 563
Cdd:cd05616 234 glmtkhPGKRLGCGPE 249
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
9-87 2.39e-15

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 71.33  E-value: 2.39e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKlaGMADGLFLLRQCLRSLGGYVLSLVHDV-RFHHFPIERQLNGTYAIAGGKAHCG-PAELCEF 86
Cdd:cd00173   1 PWFHGSISREEAERLLR--GKPDGTFLVRESSSEPGDYVLSVRSGDgKVKHYLIERNEGGYYLLGGSGRTFPsLPELVEH 78

                .
gi 31455611  87 Y 87
Cdd:cd00173  79 Y 79
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
344-556 2.98e-15

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270890 [Multi-domain]  Cd Length: 316  Bit Score: 77.15  E-value: 2.98e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV---CQAEALMLVMEMAGGG 420
Cdd:cd13988   1 LGQGATANVFRG--RHKKTGDLYAVKVFNNLSFMRPLDVQMREFEVLKKLNHKNIVKLFAIeeeLTTRHKVLVMELCPCG 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLvgkrEE------IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA----KISDFGLSKALGADD 490
Cdd:cd13988  79 SLYTVL----EEpsnaygLPESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMRVIGEDGqsvyKLTDFGAARELEDDE 154
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 491 SYYTARSAGKWpLKWYAPECINFRK-----FSSRSDVWSYGVTMWEALSyGQKPYKKMKGP----EVMAFIEQGK 556
Cdd:cd13988 155 QFVSLYGTEEY-LHPDMYERAVLRKdhqkkYGATVDLWSIGVTFYHAAT-GSLPFRPFEGPrrnkEVMYKIITGK 227
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
343-526 3.10e-15

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270844 [Multi-domain]  Cd Length: 284  Bit Score: 76.39  E-value: 3.10e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAG 418
Cdd:cd07860   7 KIGEGTYGVV----YKARNKLTGevVALKKIRLDTETEGVPSTaIREISLLKELNHPNIVKLLDVIHTENkLYLVFEFLH 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGpLHKFL-VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd07860  83 QD-LKKFMdASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEV 161
                       170       180       190
                ....*....|....*....|....*....|
gi 31455611 498 AGKWplkWYAPEC-INFRKFSSRSDVWSYG 526
Cdd:cd07860 162 VTLW---YRAPEIlLGCKYYSTAVDIWSLG 188
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
162-238 3.20e-15

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 71.56  E-value: 3.20e-15
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 162 PWYHSSLTREEAERKLYSgaQTDGKFLLRPRKEQGT-YALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEY 238
Cdd:cd09940   6 LWFVGEMERDTAENRLEN--RPDGTYLVRVRPQGETqYALSIKYNGDVKHMKIEQRSDGLYYLSESRHFKSLVELVNY 81
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
343-531 4.04e-15

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 76.16  E-value: 4.04e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQI--DVAIK-VLKQGTEKADTEEMMREAQIMHQLDN---PYIVRLIGVCQAEA------L 410
Cdd:cd07838   6 EIGEGAYGTV----YKARDLQDgrFVALKkVRVPLSEEGIPLSTIREIALLKQLESfehPNVVRLLDVCHGPRtdrelkL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 411 MLVMEMAGGGpLHKFL--VGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALga 488
Cdd:cd07838  82 TLVFEHVDQD-LATYLdkCPKPG-LPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLARIY-- 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 489 ddSYYTARSAGKWPLkWY-APECINFRKFSSRSDVWSYGVTMWE 531
Cdd:cd07838 158 --SFEMALTSVVVTL-WYrAPEVLLQSSYATPVDMWSVGCIFAE 198
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
336-585 5.24e-15

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 75.39  E-value: 5.24e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 336 NLLIADIELGCGNFGSVrqgVYRMRKKQIDVAIK-VLKQGTEKADteemmREAQIMHQLDN-PYIVRLIGV--------- 404
Cdd:cd13982   1 KLTFSPKVLGYGSEGTI---VFRGTFDGRPVAVKrLLPEFFDFAD-----REVQLLRESDEhPNVIRYFCTekdrqflyi 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 405 ----CQAEALMLVmemagggplHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV--NRHY---A 475
Cdd:cd13982  73 alelCAASLQDLV---------ESPRESKLFLRPGLEPVRLLRQIASGLAHLHSLNIVHRDLKPQNILIStpNAHGnvrA 143
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 476 KISDFGLSKALGADDSYYTARSAGKWPLKWYAPECI--NFRKFSSRS-DVWSYGVTMWEALSYGQKPYKKMKGPEvmAFI 552
Cdd:cd13982 144 MISDFGLCKKLDVGRSSFSRRSGVAGTSGWIAPEMLsgSTKRRQTRAvDIFSLGCVFYYVLSGGSHPFGDKLERE--ANI 221
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 31455611 553 EQGK--RMECPP--ECPPELYALMSDCWIYKWEDRPD 585
Cdd:cd13982 222 LKGKysLDKLLSlgEHGPEAQDLIERMIDFDPEKRPS 258
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
345-593 5.38e-15

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 75.94  E-value: 5.38e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 345 GCGNFGSVrqgvYRMRKKQIDVAIKVLKQGTEKAdteeMMREAQI----MHQLDNpyIVRLI-----GVCQAEALMLVME 415
Cdd:cd13998   4 GKGRFGEV----WKASLKNEPVAVKIFSSRDKQS----WFREKEIyrtpMLKHEN--ILQFIaaderDTALRTELWLVTA 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNF---------VHRDLAARNVLLVNRHYAKISDFGLSKAL 486
Cdd:cd13998  74 FHPNGSL*DYL--SLHTIDWVSLCRLALSVARGLAHLHSEIPgctqgkpaiAHRDLKSKNILVKNDGTCCIADFGLAVRL 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 GADDSYYTARSAGKWPLKWY-APE----CINFRKFSS--RSDVWSYGVTMWEALS-----------YgQKPYKKMKG--P 546
Cdd:cd13998 152 SPSTGEEDNANNGQVGTKRYmAPEvlegAINLRDFESfkRVDIYAMGLVLWEMASrctdlfgiveeY-KPPFYSEVPnhP 230
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611 547 --EVMAFI--EQGKRMECPP---ECPP--ELYALMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd13998 231 sfEDMQEVvvRDKQRPNIPNrwlSHPGlqSLAETIEECWDHDAEARLTAQCIEERL 286
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
344-556 6.43e-15

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 75.18  E-value: 6.43e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKV--------LKQGTEKADTEEM------MREAQIMHQLDNPYIVRLIGVCQAEA 409
Cdd:cd14077   9 IGAGSMGKVKLAKHIRTGEK--CAIKIiprasnagLKKEREKRLEKEIsrdirtIREAALSSLLNHPHICRLRDFLRTPN 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 -LMLVMEMAGGGPLHKFLV--GKREEIPVSNVAEllhQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL 486
Cdd:cd14077  87 hYYMLFEYVDGGQLLDYIIshGKLKEKQARKFAR---QIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNLY 163
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 31455611 487 GADDSYYTARSAgkwpLKWYAPECINFRKFSS-RSDVWSYGVTMWeALSYGQKPYKKMKGPEVMAFIEQGK 556
Cdd:cd14077 164 DPRRLLRTFCGS----LYFAAPELLQAQPYTGpEVDVWSFGVVLY-VLVCGKVPFDDENMPALHAKIKKGK 229
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
344-531 6.51e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 75.87  E-value: 6.51e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQAEALM---------LV 413
Cdd:cd07865  20 IGQGTFGEVFKA--RHRKTGQIVALKKVLMENEKEGFPITaLREIKILQLLKHENVVNLIEICRTKATPynrykgsiyLV 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 414 ME-----MAGggplhkFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL-- 486
Cdd:cd07865  98 FEfcehdLAG------LLSNKNVKFTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLARAFsl 171
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 487 --GADDSYYTARSAGKWplkWYAPE-CINFRKFSSRSDVWSYGVTMWE 531
Cdd:cd07865 172 akNSQPNRYTNRVVTLW---YRPPElLLGERDYGPPIDMWGAGCIMAE 216
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
344-540 7.38e-15

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270739 [Multi-domain]  Cd Length: 320  Bit Score: 75.89  E-value: 7.38e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSV----RQGVYRMrkkqidVAIKVLKQGT--EKADTEEMMREAQIMHQLDNP-YIVRLIGVCQA-EALMLVME 415
Cdd:cd05587   4 LGKGSFGKVmlaeRKGTDEL------YAIKILKKDViiQDDDVECTMVEKRVLALSGKPpFLTQLHSCFQTmDRLYFVME 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPL--HKFLVGK-REEIPVSNVAEllhqVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSy 492
Cdd:cd05587  78 YVNGGDLmyHIQQVGKfKEPVAVFYAAE----IAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKEGIFGGK- 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 493 yTARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05587 153 -TTRTFCGTP-DYIAPEIIAYQPYGKSVDWWAYGVLLYEMLA-GQPPF 197
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
344-540 8.59e-15

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 74.89  E-value: 8.59e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmrKKQIDVAIKVL---KQGTEKADTEEmmREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMAGG 419
Cdd:cd14097   9 LGQGSFGVVIEATHK--ETQTKWAIKKInreKAGSSAVKLLE--REVDILKHVNHAHIIHLEEVFETPKRMyLVMELCED 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN-------RHYAKISDFGLSKALGADDSY 492
Cdd:cd14097  85 GELKELLLRKGF-FSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKSsiidnndKLNIKVTDFGLSVQKYGLGED 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 493 YTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14097 164 MLQETCGT--PIYMAPEVISAHGYSQQCDIWSIGVIMYMLLC-GEPPF 208
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
344-585 9.14e-15

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270862 [Multi-domain]  Cd Length: 257  Bit Score: 74.40  E-value: 9.14e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALML--VMEMAGGGP 421
Cdd:cd08223   8 IGKGSYGEVWLVRHKRDRKQY-VIKKLNLKNASKRERKAAEQEAKLLSKLKHPNIVSYKESFEGEDGFLyiVMGFCEGGD 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 L-HKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGK 500
Cdd:cd08223  87 LyTRLKEQKGVLLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLESSSDMATTLIGTP 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WplkWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEqGKRMECPPECPPELYALMSDCWIYKW 580
Cdd:cd08223 167 Y---YMSPELFSNKPYNHKSDVWALGCCVYEMATLKHAFNAKDMNSLVYKILE-GKLPPMPKQYSPELGELIKAMLHQDP 242

                ....*
gi 31455611 581 EDRPD 585
Cdd:cd08223 243 EKRPS 247
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
344-530 9.22e-15

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 74.67  E-value: 9.22e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQgtEKADTEEMM--REAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGG 420
Cdd:cd14095   8 IGDGNFAVVKECRDKATDKEY--ALKIIDK--AKCKGKEHMieNEVAILRRVKHPNIVQLIEEYDtDTELYLVMELVKGG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PL--HKFLVGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNRH-----YAKISDFGLskALGADDSYY 493
Cdd:cd14095  84 DLfdAITSSTKFTE---RDASRMVTDLAQALKYLHSLSIVHRDIKPEN-LLVVEHedgskSLKLADFGL--ATEVKEPLF 157
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 31455611 494 TArsAGKwPlKWYAPECINFRKFSSRSDVWSYGVTMW 530
Cdd:cd14095 158 TV--CGT-P-TYVAPEILAETGYGLKVDIWAAGVITY 190
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
344-573 9.76e-15

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 75.43  E-value: 9.76e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGG 420
Cdd:cd05595   3 LGKGTFGKVI--LVREKATGRYYAMKILRKEViiAKDEVAHTVTESRVLQNTRHPFLTALKYAFQThDRLCFVMEYANGG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLhkFLVGKREEIPVSNVAELL-HQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTARSAG 499
Cdd:cd05595  81 EL--FFHLSRERVFTEDRARFYgAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGITDGA--TMKTFC 156
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31455611 500 KWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQgKRMECPPECPPELYALMS 573
Cdd:cd05595 157 GTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHERLFELILM-EEIRFPRTLSPEAKSLLA 227
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
344-545 1.13e-14

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 74.53  E-value: 1.13e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGPL 422
Cdd:cd06619   9 LGHGNGGTVYKAYHLLTRRIL--AVKVIPLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVEnRISICTEFMDGGSL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFlvgkrEEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL-GADDSYYTARSAgkw 501
Cdd:cd06619  87 DVY-----RKIPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLvNSIAKTYVGTNA--- 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 502 plkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKG 545
Cdd:cd06619 159 ---YMAPERISGEQYGIHSDVWSLGISFME-LALGRFPYPQIQK 198
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
344-561 1.29e-14

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 75.35  E-value: 1.29e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMH-QLDNPYIVRLIGVCQA-EALMLVMEMAGG 419
Cdd:cd05619  13 LGKGSFGKVF--LAELKGTNQFFAIKALKKDVvlMDDDVECTMVEKRVLSlAWEHPFLTHLFCTFQTkENLFFVMEYLNG 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPL-------HKFlvgkreEIPVSN--VAELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADD 490
Cdd:cd05619  91 GDLmfhiqscHKF------DLPRATfyAAEII----CGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENMLGD 160
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 31455611 491 SyYTARSAGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMafieQGKRMECP 561
Cdd:cd05619 161 A-KTSTFCGT-P-DYIAPEILLGQKYNTSVDWWSFGVLLYEML-IGQSPFHGQDEEELF----QSIRMDNP 223
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
344-586 1.48e-14

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 74.23  E-value: 1.48e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyrmrKKQIDVAIKVLK-----QGTEKADTEEMMREAQIMHQldnpYIVRLIGVC-QAEALMLVMEMA 417
Cdd:cd14152   8 IGQGRWGKVHRG-----RWHGEVAIRLLEidgnnQDHLKLFKKEVMNYRQTRHE----NVVLFMGACmHPPHLAIITSFC 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAkISDFGL---SKALGADDSYYT 494
Cdd:cd14152  79 KGRTLYSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDFGLfgiSGVVQEGRRENE 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 495 ARSAGKWpLKWYAPECInfRK-----------FSSRSDVWSYGvTMWEALSYGQKPYKKMKGPEVMAFIEQG---KRMEC 560
Cdd:cd14152 158 LKLPHDW-LCYLAPEIV--REmtpgkdedclpFSKAADVYAFG-TIWYELQARDWPLKNQPAEALIWQIGSGegmKQVLT 233
                       250       260
                ....*....|....*....|....*.
gi 31455611 561 PPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd14152 234 TISLGKEVTEILSACWAFDLEERPSF 259
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
344-585 1.57e-14

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270942 [Multi-domain]  Cd Length: 299  Bit Score: 74.71  E-value: 1.57e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQG--TEKADT--EEMMREAQIMHQLDNPYIVRLIGV--CQAEALMLVMEMA 417
Cdd:cd14040  14 LGRGGFSEVYKAFDLYEQRYAAVKIHQLNKSwrDEKKENyhKHACREYRIHKELDHPRIVKLYDYfsLDTDTFCTVLEYC 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKN--FVHRDLAARNVLLVNRHYA---KISDFGLSKALGaDDSY 492
Cdd:cd14040  94 EGNDL-DFYLKQHKLMSEKEARSIVMQIVNALRYLNEIKppIIHYDLKPGNILLVDGTACgeiKITDFGLSKIMD-DDSY 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 ------YTARSAGKWplkWY-APECINF----RKFSSRSDVWSYGVTMWEALsYGQKPYKKMKGPEVMA---FIEQGKRM 558
Cdd:cd14040 172 gvdgmdLTSQGAGTY---WYlPPECFVVgkepPKISNKVDVWSVGVIFFQCL-YGRKPFGHNQSQQDILqenTILKATEV 247
                       250       260
                ....*....|....*....|....*....
gi 31455611 559 ECP--PECPPELYALMSDCWIYKWEDRPD 585
Cdd:cd14040 248 QFPvkPVVSNEAKAFIRRCLAYRKEDRFD 276
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
344-527 1.71e-14

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 73.95  E-value: 1.71e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14083  11 LGTGAFSEVVLAEDKATGKL--VAIKCIDKKALKGKEDSLENEIAVLRKIKHPNIVQLLDIYESKShLYLVMELVTGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLV--GKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLlvnrHYAK-------ISDFGLSKalgADDSYY 493
Cdd:cd14083  89 FDRIVekGSYTE---KDASHLIRQVLEAVDYLHSLGIVHRDLKPENLL----YYSPdedskimISDFGLSK---MEDSGV 158
                       170       180       190
                ....*....|....*....|....*....|....
gi 31455611 494 TARSAGKwPlKWYAPECINFRKFSSRSDVWSYGV 527
Cdd:cd14083 159 MSTACGT-P-GYVAPEVLAQKPYGKAVDCWSIGV 190
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
344-541 1.88e-14

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270722 [Multi-domain]  Cd Length: 318  Bit Score: 74.56  E-value: 1.88e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmRKKQIdVAIKVLKQG--TEKADTEEMMREAQIMHQLDN-PYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd05570   3 LGKGSFGKVMLAERK-KTDEL-YAIKVLKKEviIEDDDVECTMTEKRVLALANRhPFLTGLHACFQTEDrLYFVMEYVNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPL-------HKFlvgkREEIPVSNVAEllhqVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKaLGADDSY 492
Cdd:cd05570  81 GDLmfhiqraRRF----TEERARFYAAE----ICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCK-EGIWGGN 151
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 493 YTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYK 541
Cdd:cd05570 152 TTSTFCGT--PDYIAPEILREQDYGFSVDWWALGVLLYEMLA-GQSPFE 197
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
408-584 1.90e-14

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 73.62  E-value: 1.90e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 408 EALMLVMEMAGGGPLH-KFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL 486
Cdd:cd08221  72 ESLFIEMEYCNGGNLHdKIAQQKNQLFPEEVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISKVL 151
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 gaDDSYYTARSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSYgQKPYKKMKGPEVMAFIEQGKRMECPPECPP 566
Cdd:cd08221 152 --DSESSMAESIVGTPY-YMSPELVQGVKYNFKSDIWAVGCVLYELLTL-KRTFDATNPLRLAVKIVQGEYEDIDEQYSE 227
                       170
                ....*....|....*...
gi 31455611 567 ELYALMSDCWIYKWEDRP 584
Cdd:cd08221 228 EIIQLVHDCLHQDPEDRP 245
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
367-574 1.91e-14

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 74.27  E-value: 1.91e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 367 AIKVLKQGT--EKADTEEMMR-EAQIM-HQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPLHKFLVgKREEIPVSNVAEL 441
Cdd:cd05613  32 AMKVLKKATivQKAKTAEHTRtERQVLeHIRQSPFLVTLHYAFQTDTkLHLILDYINGGELFTHLS-QRERFTENEVQIY 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 442 LHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKwpLKWYAPECINF--RKFSSR 519
Cdd:cd05613 111 IGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFLLDENERAYSFCGT--IEYMAPEIVRGgdSGHDKA 188
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611 520 SDVWSYGVTMWEALSyGQKPYkKMKGpEVMAFIEQGKR-MECPPECPPELYALMSD 574
Cdd:cd05613 189 VDWWSLGVLMYELLT-GASPF-TVDG-EKNSQAEISRRiLKSEPPYPQEMSALAKD 241
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
343-556 2.46e-14

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 73.82  E-value: 2.46e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIdvAIKVLKQgtEKADTEEmmrEAQIMHQLDN-PYIVRLIGVCQ-AEALMLVMEMAGGG 420
Cdd:cd14091   7 EIGKGSYSVCKRCIHKATGKEY--AVKIIDK--SKRDPSE---EIEILLRYGQhPNIITLRDVYDdGNSVYLVTELLRGG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PL------HKFLvGKREeipvsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLlvnrhYA---------KISDFGLSKA 485
Cdd:cd14091  80 ELldrilrQKFF-SERE------ASAVMKTLTKTVEYLHSQGVVHRDLKPSNIL-----YAdesgdpeslRICDFGFAKQ 147
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 486 LGADDSY-----YTArsagkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKkmKGPE-----VMAFIEQG 555
Cdd:cd14091 148 LRAENGLlmtpcYTA--------NFVAPEVLKKQGYDAACDIWSLGVLLYTMLA-GYTPFA--SGPNdtpevILARIGSG 216

                .
gi 31455611 556 K 556
Cdd:cd14091 217 K 217
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
343-531 2.87e-14

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 73.72  E-value: 2.87e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmRKKQIdVAIKVLKQGTEKadTEEMM--REAQIMHQL-DNPYIVRLIGVC-QAEALMLVME-MA 417
Cdd:cd07830   6 QLGDGTFGSVYLARNK-ETGEL-VAIKKMKKKFYS--WEECMnlREVKSLRKLnEHPNIVKLKEVFrENDELYFVFEyME 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGgpLHKfLVGKREEIPVSN--VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd07830  82 GN--LYQ-LMKDRKGKPFSEsvIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRSRPPYTDY 158
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 31455611 496 RSAgkwplKWY-APEcINFR--KFSSRSDVWSYGVTMWE 531
Cdd:cd07830 159 VST-----RWYrAPE-ILLRstSYSSPVDIWALGCIMAE 191
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
344-592 4.05e-14

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173759 [Multi-domain]  Cd Length: 255  Bit Score: 72.70  E-value: 4.05e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGsvRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd08219   8 VGEGSFG--RALLVQHVNSDQKYAMKEIRLPKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGhLYIVMEYCDGGDL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEI-PVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKW 501
Cdd:cd08219  86 MQKIKLQRGKLfPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTSPGAYACTYVGTPY 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 plkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 581
Cdd:cd08219 166 ---YVPPEIWENMPYNNKSDIWSLGCILYE-LCTLKHPFQANSWKNLILKVCQGSYKPLPSHYSYELRSLIKQMFKRNPR 241
                       250
                ....*....|.
gi 31455611 582 DRPDFLTVEQR 592
Cdd:cd08219 242 SRPSATTILSR 252
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
344-540 4.29e-14

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 72.58  E-value: 4.29e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGTEKAD--TEEMMREAQIMHQLDNPYIVRL---IGVCQAEaLMLVMEMAG 418
Cdd:cd14164   8 IGEGSFSKVK--LATSQKYCCKVAIKIVDRRRASPDfvQKFLPRELSILRRVNHPNIVQMfecIEVANGR-LYIVMEAAA 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKflVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL-VNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd14164  85 TDLLQK--IQEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLsADDRKIKIADFGFARFVEDYPELSTTFC 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 498 AGKwplKWYAPECINFRKFSSRS-DVWSYGVTMWeALSYGQKPY 540
Cdd:cd14164 163 GSR---AYTPPEVILGTPYDPKKyDVWSLGVVLY-VMVTGTMPF 202
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
344-587 4.31e-14

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 72.73  E-value: 4.31e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMrkkqiDVAIKVL-----KQGTEKADTEEMMREAQIMHQldnpYIVRLIGVCQAEA-LMLVMEMA 417
Cdd:cd14153   8 IGKGRFGQVYHGRWHG-----EVAIRLIdierdNEEQLKAFKREVMAYRQTRHE----NVVLFMGACMSPPhLAIITSLC 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAkISDFGL---SKALGADDSYYT 494
Cdd:cd14153  79 KGRTLYSVVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGLftiSGVLQAGRREDK 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 495 ARSAGKWpLKWYAPECI---------NFRKFSSRSDVWSYGvTMWEALSYGQKPYKKMKGPEVMAFIEQG-KRMECPPEC 564
Cdd:cd14153 158 LRIQSGW-LCHLAPEIIrqlspeteeDKLPFSKHSDVFAFG-TIWYELHAREWPFKTQPAEAIIWQVGSGmKPNLSQIGM 235
                       250       260
                ....*....|....*....|...
gi 31455611 565 PPELYALMSDCWIYKWEDRPDFL 587
Cdd:cd14153 236 GKEISDILLFCWAYEQEERPTFS 258
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
268-575 5.13e-14

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 73.70  E-value: 5.13e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  268 PTLPAHPSTLTHPQRRID-TLnsdgytPEPARITSPDKPRPMPMDTSVYESPYSD---PEELKDKKLF--LKRDNlliad 341
Cdd:PLN00034  12 LPSTARHTTKSRPRRRPDlTL------PLPQRDPSLAVPLPLPPPSSSSSSSSSSsasGSAPSAAKSLseLERVN----- 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  342 iELGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGG 420
Cdd:PLN00034  81 -RIGSGAGGTVYKVIHRPTGRLY--ALKVIYGNHEDTVRRQICREIEILRDVNHPNVVKCHDMFdHNGEIQVLLEFMDGG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  421 PLHKFLVGKREEIpvsnvAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYYTARSAGK 500
Cdd:PLN00034 158 SLEGTHIADEQFL-----ADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRIL-AQTMDPCNSSVGT 231
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  501 wpLKWYAPECINFRKFSSR-----SDVWSYGVTMWEaLSYGQKPY---KKMKGPEVMAFIEQGKRMECPPECPPELYALM 572
Cdd:PLN00034 232 --IAYMSPERINTDLNHGAydgyaGDIWSLGVSILE-FYLGRFPFgvgRQGDWASLMCAICMSQPPEAPATASREFRHFI 308

                 ...
gi 31455611  573 SDC 575
Cdd:PLN00034 309 SCC 311
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
158-254 5.56e-14

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 68.22  E-value: 5.56e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 158 HERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQ-GTYALSLIYGKTVYHYLI-SQDKAGKYC--IPEG-TKFDTL 232
Cdd:cd09944   2 HRSQPWFHGGISRDEAARLIRQQGLVDGVFLVRESQSNpGAFVLSLKHGQKIKHYQIiPIEDEGQWYftLDDGvTKFYDL 81
                        90       100
                ....*....|....*....|..
gi 31455611 233 WQLVEYLKLKADGLIYCLKEAC 254
Cdd:cd09944  82 LQLVEFYQLNAGSLPTRLKHYC 103
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
344-540 6.56e-14

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270735 [Multi-domain]  Cd Length: 268  Bit Score: 72.04  E-value: 6.56e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRK------KQIdVAIKVLKQGT--EKADT-EEMMREAQIMHQL-DNPYIVRLIGVCQAEA-LML 412
Cdd:cd05583   2 LGTGAYGKV----FLVRKvgghdaGKL-YAMKVLKKATivQKAKTaEHTMTERQVLEAVrQSPFLVTLHYAFQTDAkLHL 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 413 VMEMAGGGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSY 492
Cdd:cd05583  77 ILDYVNGGELFTHLY-QREHFTESEVRIYIGEIVLALEHLHKLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFLPGEND 155
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 493 YTARSAGKwpLKWYAPECIN--FRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05583 156 RAYSFCGT--IEYMAPEVVRggSDGHDKAVDWWSLGVLTYELLT-GASPF 202
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
344-544 6.91e-14

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173720 [Multi-domain]  Cd Length: 285  Bit Score: 72.33  E-value: 6.91e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAiKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGP 421
Cdd:cd05631   8 LGKGGFGEVCACQVRATGKMYACK-KLEKKRIKKRKGEAMaLNEKRILEKVNSRFVVSLAYAYETkDALCLVLTIMNGGD 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LhKFLV------GKREEIPVSNVAELlhqvSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsyyTA 495
Cdd:cd05631  87 L-KFHIynmgnpGFDEQRAIFYAAEL----CCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAVQIPEGE---TV 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RS-AGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMK 544
Cdd:cd05631 159 RGrVGT--VGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQ-GQSPFRKRK 205
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
344-540 7.67e-14

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 72.67  E-value: 7.67e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTE--KADTEEMMREAQIMH-QLDNPYIVRLIGVCQA-EALMLVMEMAGG 419
Cdd:cd05620   3 LGKGSFGKVLLA--ELKGKGEYFAVKALKKDVVliDDDVECTMVEKRVLAlAWENPFLTHLYCTFQTkEHLFFVMEFLNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTARSAG 499
Cdd:cd05620  81 GDL-MFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENVFGDN--RASTFC 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 500 KWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05620 158 GTP-DYIAPEILQGLKYTFSVDWWSFGVLLYEML-IGQSPF 196
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
344-544 9.12e-14

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 72.24  E-value: 9.12e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrQGVYRMRKKQIDVAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGP 421
Cdd:cd05607  10 LGKGGFGEV-CAVQVKNTGQMYACKKLDKKRLKKKSGEKMaLLEKEILEKVNSPFIVSLAYAFETKThLCLVMSLMNGGD 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 L--HKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLskALGADDSYYTARSAG 499
Cdd:cd05607  89 LkyHIYNVGERG-IEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGL--AVEVKEGKPITQRAG 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 500 KwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMK 544
Cdd:cd05607 166 T--NGYMAPEILKEESYSYPVDWFAMGCSIYEMVA-GRTPFRDHK 207
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
344-540 9.38e-14

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270769 [Multi-domain]  Cd Length: 364  Bit Score: 73.14  E-value: 9.38e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQG--TEKADTEEMMREAQIMHQLDN-PYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd05618  28 IGRGSYAKVL--LVRLKKTERIYAMKVVKKElvNDDEDIDWVQTEKHVFEQASNhPFLVGLHSCFQTESrLFFVIEYVNG 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK-ALGADDSyyTARSA 498
Cdd:cd05618 106 GDL-MFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKeGLRPGDT--TSTFC 182
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 31455611 499 GKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05618 183 GT--PNYIAPEILRGEDYGFSVDWWALGVLMFEMMA-GRSPF 221
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
343-591 1.00e-13

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 71.60  E-value: 1.00e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVA-IKVLKQGTEKAdTEEMMREAQIMHQLDNPYIVR-LIGVCQAEALMLVMEMAGGG 420
Cdd:cd08228   9 KIGRGQFSEVYRATCLLDRKPVALKkVQIFEMMDAKA-RQDCVKEIDLLKQLNHPNVIKyLDSFIEDNELNIVLELADAG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLH---KFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTARS 497
Cdd:cd08228  88 DLSqmiKYFKKQKRLIPERTVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTT--AAHS 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 498 AGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPY--KKMKGPEVMAFIEQgkrMECPPeCPPELYA----- 570
Cdd:cd08228 166 LVGTPY-YMSPERIHENGYNFKSDIWSLGCLLYE-MAALQSPFygDKMNLFSLCQKIEQ---CDYPP-LPTEHYSeklre 239
                       250       260
                ....*....|....*....|.
gi 31455611 571 LMSDCWIYKWEDRPDFLTVEQ 591
Cdd:cd08228 240 LVSMCIYPDPDQRPDIGYVHQ 260
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
344-533 1.03e-13

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 71.83  E-value: 1.03e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA------------ 409
Cdd:cd14048  14 LGRGGFGVV----FEAKNKVDDcnYAVKRIRLPNNELAREKVLREVRALAKLDHPGIVRYFNAWLERPpegwqekmdevy 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 LMLVMEMAGGGPLHKFLVGKR--EEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALG 487
Cdd:cd14048  90 LYIQMQLCRKENLKDWMNRRCtmESRELFVCLNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVTAMD 169
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 488 ADDSYYT--------ARSAGKWPLKWY-APECINFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd14048 170 QGEPEQTvltpmpayAKHTGQVGTRLYmSPEQIHGNQYSEKVDIFALGLILFELI 224
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
344-540 1.26e-13

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 71.41  E-value: 1.26e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKqgTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGGPL 422
Cdd:cd14087   9 IGRGSFSRVVRVEHRVTRQPY--AIKMIE--TKCRGREVCESELNVLRRVRHTNIIQLIEVFEtKERVYMVMELATGGEL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLV--GKREEIPVSNVaelLHQVSMGMKYLEEKNFVHRDLAARNVLLVN-RHYAK--ISDFGLSKALGADDSYYTARS 497
Cdd:cd14087  85 FDRIIakGSFTERDATRV---LQMVLDGVKYLHGLGITHRDLKPENLLYYHpGPDSKimITDFGLASTRKKGPNCLMKTT 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 498 AGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14087 162 CGT-P-EYIAPEILLRKPYTQSVDMWAVGVIAYILLS-GTMPF 201
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
344-555 1.32e-13

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 71.18  E-value: 1.32e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVyrMRKKQIDVAIKVLKQ--GTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE--ALMLVMEMAGG 419
Cdd:cd14163   8 IGEGTYSKVKEAF--SKKHQRKVAIKIIDKsgGPEEFIQRFLPRELQIVERLDHKNIIHVYEMLESAdgKIYLVMELAED 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFlVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHyAKISDFGLSKALGADDSYYTARSAG 499
Cdd:cd14163  86 GDVFDC-VLHGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALLQGFT-LKLTDFGFAKQLPKGGRELSQTFCG 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 500 KwpLKWYAPECINFRKFSSRS-DVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQG 555
Cdd:cd14163 164 S--TAYAAPEVLQGVPHDSRKgDIWSMGVVLYVMLC-AQLPFDDTDIPKMLCQQQKG 217
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
158-238 1.32e-13

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 66.91  E-value: 1.32e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 158 HERMPWYHSSLTREEAERKLYSgAQTDGKFLLRPR-KEQGTYALSLIYGKTVYHYLISQDkAGKYCIpeGTK-FDTLWQL 235
Cdd:cd09932   1 HESKEWFHANLTREQAEEMLMR-VPRDGAFLVRPSeTDPNSFAISFRAEGKIKHCRIKQE-GRLFVI--GTSqFESLVEL 76

                ...
gi 31455611 236 VEY 238
Cdd:cd09932  77 VSY 79
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
439-586 1.33e-13

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 71.28  E-value: 1.33e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 439 AELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKwpLKWYAPECIN----FR 514
Cdd:cd14043 100 SSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQNLPLPEPAPEE--LLWTAPELLRdprlER 177
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 515 KFSSRSDVWSYGVTMWEALSYGQkPYKKMKGP--EVmafIEqgKRMECPPEC---------PPELYALMSDCWIYKWEDR 583
Cdd:cd14043 178 RGTFPGDVFSFAIIMQEVIVRGA-PYCMLGLSpeEI---IE--KVRSPPPLCrpsvsmdqaPLECIQLMKQCWSEAPERR 251

                ...
gi 31455611 584 PDF 586
Cdd:cd14043 252 PTF 254
STKc_MRCK_beta cd05624
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control ...
328-540 1.46e-13

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.


Pssm-ID: 270774 [Multi-domain]  Cd Length: 409  Bit Score: 72.73  E-value: 1.46e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 328 KKLFLKRDNLLIADIeLGCGNFGSVrqGVYRMRKKQIDVAIKVLK--QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVC 405
Cdd:cd05624  65 KEMQLHRDDFEIIKV-IGRGAFGEV--AVVKMKNTERIYAMKILNkwEMLKRAETACFREERNVLVNGDCQWITTLHYAF 141
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 406 QAEA-LMLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK 484
Cdd:cd05624 142 QDENyLYLVMDYYVGGDLLTLLSKFEDKLPEDMARFYIGEMVLAIHSIHQLHYVHRDIKPDNVLLDMNGHIRLADFGSCL 221
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 31455611 485 ALGADDSYYTARSAGKwPlKWYAPECIN-----FRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05624 222 KMNDDGTVQSSVAVGT-P-DYISPEILQamedgMGKYGPECDWWSLGVCMYEML-YGETPF 279
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
161-253 1.63e-13

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 66.54  E-value: 1.63e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 161 MPWYHSSLTREEAERKLYSGAqtDGKFLLR-----PrkeqGTYALSLIYGKTVYHYLISQDKaGKYCIPEGTKFDTLWQL 235
Cdd:cd09937   3 MPWFHGKISREEAERLLQPPE--DGLFLVRestnyP----GDYTLCVSFEGKVEHYRVIYRN-GKLTIDEEEYFENLIQL 75
                        90
                ....*....|....*...
gi 31455611 236 VEYLKLKADGLIYCLKEA 253
Cdd:cd09937  76 VEHYTKDADGLCTRLVKP 93
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
346-575 1.64e-13

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 70.85  E-value: 1.64e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 346 CGNFGSVRQGVYRMRKKQIDVAIKVLKQGTE--KADTEEMMREAQIMHQLDNPYIVRLIGVC-------QAEALMLVMEM 416
Cdd:cd14012   6 SGTFYLVYEVVLDNSKKPGKFLTSQEYFKTSngKKQIQLLEKELESLKKLRHPNLVSYLAFSierrgrsDGWKVYLLTEY 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFL--VGKreeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH---YAKISDFGLSKALgaDDS 491
Cdd:cd14012  86 APGGSLSELLdsVGS---VPLDTARRWTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDAgtgIVKLTDYSLGKTL--LDM 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 492 YYTARSAGKWPLKWYAPECINF-RKFSSRSDVWSYGVtMWEALSYGQKPYKKMKGP-EVMAfieqgkrmecPPECPPELY 569
Cdd:cd14012 161 CSRGSLDEFKQTYWLPPELAQGsKSPTRKTDVWDLGL-LFLQMLFGLDVLEKYTSPnPVLV----------SLDLSASLQ 229

                ....*.
gi 31455611 570 ALMSDC 575
Cdd:cd14012 230 DFLSKC 235
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
159-246 1.72e-13

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 66.37  E-value: 1.72e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGAQTDGKFLLR-PRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVE 237
Cdd:cd10370   1 EAEPWYFGKIKRIEAEKKLLLPENEHGAFLIRdSESRHNDYSLSVRDGDTVKHYRIRQLDEGGFFIARRTTFRTLQELVE 80

                ....*....
gi 31455611 238 YLKLKADGL 246
Cdd:cd10370  81 HYSKDSDGL 89
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
344-541 1.79e-13

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 71.86  E-value: 1.79e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDN-PYIVRLIGVCQA-EALMLVMEMAGG 419
Cdd:cd05590   3 LGKGSFGKVM--LARLKESGRLYAVKVLKKDVilQDDDVECTMTEKRILSLARNhPFLTQLYCCFQTpDRLFFVMEFVNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlGADDSYYTARSAG 499
Cdd:cd05590  81 GDL-MFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKE-GIFNGKTTSTFCG 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 31455611 500 KwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYK 541
Cdd:cd05590 159 T-P-DYIAPEILQEMLYGPSVDWWAMGVLLYEMLC-GHAPFE 197
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
343-539 2.01e-13

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 71.15  E-value: 2.01e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKVLK-QGTEKADTEEMMREAQIMHQL---DNPYIVRLIGVC------QAEAL 410
Cdd:cd07863   7 EIGVGAYGTV----YKARDPHSGhfVALKSVRvQTNEDGLPLSTVREVALLKRLeafDHPNIVRLMDVCatsrtdRETKV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 411 MLVMEMAGGGpLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgad 489
Cdd:cd07863  83 TLVFEHVDQD-LRTYLDKVPPPgLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLARIY--- 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 dSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAlsYGQKP 539
Cdd:cd07863 159 -SCQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEM--FRRKP 205
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
344-540 2.22e-13

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 70.28  E-value: 2.22e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGsvrqGVYR---MRKKQIdVAIKVL-KQGTEKADTEE-MMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMA 417
Cdd:cd14099   9 LGKGGFA----KCYEvtdMSTGKV-YAGKVVpKSSLTKPKQREkLKSEIKIHRSLKHPNIVKFHDCFEdEENVYILLELC 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADD------- 490
Cdd:cd14099  84 SNGSLME-LLKRRKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLEYDGerkktlc 162
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 31455611 491 ---SYytarsagkwplkwYAPECINFRK-FSSRSDVWSYGVTMWeALSYGQKPY 540
Cdd:cd14099 163 gtpNY-------------IAPEVLEKKKgHSFEVDIWSLGVILY-TLLVGKPPF 202
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
343-540 2.32e-13

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 70.31  E-value: 2.32e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQI--DVAIKVLKQGTEkADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMAGG 419
Cdd:cd14114   9 ELGTGAFGVV----HRCTERATgnNFAAKFIMTPHE-SDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMvLILEFLSG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA--KISDFGLSKALGADDSYYTARS 497
Cdd:cd14114  84 GELFERIAAEHYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTTKRSNevKLIDFGLATHLDPKESVKVTTG 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 498 AGKWPlkwyAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14114 164 TAEFA----APEIVEREPVGFYTDMWAVGVLSYVLLS-GLSPF 201
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
325-556 2.33e-13

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 71.23  E-value: 2.33e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 325 LKD---KKLFLKRD-NLLIADI-ELGCGNFGSVRQGvYRMRKKQIdVAIKVL----KQGTEKadTEEMMREAQIMHQLDN 395
Cdd:cd06635   9 LKDpdiAELFFKEDpEKLFSDLrEIGHGSFGAVYFA-RDVRTSEV-VAIKKMsysgKQSNEK--WQDIIKEVKFLQRIKH 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 396 PYIVRLIGVCQAE-ALMLVMEMAGGGPLHKFLVGKR--EEIpvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNR 472
Cdd:cd06635  85 PNSIEYKGCYLREhTAWLVMEYCLGSASDLLEVHKKplQEI---EIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEP 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 473 HYAKISDFGLSKALGADDSYYTARSagkwplkWYAPECI---NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVM 549
Cdd:cd06635 162 GQVKLADFGSASIASPANSFVGTPY-------WMAPEVIlamDEGQYDGKVDVWSLGITCIE-LAERKPPLFNMNAMSAL 233

                ....*..
gi 31455611 550 AFIEQGK 556
Cdd:cd06635 234 YHIAQNE 240
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
321-556 2.39e-13

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 71.21  E-value: 2.39e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 321 DPEElkdKKLFLKRD-NLLIADI-ELGCGNFGSVRQGvYRMRKKQIdVAIKVL----KQGTEKadTEEMMREAQIMHQLD 394
Cdd:cd06634   1 DPEV---AELFFKDDpEKLFSDLrEIGHGSFGAVYFA-RDVRNNEV-VAIKKMsysgKQSNEK--WQDIIKEVKFLQKLR 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 395 NPYIVRLIGVCQAE-ALMLVMEMAGGGPLHKFLVGKR--EEIpvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN 471
Cdd:cd06634  74 HPNTIEYRGCYLREhTAWLVMEYCLGSASDLLEVHKKplQEV---EIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTE 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 472 RHYAKISDFGLSKALGADDSYYTARSagkwplkWYAPECI---NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEV 548
Cdd:cd06634 151 PGLVKLGDFGSASIMAPANSFVGTPY-------WMAPEVIlamDEGQYDGKVDVWSLGITCIE-LAERKPPLFNMNAMSA 222

                ....*...
gi 31455611 549 MAFIEQGK 556
Cdd:cd06634 223 LYHIAQNE 230
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
344-541 2.48e-13

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 70.66  E-value: 2.48e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVL-KQGTEKADTE-EMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGG 420
Cdd:cd14117  14 LGKGKFGNVY--LAREKQSKFIVALKVLfKSQIEKEGVEhQLRREIEIQSHLRHPNILRLYNYFHdRKRIYLILEYAPRG 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAddsyyTARSAGK 500
Cdd:cd14117  92 ELYKEL-QKHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWSVHAPS-----LRRRTMC 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 501 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPYK 541
Cdd:cd14117 166 GTLDYLPPEMIEGRTHDEKVDLWCIGVLCYELL-VGMPPFE 205
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
344-540 2.54e-13

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 70.90  E-value: 2.54e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVL-KQGTEK-ADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd14209   9 LGTGSFGRVM--LVRHKETGNYYAMKILdKQKVVKlKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSnLYMVMEYVPGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFL--VGKREEIPVSNVAEllhQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKalgaddsyytaRSA 498
Cdd:cd14209  87 EMFSHLrrIGRFSEPHARFYAA---QIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAK-----------RVK 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 31455611 499 GK-WPL----KWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPY 540
Cdd:cd14209 153 GRtWTLcgtpEYLAPEIILSKGYNKAVDWWALGVLIYE-MAAGYPPF 198
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
373-540 2.67e-13

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271102 [Multi-domain]  Cd Length: 284  Bit Score: 70.75  E-value: 2.67e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 373 QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA---LMLVMEMAGGGPLHkflvgkreEIP-----VSNVAEL-LH 443
Cdd:cd14200  60 QAKPLAPLERVYQEIAILKKLDHVNIVKLIEVLDDPAednLYMVFDLLRKGPVM--------EVPsdkpfSEDQARLyFR 131
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 444 QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArSAGKwPlKWYAPECI--NFRKFSSRS- 520
Cdd:cd14200 132 DIVLGIEYLHYQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQFEGNDALLSS-TAGT-P-AFMAPETLsdSGQSFSGKAl 208
                       170       180
                ....*....|....*....|
gi 31455611 521 DVWSYGVTMWeALSYGQKPY 540
Cdd:cd14200 209 DVWAMGVTLY-CFVYGKCPF 227
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
338-547 2.87e-13

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 70.01  E-value: 2.87e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 338 LIADIelGCGNFGSVRQgvyrMRKKQID--VAIKVLKQGtEKADtEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVM 414
Cdd:cd14665   4 LVKDI--GSGNFGVARL----MRDKQTKelVAVKYIERG-EKID-ENVQREIINHRSLRHPNIVRFKEVILTPThLAIVM 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFL--VGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA--KISDFGLSKalgADD 490
Cdd:cd14665  76 EYAAGGELFERIcnAGRFSE---DEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAPrlKICDFGYSK---SSV 149
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 491 SYYTARSAGKWPlKWYAPECINFRKFSSR-SDVWSYGVTMWEALsYGQKPYKKMKGPE 547
Cdd:cd14665 150 LHSQPKSTVGTP-AYIAPEVLLKKEYDGKiADVWSCGVTLYVML-VGAYPFEDPEEPR 205
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
343-530 2.95e-13

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 70.53  E-value: 2.95e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKaDTEEMMREAQIMHQLDNPYIVRLIGVCQAEAL-MLVMEMAGGGP 421
Cdd:cd14086   8 ELGKGAFSVVRRCVQKSTGQEFAAKIINTKKLSAR-DHQKLEREARICRLLKHPNIVRLHDSISEEGFhYLVFDLVTGGE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGkREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHY---AKISDFGLS-KALGADDSYYT-AR 496
Cdd:cd14086  87 LFEDIVA-REFYSEADASHCIQQILESVNHCHQNGIVHRDLKPENLLLASKSKgaaVKLADFGLAiEVQGDQQAWFGfAG 165
                       170       180       190
                ....*....|....*....|....*....|....
gi 31455611 497 SAGkwplkWYAPECINFRKFSSRSDVWSYGVTMW 530
Cdd:cd14086 166 TPG-----YLSPEVLRKDPYGKPVDIWACGVILY 194
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
8-105 3.16e-13

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 65.68  E-value: 3.16e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   8 LPFFYGSISRAEAEEHLKLAGMADGLFLLRQcLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFY 87
Cdd:cd10401   3 MPWFHGKISREESEQILLIGSKTNGKFLIRE-RDNNGSYALCLLHDGKVLHYRIDKDKTGKLSIPDGKKFDTLWQLVEHY 81
                        90
                ....*....|....*...
gi 31455611  88 SRDPDGLPCNLRKPCNRP 105
Cdd:cd10401  82 SYKPDGLLRVLTEPCPRI 99
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
343-540 3.20e-13

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 70.00  E-value: 3.20e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADteEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGGP 421
Cdd:cd14113  14 ELGRGRFSVVKKCDQRGTKRA--VATKFVNKKLMKRD--QVTHELGVLQSLQHPQLVGLLDTFEtPTSYILVLEMADQGR 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLV--GKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL---VNRHYAKISDFGlsKALGADDSYYTAR 496
Cdd:cd14113  90 LLDYVVrwGNLTE---EKIRFYLREILEALQYLHNCRIAHLDLKPENILVdqsLSKPTIKLADFG--DAVQLNTTYYIHQ 164
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 497 SAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14113 165 LLGS--PEFAAPEIILGNPVSLTSDLWSIGVLTYVLLS-GVSPF 205
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
344-540 3.21e-13

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270768 [Multi-domain]  Cd Length: 357  Bit Score: 71.59  E-value: 3.21e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVR---QGVY------RMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLD-NPYIVRLIGVCQAEA-L 410
Cdd:cd05617  12 LGLQDFDLIRvigRGSYakvllvRLKKNDQIYAMKVVKKELvhDDEDIDWVQTEKHVFEQASsNPFLVGLHSCFQTTSrL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 411 MLVMEMAGGGPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK-ALGAD 489
Cdd:cd05617  92 FLVIEYVNGGDL-MFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKeGLGPG 170
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 31455611 490 DSyyTARSAGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05617 171 DT--TSTFCGT-P-NYIAPEILRGEEYGFSVDWWALGVLMFEMMA-GRSPF 216
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
345-564 3.97e-13

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270750 [Multi-domain]  Cd Length: 324  Bit Score: 70.72  E-value: 3.97e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 345 GCGNFGSVRqgVYRMRKKQIDVAIKVLKQgtekadtEEMMREAQIMH---------QLDNPYIVRLIGVCQ-AEALMLVM 414
Cdd:cd05599  10 GRGAFGEVR--LVRKKDTGHVYAMKKLRK-------SEMLEKEQVAHvraerdilaEADNPWVVKLYYSFQdEENLYLIM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLVGK---REEIPVSNVAELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADD- 490
Cdd:cd05599  81 EFLPGGDMMTLLMKKdtlTEEETRFYIAETV----LAIESIHKLGYIHRDIKPDNLLLDARGHIKLSDFGLCTGLKKSHl 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTARSAGkwplkWYAPECINFRKFSSRSDVWSYGVTMWEALsYG---------QKPYKK-MKGPEVMAFIEQgkrMEC 560
Cdd:cd05599 157 AYSTVGTPD-----YIAPEVFLQKGYGKECDWWSLGVIMYEML-IGyppfcsddpQETCRKiMNWRETLVFPPE---VPI 227

                ....
gi 31455611 561 PPEC 564
Cdd:cd05599 228 SPEA 231
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
344-562 4.07e-13

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 69.59  E-value: 4.07e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14185   8 IGDGNFAVVK--ECRHWNENQEYAMKIIDKSKLKGKEDMIESEILIIKSLSHPNIVKLFEVYETEKeIYLILEYVRGGDL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNRH-----YAKISDFGLSKAlgADDSYYTARS 497
Cdd:cd14185  86 FDAII-ESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPEN-LLVQHNpdkstTLKLADFGLAKY--VTGPIFTVCG 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 498 AGkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMK--GPEVMAFIEQGKRMECPP 562
Cdd:cd14185 162 TP----TYVAPEILSEKGYGLEVDMWAAGVILYILLC-GFPPFRSPErdQEELFQIIQLGHYEFLPP 223
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
344-539 4.18e-13

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 70.22  E-value: 4.18e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKADTE-EMMREAQIMHQLDNPYIVRLIGVC-----------QAEA 409
Cdd:cd07864  15 IGEGTYGQV----YKAKDKDTGelVALKKVRLDNEKEGFPiTAIREIKILRQLNHRSVVNLKEIVtdkqdaldfkkDKGA 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 LMLVMEMAGG---GPLHKFLVGKREEipvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL 486
Cdd:cd07864  91 FYLVFEYMDHdlmGLLESGLVHFSED----HIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLARLY 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 487 GADDSY-YTARSAGKWplkWYAPE-CINFRKFSSRSDVWSYGVTMWEALSygQKP 539
Cdd:cd07864 167 NSEESRpYTNKVITLW---YRPPElLLGEERYGPAIDVWSCGCILGELFT--KKP 216
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
344-556 4.19e-13

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270779 [Multi-domain]  Cd Length: 285  Bit Score: 70.05  E-value: 4.19e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdVAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGP 421
Cdd:cd05630   8 LGKGGFGEVCACQVRATGKMY-ACKKLEKKRIKKRKGEAMaLNEKQILEKVNSRFVVSLAYAYETkDALCLVLTLMNGGD 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 L--HKFLVGKrEEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYYTARSAg 499
Cdd:cd05630  87 LkfHIYHMGQ-AGFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAVHV-PEGQTIKGRVG- 163
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 31455611 500 kwPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY----KKMKGPEVMAFIEQGK 556
Cdd:cd05630 164 --TVGYMAPEVVKNERYTFSPDWWALGCLLYEMIA-GQSPFqqrkKKIKREEVERLVKEVP 221
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
344-574 4.67e-13

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270765 [Multi-domain]  Cd Length: 332  Bit Score: 70.72  E-value: 4.67e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRK-----KQIDVAIKVLKQGT--EKADTEEMMR-EAQIM-HQLDNPYIVRLIGVCQAEA-LMLV 413
Cdd:cd05614   8 LGTGAYGKV----FLVRKvsghdANKLYAMKVLRKAAlvQKAKTVEHTRtERNVLeHVRQSPFLVTLHYAFQTDAkLHLI 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 414 MEMAGGGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYY 493
Cdd:cd05614  84 LDYVSGGELFTHLY-QRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKEFLTEEKER 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 494 TARSAGKwpLKWYAPECINFRKFSSRS-DVWSYGVTMWEALSyGQKPYkKMKGpEVMAFIEQGKR-MECPPECPPELYAL 571
Cdd:cd05614 163 TYSFCGT--IEYMAPEIIRGKSGHGKAvDWWSLGILMFELLT-GASPF-TLEG-EKNTQSEVSRRiLKCDPPFPSFIGPV 237

                ...
gi 31455611 572 MSD 574
Cdd:cd05614 238 ARD 240
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
162-253 5.25e-13

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 65.30  E-value: 5.25e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 162 PWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQ-GTYALSL-----IYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQL 235
Cdd:cd09933   4 EWFFGKIKRKDAEKLLLAPGNPRGTFLIRESETTpGAYSLSVrdgddARGDTVKHYRIRKLDNGGYYITTRATFPTLQEL 83
                        90
                ....*....|....*...
gi 31455611 236 VEYLKLKADGLIYCLKEA 253
Cdd:cd09933  84 VQHYSKDADGLCCRLTVP 101
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
331-555 5.61e-13

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 70.07  E-value: 5.61e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 331 FLKRDNLLIADIELGCGNFGSVRQGVYRmrKKQIDVAIKVLKQGTEkADTEemmREAQIMHQLD-NPYIVRLIGVCQAEA 409
Cdd:cd14179   2 FYQHYELDLKDKPLGEGSFSICRKCLHK--KTNQEYAVKIVSKRME-ANTQ---REIAALKLCEgHPNIVKLHEVYHDQL 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 -LMLVMEMAGGGPLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH---YAKISDFGLSKA 485
Cdd:cd14179  76 hTFLVMELLKGGELLE-RIKKKQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFTDESdnsEIKIIDFGFARL 154
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 486 LGADDSYYTARSagkWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKK-------MKGPEVMAFIEQG 555
Cdd:cd14179 155 KPPDNQPLKTPC---FTLHYAAPELLNYNGYDESCDLWSLGVILYTMLS-GQVPFQChdksltcTSAEEIMKKIKQG 227
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
344-540 7.03e-13

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270741 [Multi-domain]  Cd Length: 326  Bit Score: 70.02  E-value: 7.03e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQG--TEKADTEEMMREAQIM---HQLDNPYIVRLIGVCQA-EALMLVMEMA 417
Cdd:cd05589   7 LGRGHFGKVLLAEYKPTGEL--FAIKALKKGdiIARDEVESLMCEKRIFetvNSARHPFLVNLFACFQTpEHVCFVMEYA 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPL----HK--FlvgkREEIPVSNVAEllhqVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK-ALGADD 490
Cdd:cd05589  85 AGGDLmmhiHEdvF----SEPRAVFYAAC----VVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKeGMGFGD 156
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SyyTARSAGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05589 157 R--TSTFCGT-P-EFLAPEVLTDTSYTRAVDWWGLGVLIYEML-VGESPF 201
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
343-554 7.06e-13

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 69.02  E-value: 7.06e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGvYRMRKKQIdVAIKVL----KQGTEKadTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMA 417
Cdd:cd06607   8 EIGHGSFGAVYYA-RNKRTSEV-VAIKKMsysgKQSTEK--WQDIIKEVKFLRQLRHPNTIEYKGCYLREhTAWLVMEYC 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGP-----LHKFLVGKREeipvsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGlSKALGAddsy 492
Cdd:cd06607  84 LGSAsdiveVHKKPLQEVE------IAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFG-SASLVC---- 152
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 493 yTARSAGKWPLkWYAPECI---NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIEQ 554
Cdd:cd06607 153 -PANSFVGTPY-WMAPEVIlamDEGQYDGKVDVWSLGITCIE-LAERKPPLFNMNAMSALYHIAQ 214
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
344-585 7.66e-13

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271083 [Multi-domain]  Cd Length: 279  Bit Score: 69.23  E-value: 7.66e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADTEEM-------MREAQIMHQLDN-PYIVRLIGVCQAEALM-LVM 414
Cdd:cd14181  18 IGRGVSSVVRRCVHRHTGQEF--AVKIIEVTAERLSPEQLeevrsstLKEIHILRQVSGhPSIITLIDSYESSTFIfLVF 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLVGK---REEIPVSNVAELLHQVSmgmkYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDS 491
Cdd:cd14181  96 DLMRRGELFDYLTEKvtlSEKETRSIMRSLLEAVS----YLHANNIVHRDLKPENILLDDQLHIKLSDFGFSCHLEPGEK 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 492 YytaRSAGKWPlKWYAPECI------NFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRMECPPEcp 565
Cdd:cd14181 172 L---RELCGTP-GYLAPEILkcsmdeTHPGYGKEVDLWACGVILFTLLA-GSPPFWHRRQMLMLRMIMEGRYQFSSPE-- 244
                       250       260
                ....*....|....*....|
gi 31455611 566 pelyalmsdcwiykWEDRPD 585
Cdd:cd14181 245 --------------WDDRSS 250
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
343-549 7.68e-13

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271020 [Multi-domain]  Cd Length: 275  Bit Score: 69.31  E-value: 7.68e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVR-------QGVYRMR-------KKQIDVAIKVLKQGTEKADT------EEMMREAQIMHQLDNPYIVRLI 402
Cdd:cd14118   1 EIGKGSYGIVKlayneedNTLYAMKilskkklLKQAGFFRRPPPRRKPGALGkpldplDRVYREIAILKKLDHPNVVKLV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 403 GVCQAEA---LMLVMEMAGGGPLhkflvgkREEIPVSNVAE-----LLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHY 474
Cdd:cd14118  81 EVLDDPNednLYMVFELVDKGAV-------MEVPTDNPLSEetarsYFRDIVLGIEYLHYQKIIHRDIKPSNLLLGDDGH 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 475 AKISDFGLSKALGADDSYYTaRSAGKwPlKWYAPECI--NFRKFSSRS-DVWSYGVTMWeALSYGQKP---------YKK 542
Cdd:cd14118 154 VKIADFGVSNEFEGDDALLS-STAGT-P-AFMAPEALseSRKKFSGKAlDIWAMGVTLY-CFVFGRCPfeddhilglHEK 229

                ....*..
gi 31455611 543 MKGPEVM 549
Cdd:cd14118 230 IKTDPVV 236
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
343-540 7.94e-13

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 68.86  E-value: 7.94e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFgSVrqgVYRMRKKQ-ID-VAIKVlkqgTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd14010   7 EIGRGKH-SV---VYKGRRKGtIEfVAIKC----VDKSKRPEVLNEVRLTHELKHPNVLKFYEWYETSNhLWLVVEYCTG 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALG--ADDSYYTARS 497
Cdd:cd14010  79 GDL-ETLLRQDGNLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREGeiLKELFGQFSD 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 31455611 498 AGKWPLK-----------WYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPY 540
Cdd:cd14010 158 EGNVNKVskkqakrgtpyYMAPELFQGGVHSFASDLWALGCVLYE-MFTGKPPF 210
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
343-537 7.98e-13

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 69.27  E-value: 7.98e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKK---QIdVAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMA 417
Cdd:cd07833   8 VVGEGAYGVV----LKCRNKatgEI-VAIKKFKESEDDEDVKKTaLREVKVLRQLRHENIVNLKEAFRRKGrLYLVFEYV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGpLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNRH-YAKISDFGLSKAL-GADDSYYTA 495
Cdd:cd07833  83 ERT-LLELLEASPGGLPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPEN-ILVSESgVLKLCDFGFARALtARPASPLTD 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 496 RSAGKWplkWYAPEC-INFRKFSSRSDVWSYGVTMWEaLSYGQ 537
Cdd:cd07833 161 YVATRW---YRAPELlVGDTNYGKPVDVWAIGCIMAE-LLDGE 199
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
344-556 8.17e-13

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 69.29  E-value: 8.17e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMrkKQIDVAIKVLKQgTEKADTEE---MMREAQimhqldNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:cd14175   9 IGVGSYSVCKRCVHKA--TNMEYAVKVIDK-SKRDPSEEieiLLRYGQ------HPNIITLKDVYdDGKHVYLVTELMRG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPL------HKFLvGKREeipvsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV----NRHYAKISDFGLSKALGAD 489
Cdd:cd14175  80 GELldkilrQKFF-SERE------ASSVLHTICKTVEYLHSQGVVHRDLKPSNILYVdesgNPESLRICDFGFAKQLRAE 152
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 490 DSY-----YTArsagkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKkmKGP-----EVMAFIEQGK 556
Cdd:cd14175 153 NGLlmtpcYTA--------NFVAPEVLKRQGYDEGCDIWSLGILLYTMLA-GYTPFA--NGPsdtpeEILTRIGSGK 218
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
356-533 1.06e-12

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 69.32  E-value: 1.06e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 356 VYRMRKKQID--VAIKVLKQGTEKADTE-EMMREAQIMHQLDNPYIVRLIGVC---QAEALMLVMEMAGGGpLHKFLVGK 429
Cdd:cd07845  23 VYRARDTTSGeiVALKKVRMDNERDGIPiSSLREITLLLNLRHPNIVELKEVVvgkHLDSIFLVMEYCEQD-LASLLDNM 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 430 REEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKWplkWYAPE 509
Cdd:cd07845 102 PTPFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYGLPAKPMTPKVVTLW---YRAPE 178
                       170       180
                ....*....|....*....|....*
gi 31455611 510 CI-NFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd07845 179 LLlGCTTYTTAIDMWAVGCILAELL 203
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
343-540 1.06e-12

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 68.73  E-value: 1.06e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIdvAIKVLKqgTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGP 421
Cdd:cd14104   7 ELGRGQFGIVHRCVETSSKKTY--MAKFVK--VKGADQVLVKKEISILNIARHRNILRLHESFEShEELVMIFEFISGVD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNR--HYAKISDFGLSKALGADDSY---YTAR 496
Cdd:cd14104  83 IFERITTARFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTRrgSYIKIIEFGQSRQLKPGDKFrlqYTSA 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 497 sagkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14104 163 -------EFYAPEVHQHESVSTATDMWSLGCLVYVLLS-GINPF 198
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
344-533 1.10e-12

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 69.00  E-value: 1.10e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRmRKKQIDVAIKVLK---------QGTEKADTeemMREAQIMHQLDNPYIVRLIGVCQ-AEALMLV 413
Cdd:cd14096   9 IGEGAFSNVYKAVPL-RNTGKPVAIKVVRkadlssdnlKGSSRANI---LKEVQIMKRLSHPNIVKLLDFQEsDEYYYIV 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 414 MEMAGGGPL-HKFlvgkreeIPVSNVAELL--H---QVSMGMKYLEEKNFVHRDLAARNVLL--------VNRHY----- 474
Cdd:cd14096  85 LELADGGEIfHQI-------VRLTYFSEDLsrHvitQVASAVKYLHEIGVVHRDIKPENLLFepipfipsIVKLRkaddd 157
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 475 --------------------AKISDFGLSKALGADDSYYTARSAGkwplkWYAPECINFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd14096 158 etkvdegefipgvggggigiVKLADFGLSKQVWDSNTKTPCGTVG-----YTAPEVVKDERYSKKVDMWALGCVLYTLL 231
STKc_LATS cd05598
Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the ...
344-540 1.28e-12

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270749 [Multi-domain]  Cd Length: 333  Bit Score: 69.27  E-value: 1.28e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDV--AIKVLKqgteKADTeeMMR--------EAQIMHQLDNPYIVRLIGVCQ-AEALML 412
Cdd:cd05598   9 IGVGAFGEV----SLVRKKDTNAlyAMKTLR----KKDV--LKRnqvahvkaERDILAEADNEWVVKLYYSFQdKENLYF 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 413 VMEMAGGGPLHKFLVGK---REEIPVSNVAELLhqvsMGMKYLEEKNFVHRDLAARNVlLVNRH-YAKISDFGLSKAL-- 486
Cdd:cd05598  79 VMDYIPGGDLMSLLIKKgifEEDLARFYIAELV----CAIESVHKMGFIHRDIKPDNI-LIDRDgHIKLTDFGLCTGFrw 153
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 31455611 487 GADDSYYTARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05598 154 THDSKYYLAHSLVGTP-NYIAPEVLLRTGYTQLCDWWSVGVILYEML-VGQPPF 205
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
344-594 1.33e-12

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 68.39  E-value: 1.33e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGnfGSVRqgVYRMR--KKQIdVAIKVLK-QGTEKADTEEMMREAQIMHQL-DNPYIVRLIG--VCQAEALM-LVMEM 416
Cdd:cd14131   9 LGKG--GSSK--VYKVLnpKKKI-YALKRVDlEGADEQTLQSYKNEIELLKKLkGSDRIIQLYDyeVTDEDDYLyMVMEC 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 aGGGPLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYaKISDFGLSKALgADDSYYTA 495
Cdd:cd14131  84 -GEIDLATILKKKRPKpIDPNFIRYYWKQMLEAVHTIHEEGIVHSDLKPANFLLVKGRL-KLIDFGIAKAI-QNDTTSIV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWPLKWYAPECI----------NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGP--EVMAFIEQGKRMECPPE 563
Cdd:cd14131 161 RDSQVGTLNYMSPEAIkdtsasgegkPKSKIGRPSDVWSLGCILYQ-MVYGKTPFQHITNPiaKLQAIIDPNHEIEFPDI 239
                       250       260       270
                ....*....|....*....|....*....|.
gi 31455611 564 CPPELYALMSDCWIYKWEDRPdflTVEQRMR 594
Cdd:cd14131 240 PNPDLIDVMKRCLQRDPKKRP---SIPELLN 267
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
344-531 1.57e-12

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271035 [Multi-domain]  Cd Length: 262  Bit Score: 68.06  E-value: 1.57e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKqiDVAIKVLKQGTEKADTEemMREAQIMHQL------DNPYIVRLIGVCQ-AEALMLVMEM 416
Cdd:cd14133   7 LGKGTFGQVVKCYDLLTGE--EVALKIIKNNKDYLDQS--LDEIRLLELLnkkdkaDKYHIVRLKDVFYfKNHLCIVFEL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGpLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN--RHYAKISDFG----LSKALGad 489
Cdd:cd14133  83 LSQN-LYEFLKQNKFQyLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLASysRCQIKIIDFGsscfLTQRLY-- 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 31455611 490 dSYYTARSagkwplkWYAPECINFRKFSSRSDVWSYGVTMWE 531
Cdd:cd14133 160 -SYIQSRY-------YRAPEVILGLPYDEKIDMWSLGCILAE 193
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
344-541 1.61e-12

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 68.10  E-value: 1.61e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGPL 422
Cdd:cd14183  14 IGDGNFAVVKECVERSTGRE--YALKIINKSKCRGKEHMIQNEVSILRRVKHPNIVLLIEEMDMpTELYLVMELVKGGDL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNRHY-----AKISDFGLSKALgaDDSYYTARS 497
Cdd:cd14183  92 FDAITSTNKYTE-RDASGMLYNLASAIKYLHSLNIVHRDIKPEN-LLVYEHQdgsksLKLGDFGLATVV--DGPLYTVCG 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 498 AGkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYK 541
Cdd:cd14183 168 TP----TYVAPEIIAETGYGLKVDIWAAGVITYILLC-GFPPFR 206
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
365-540 1.74e-12

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 68.60  E-value: 1.74e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 365 DVAIKVLKQgTEKADTEEMMREAQIMHQLDNPYIVRLI-GVCQAEALMLVMEMAGGGPLHKflVGKREEIPVSNVAELLH 443
Cdd:cd06655  46 EVAIKQINL-QKQPKKELIINEILVMKELKNPNIVNFLdSFLVGDELFVVMEYLAGGSLTD--VVTETCMDEAQIAAVCR 122
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 444 QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyytARSAGKWPLKWYAPECINFRKFSSRSDVW 523
Cdd:cd06655 123 ECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQS---KRSTMVGTPYWMAPEVVTRKAYGPKVDIW 199
                       170
                ....*....|....*..
gi 31455611 524 SYGVTMWEALSyGQKPY 540
Cdd:cd06655 200 SLGIMAIEMVE-GEPPY 215
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
344-540 1.76e-12

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271068 [Multi-domain]  Cd Length: 285  Bit Score: 68.10  E-value: 1.76e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGTEKADTEeMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14166  11 LGSGAFSEVY--LVKQRSTGKLYALKCIKKSPLSRDSS-LENEIAVLKRIKHENIVTLEDIYESTThYYLVMQLVSGGEL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLV--GKREEIPVSNVaelLHQVSMGMKYLEEKNFVHRDLAARNVL-LVNRHYAK--ISDFGLSKalgADDSYYTARS 497
Cdd:cd14166  88 FDRILerGVYTEKDASRV---INQVLSAVKYLHENGIVHRDLKPENLLyLTPDENSKimITDFGLSK---MEQNGIMSTA 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 498 AGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14166 162 CGT-P-GYVAPEVLAQKPYSKAVDCWSIGVITYILLC-GYPPF 201
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
344-540 1.82e-12

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270996 [Multi-domain]  Cd Length: 300  Bit Score: 68.34  E-value: 1.82e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKA--DTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd14094  11 IGKGPFSVVRRCIHRETGQQFAVKIVDVAKFTSSPglSTEDLKREASICHMLKHPHIVELLETYSSDGmLYMVFEFMDGA 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLV---NRHYAKISDFGLSKALGADDSYYT 494
Cdd:cd14094  91 DLCFEIVKRADAGFVYSEAVASHymrQILEALRYCHDNNIIHRDVKPHCVLLAskeNSAPVKLGGFGVAIQLGESGLVAG 170
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 31455611 495 ARSAGKwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14094 171 GRVGTP---HFMAPEVVKREPYGKPVDVWGCGVILFILLS-GCLPF 212
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
9-101 1.87e-12

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 63.68  E-value: 1.87e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIeRQL-NGTYAIAGGKAHCGPAELCEFY 87
Cdd:cd10370   4 PWYFGKIKRIEAEKKLLLPENEHGAFLIRDSESRHNDYSLSVRDGDTVKHYRI-RQLdEGGFFIARRTTFRTLQELVEHY 82
                        90
                ....*....|....
gi 31455611  88 SRDPDGLPCNLRKP 101
Cdd:cd10370  83 SKDSDGLCVNLRKP 96
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
344-532 1.93e-12

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 67.83  E-value: 1.93e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdVAIKVLKQGTEKA-DTEEMMREAQIMHQLDN---PYIVRLIGVCQAEA-LMLVMEMAG 418
Cdd:cd14052   8 IGSGEFSQVYKVSERVPTGKV-YAVKKLKPNYAGAkDRLRRLEEVSILRELTLdghDNIVQLIDSWEYHGhLYIQTELCE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFL--VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYytar 496
Cdd:cd14052  87 NGSLDVFLseLGLLGRLDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVWPLIRGI---- 162
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 31455611 497 sAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEA 532
Cdd:cd14052 163 -EREGDREYIAPEILSEHMYDKPADIFSLGLILLEA 197
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
344-584 1.95e-12

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270858 [Multi-domain]  Cd Length: 256  Bit Score: 67.53  E-value: 1.95e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVA-IKVLKQgtEKADTEEMMREAQIMHQLDNPYIVRLI-GVCQAEALMLVMEMAGGGP 421
Cdd:cd08218   8 IGEGSFGKALLVKSKEDGKQYVIKeINISKM--SPKEREESRKEVAVLSKMKHPNIVQYQeSFEENGNLYIVMDYCDGGD 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKRE-EIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAGK 500
Cdd:cd08218  86 LYKRINAQRGvLFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVL--NSTVELARTCIG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSYgQKPYK--KMKGpeVMAFIEQGKRMECPPECPPELYALMSDCWIY 578
Cdd:cd08218 164 TPY-YLSPEICENKPYNNKSDIWALGCVLYEMCTL-KHAFEagNMKN--LVLKIIRGSYPPVPSRYSYDLRSLVSQLFKR 239

                ....*.
gi 31455611 579 KWEDRP 584
Cdd:cd08218 240 NPRDRP 245
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
344-544 2.09e-12

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270780 [Multi-domain]  Cd Length: 313  Bit Score: 68.46  E-value: 2.09e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAiKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGP 421
Cdd:cd05632  10 LGKGGFGEVCACQVRATGKMYACK-RLEKKRIKKRKGESMaLNEKQILEKVNSQFVVNLAYAYETkDALCLVLTIMNGGD 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LhKFLV------GKREEIPVSNVAELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd05632  89 L-KFHIynmgnpGFEEERALFYAAEIL----CGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKIPEGESIRGR 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 496 RSAgkwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMK 544
Cdd:cd05632 164 VGT----VGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIE-GQSPFRGRK 207
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
344-533 2.11e-12

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 67.64  E-value: 2.11e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLK--QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd05572   1 LGVGGFGRVE--LVQLKSKGRTFALKCVKkrHIVQTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKyLYMLMEYCLGG 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLvgkREEIPVSNVAE--LLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArsA 498
Cdd:cd05572  79 ELWTIL---RDRGLFDEYTArfYTACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGSGRKTWTF--C 153
                       170       180       190
                ....*....|....*....|....*....|....*
gi 31455611 499 GKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd05572 154 GT--PEYVAPEIILNKGYDFSVDYWSLGILLYELL 186
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
343-616 2.15e-12

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270852 [Multi-domain]  Cd Length: 286  Bit Score: 68.06  E-value: 2.15e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGp 421
Cdd:cd07870   7 KLGEGSYATVYKGISRINGQL--VALKVISMKTEEGVPFTAIREASLLKGLKHANIVLLHDIIHTkETLTFVFEYMHTD- 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAgkw 501
Cdd:cd07870  84 LAQYMIQHPGGLHPYNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLARAKSIPSQTYSSEVV--- 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 pLKWYAPE--CINFRKFSSRSDVWSYGVTMWEALSyGQKPYkkmkgPEVMAFIEQGKRMECPPECPPElyalmsDCW--- 576
Cdd:cd07870 161 -TLWYRPPdvLLGATDYSSALDIWGAGCIFIEMLQ-GQPAF-----PGVSDVFEQLEKIWTVLGVPTE------DTWpgv 227
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 31455611 577 ---------IYKWEDRPDFLTVEQRMRACYYS--LASKV--EGPPGSTQKAEA 616
Cdd:cd07870 228 sklpnykpeWFLPCKPQQLRVVWKRLSRPPKAedLASQMlmMFPKDRISAQDA 280
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
356-534 2.25e-12

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 68.02  E-value: 2.25e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 356 VYRMRKKQID--VAIKVLKQGTEKAD---TEemMREAQIMHQLDNPYIVRligvcqaealmlVMEMAGGGPLHK-FLV-- 427
Cdd:cd07843  21 VYRARDKKTGeiVALKKLKMEKEKEGfpiTS--LREINILLKLQHPNIVT------------VKEVVVGSNLDKiYMVme 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 428 -----------GKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLskalgaddsyytAR 496
Cdd:cd07843  87 yvehdlkslmeTMKQPFLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGL------------AR 154
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 497 SAGKwPLK---------WY-APECI-NFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07843 155 EYGS-PLKpytqlvvtlWYrAPELLlGAKEYSTAIDMWSVGCIFAELLT 202
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
344-534 2.25e-12

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 67.41  E-value: 2.25e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKqIDVAIKVLKQGTEK----ADTEEMMREAQIMHQL-DNPYIVRLIGVC-QAEALMLVMEMA 417
Cdd:cd13997   8 IGSGSFSEV----FKVRSK-VDGCLYAVKKSKKPfrgpKERARALREVEAHAALgQHPNIVRYYSSWeEGGHLYIQMELC 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLvgkREEIPVSNVAE-----LLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAL--GADD 490
Cdd:cd13997  83 ENGSLQDAL---EELSPISKLSEaevwdLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLetSGDV 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 491 SYYTARsagkwplkWYAPECIN-FRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd13997 160 EEGDSR--------YLAPELLNeNYTHLPKADIFSLGVTVYEAAT 196
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
343-556 2.30e-12

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 68.51  E-value: 2.30e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmrKKQIDVAIKVLKQgTEKADTEE---MMREAQimhqldNPYIVRLIGVCQ-AEALMLVME-MA 417
Cdd:cd14176  26 DIGVGSYSVCKRCIHK--ATNMEFAVKIIDK-SKRDPTEEieiLLRYGQ------HPNIITLKDVYDdGKYVYVVTElMK 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV----NRHYAKISDFGLSKALGADDSY- 492
Cdd:cd14176  97 GGELLDKIL--RQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVdesgNPESIRICDFGFAKQLRAENGLl 174
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611 493 ----YTArsagkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKkmKGP-----EVMAFIEQGK 556
Cdd:cd14176 175 mtpcYTA--------NFVAPEVLERQGYDAACDIWSLGVLLYTMLT-GYTPFA--NGPddtpeEILARIGSGK 236
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
365-540 2.67e-12

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 67.26  E-value: 2.67e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 365 DVAIKV--LKQGTEKadtEEMMREAQIMHQLDNPYIVRLIG---VCqaEALMLVMEMAGGGPLHKflVGKREEIPVSNVA 439
Cdd:cd06647  34 EVAIKQmnLQQQPKK---ELIINEILVMRENKNPNIVNYLDsylVG--DELWVVMEYLAGGSLTD--VVTETCMDEGQIA 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 440 ELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKWplkWYAPECINFRKFSSR 519
Cdd:cd06647 107 AVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPY---WMAPEVVTRKAYGPK 183
                       170       180
                ....*....|....*....|.
gi 31455611 520 SDVWSYGVTMWEALSyGQKPY 540
Cdd:cd06647 184 VDIWSLGIMAIEMVE-GEPPY 203
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
343-526 2.74e-12

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 67.83  E-value: 2.74e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmRKKQIdVAIKVLK-QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd07861   7 KIGEGTYGVVYKGRNK-KTGQI-VAMKKIRlESEEEGVPSTAIREISLLKELQHPNIVCLEDVLMQENrLYLVFEFLSMD 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 pLHKFL--VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSA 498
Cdd:cd07861  85 -LKKYLdsLPKGKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAFGIPVRVYTHEVV 163
                       170       180
                ....*....|....*....|....*....
gi 31455611 499 GKWplkWYAPECI-NFRKFSSRSDVWSYG 526
Cdd:cd07861 164 TLW---YRAPEVLlGSPRYSTPVDIWSIG 189
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
345-584 2.97e-12

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 67.33  E-value: 2.97e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 345 GCGNFGSVRQGV-----YRMRKKQIdvAIKVLKQGTEKADTEEMMreaqIMHQLDNPYIVRLIGV-CQAEALMLVMEMAG 418
Cdd:cd06626   9 GEGTFGKVYTAVnldtgELMAMKEI--RFQDNDPKTIKEIADEMK----VLEGLDHPNLVRYYGVeVHREEVYIFMEYCQ 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFL-VGKREEIPVsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGA-DDSYYTAR 496
Cdd:cd06626  83 EGTLEELLrHGRILDEAV--IRVYTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLKNnTTTMAPGE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 497 SAGKWPLKWY-APECINFRKFSSR---SDVWSYGVTMWEALSyGQKPYKKMKGP-EVMAFIEQGkrmeCPPECPPEL--- 568
Cdd:cd06626 161 VNSLVGTPAYmAPEVITGNKGEGHgraADIWSLGCVVLEMAT-GKRPWSELDNEwAIMYHVGMG----HKPPIPDSLqls 235
                       250
                ....*....|....*....
gi 31455611 569 ---YALMSDCWIYKWEDRP 584
Cdd:cd06626 236 pegKDFLSRCLESDPKKRP 254
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
344-539 3.72e-12

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270828 [Multi-domain]  Cd Length: 329  Bit Score: 67.94  E-value: 3.72e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKA-DTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM------LVMEM 416
Cdd:cd07834   8 IGSGAYGVVCSAYDKRTGRK--VAIKKISNVFDDLiDAKRILREIKILRHLKHENIIGLLDILRPPSPEefndvyIVTEL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGpLHKFLvgkREEIPVSN--VAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNRH-YAKISDFGLSKALGADDS-- 491
Cdd:cd07834  86 METD-LHKVI---KSPQPLTDdhIQYFLYQILRGLKYLHSAGVIHRDLKPSN-ILVNSNcDLKICDFGLARGVDPDEDkg 160
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 31455611 492 ----YYTARsagkwplkWY-APECI-NFRKFSSRSDVWSYGVTMWEALsyGQKP 539
Cdd:cd07834 161 flteYVVTR--------WYrAPELLlSSKKYTKAIDIWSVGCIFAELL--TRKP 204
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
343-546 4.02e-12

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 66.72  E-value: 4.02e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgvyrMRKKQID--VAIKVLKQGtEKADtEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:cd14662   7 DIGSGNFGVARL----MRNKETKelVAVKYIERG-LKID-ENVQREIINHRSLRHPNIIRFKEVVlTPTHLAIVMEYAAG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFL--VGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA--KISDFGLSKalgADDSYYTA 495
Cdd:cd14662  81 GELFERIcnAGRFSE---DEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAPrlKICDFGYSK---SSVLHSQP 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 31455611 496 RSAGKWPlKWYAPECINFRKFSSR-SDVWSYGVTMWEALsYGQKPYKKMKGP 546
Cdd:cd14662 155 KSTVGTP-AYIAPEVLSRKEYDGKvADVWSCGVTLYVML-VGAYPFEDPDDP 204
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
343-552 4.36e-12

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 67.34  E-value: 4.36e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGG 419
Cdd:cd07873   9 KLGEGTYATV----YKGRSKLTDnlVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIIHTEkSLTLVFEYLDK 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GpLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlgadDSYYTARSAG 499
Cdd:cd07873  85 D-LKQYLDDCGNSINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARA----KSIPTKTYSN 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 500 KWPLKWYAPECI--NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFI 552
Cdd:cd07873 160 EVVTLWYRPPDIllGSTDYSTQIDMWGVGCIFYE-MSTGRPLFPGSTVEEQLHFI 213
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
353-590 4.96e-12

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 66.83  E-value: 4.96e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 353 RQGVYRMRKKQIDVAIKVLK--QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALML-VMEMAGGGPLHKFLVGK 429
Cdd:cd14044  18 RDSIQRLRQGKYDKKVVILKdlKNNEGNFTEKQKIELNKLLQIDYYNLTKFYGTVKLDTMIFgVIEYCERGSLRDVLNDK 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 430 RE---------EIPVSnvaeLLHQVSMGMKYLEEKNF-VHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYytarsag 499
Cdd:cd14044  98 ISypdgtfmdwEFKIS----VMYDIAKGMSYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFGCNSILPPSKDL------- 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 500 kwplkWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYK-----------KMKGPEVMAFIEQGKRMECPPECPPEL 568
Cdd:cd14044 167 -----WTAPEHLRQAGTSQKGDVYSYGIIAQEIILRKETFYTaacsdrkekiyRVQNPKGMKPFRPDLNLESAGEREREV 241
                       250       260
                ....*....|....*....|..
gi 31455611 569 YALMSDCWIYKWEDRPDFLTVE 590
Cdd:cd14044 242 YGLVKNCWEEDPEKRPDFKKIE 263
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
344-541 5.31e-12

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270726 [Multi-domain]  Cd Length: 316  Bit Score: 67.26  E-value: 5.31e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDV--AIKVLkqgtekaDTEEMMR---------EAQIMHQLDNPYIVRLIGVCQAEA-LM 411
Cdd:cd05574   9 LGKGDVGRV----YLVRLKGTGKlfAMKVL-------DKEEMIKrnkvkrvltEREILATLDHPFLPTLYASFQTSThLC 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 412 LVMEMAGGGPLHKFLV---GKReeIPVSNV----AELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK 484
Cdd:cd05574  78 FVMDYCPGGELFRLLQkqpGKR--LPEEVArfyaAEVL----LALEYLHLLGFVYRDLKPENILLHESGHIMLTDFDLSK 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 485 ALGADDSYYTARSAGKWPLK--------------------------WYAPECINFRKFSSRSDVWSYGVTMWEALsYGQK 538
Cdd:cd05574 152 QSSVTPPPVRKSLRKGSRRSsvksieketfvaepsarsnsfvgteeYIAPEVIKGDGHGSAVDWWTLGILLYEML-YGTT 230

                ...
gi 31455611 539 PYK 541
Cdd:cd05574 231 PFK 233
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
381-540 5.38e-12

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271101 [Multi-domain]  Cd Length: 286  Bit Score: 66.91  E-value: 5.38e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 381 EEMMREAQIMHQLDNPYIVRLIGVC---QAEALMLVMEMAGGGPLHKFLVGKreeiPVS-NVAELLHQ-VSMGMKYLEEK 455
Cdd:cd14199  70 ERVYQEIAILKKLDHPNVVKLVEVLddpSEDHLYMVFELVKQGPVMEVPTLK----PLSeDQARFYFQdLIKGIEYLHYQ 145
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 456 NFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKwplKWYAPECIN-FRK-FSSRS-DVWSYGVTMWeA 532
Cdd:cd14199 146 KIIHRDVKPSNLLVGEDGHIKIADFGVSNEFEGSDALLTNTVGTP---AFMAPETLSeTRKiFSGKAlDVWAMGVTLY-C 221

                ....*...
gi 31455611 533 LSYGQKPY 540
Cdd:cd14199 222 FVFGQCPF 229
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
157-240 6.47e-12

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 61.77  E-value: 6.47e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 157 AHERMPWYHSSLTREEAERKLysgaQTDGKFLLR----PRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIpEGTKFDTL 232
Cdd:cd10361   2 DLENEPYYHGLLPREDAEELL----KNDGDFLVRktepKGGGKRKLVLSVRWDGKIRHFVINRDDGGKYYI-EGKSFKSI 76

                ....*...
gi 31455611 233 WQLVEYLK 240
Cdd:cd10361  77 SELINYYQ 84
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
344-541 6.79e-12

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271086 [Multi-domain]  Cd Length: 259  Bit Score: 66.21  E-value: 6.79e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14184   9 IGDGNFAVVKECVERSTGKEF--ALKIIDKAKCCGKEHLIENEVSILRRVKHPNIIMLIEEMDTPAeLYLVMELVKGGDL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVnrHYA------KISDFGLSKALgaDDSYYTAR 496
Cdd:cd14184  87 FDAITSSTKYTE-RDASAMVYNLASALKYLHGLCIVHRDIKPENLLVC--EYPdgtkslKLGDFGLATVV--EGPLYTVC 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 497 SAGkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYK 541
Cdd:cd14184 162 GTP----TYVAPEIIAETGYGLKVDIWAAGVITYILLC-GFPPFR 201
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
344-533 7.92e-12

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143356 [Multi-domain]  Cd Length: 343  Bit Score: 66.93  E-value: 7.92e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVyrMRKKQIDVAIKVLKQGTEKA-DTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALM------LVME 415
Cdd:cd07851  23 VGSGAYGQVCSAF--DTKTGRKVAIKKLSRPFQSAiHAKRTYRELRLLKHMKHENVIGLLDVfTPASSLEdfqdvyLVTH 100
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGpLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNRHYA-KISDFGLSKALGADDSYYT 494
Cdd:cd07851 101 LMGAD-LNNIV--KCQKLSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSN-LAVNEDCElKILDFGLARHTDDEMTGYV 176
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 495 ARsagkwplKWY-APECI-NFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd07851 177 AT-------RWYrAPEIMlNWMHYNQTVDIWSVGCIMAELL 210
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
343-556 8.18e-12

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 66.19  E-value: 8.18e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMrkKQIDVAIKVLKQgTEKADTEE---MMREAQimhqldNPYIVRLIGVCQ-AEALMLVME-MA 417
Cdd:cd14178  10 DIGIGSYSVCKRCVHKA--TSTEYAVKIIDK-SKRDPSEEieiLLRYGQ------HPNIITLKDVYDdGKFVYLVMElMR 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV----NRHYAKISDFGLSKALGADDSY- 492
Cdd:cd14178  81 GGELLDRIL--RQKCFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNILYMdesgNPESIRICDFGFAKQLRAENGLl 158
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611 493 ----YTArsagkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKkmKGP-----EVMAFIEQGK 556
Cdd:cd14178 159 mtpcYTA--------NFVAPEVLKRQGYDAACDIWSLGILLYTMLA-GFTPFA--NGPddtpeEILARIGSGK 220
STKc_MRCK_alpha cd05623
Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 ...
307-540 8.95e-12

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.


Pssm-ID: 270773 [Multi-domain]  Cd Length: 409  Bit Score: 67.35  E-value: 8.95e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 307 PMPMDTSVYES-PYSDPEELKDKKLFLKRDNLLIADIeLGCGNFGSVrqGVYRMRKKQIDVAIKVLK--QGTEKADTEEM 383
Cdd:cd05623  43 PLRREKNILEYlEWAKPFTSKVKQMRLHKEDFEILKV-IGRGAFGEV--AVVKLKNADKVFAMKILNkwEMLKRAETACF 119
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 384 MREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDL 462
Cdd:cd05623 120 REERDVLVNGDSQWITTLHYAFQDDNnLYLVMDYYVGGDLLTLLSKFEDRLPEDMARFYLAEMVLAIDSVHQLHYVHRDI 199
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 463 AARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKwPlKWYAPECINFR-----KFSSRSDVWSYGVTMWEALsYGQ 537
Cdd:cd05623 200 KPDNILMDMNGHIRLADFGSCLKLMEDGTVQSSVAVGT-P-DYISPEILQAMedgkgKYGPECDWWSLGVCMYEML-YGE 276

                ...
gi 31455611 538 KPY 540
Cdd:cd05623 277 TPF 279
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
344-544 9.04e-12

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270729 [Multi-domain]  Cd Length: 278  Bit Score: 66.01  E-value: 9.04e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVL-KQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAG 418
Cdd:cd05577   1 LGRGGFGEV----CACQVKATGkmYACKKLdKKRIKKKKGETMaLNEKIILEKVSSPFIVSLAYAFETkDKLCLVLTLMN 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPL--HKFLVGKREeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTAR 496
Cdd:cd05577  77 GGDLkyHIYNVGTRG-FSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAVEFKGGKK--IKG 153
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 497 SAGKwpLKWYAPECI-NFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMK 544
Cdd:cd05577 154 RVGT--HGYMAPEVLqKEVAYDFSVDWFALGCMLYEMIA-GRSPFRQRK 199
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
343-544 9.26e-12

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 66.66  E-value: 9.26e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIK-VLKQGTEKADTEEMMREAQIMHQLDN-PYIVRLIGV-----CQAEALMLVME 415
Cdd:cd07857   7 ELGQGAYGIVCSARNAETSEEETVAIKkITNVFSKKILAKRALRELKLLRHFRGhKNITCLYDMdivfpGNFNELYLYEE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGpLHKFLvgkREEIPVSN--VAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNRHYA-KISDFGLSKALGAD--- 489
Cdd:cd07857  87 LMEAD-LHQII---RSGQPLTDahFQSFIYQILCGLKYIHSANVLHRDLKPGN-LLVNADCElKICDFGLARGFSENpge 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 490 -DSYYTARSAGKWplkWYAPEC-INFRKFSSRSDVWSYGVTMWEALsyGQKPYKKMK 544
Cdd:cd07857 162 nAGFMTEYVATRW---YRAPEImLSFQSYTKAIDVWSVGCILAELL--GRKPVFKGK 213
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
344-545 1.07e-11

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270991 [Multi-domain]  Cd Length: 263  Bit Score: 65.39  E-value: 1.07e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgVYRmRKKQIDVAIKVLKqgtekaDTEEMMREAQIMHQLDN-PYIVRLIGV-----CQAEALMLVMEMA 417
Cdd:cd14089   9 LGLGINGKVLE-CFH-KKTGEKFALKVLR------DNPKARREVELHWRASGcPHIVRIIDVyentyQGRKCLLVVMECM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPL-HKFlvGKREEIPVS--NVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA---KISDFGLSKALGADDS 491
Cdd:cd14089  81 EGGELfSRI--QERADSAFTerEAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSKGPNailKLTDFGFAKETTTKKS 158
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31455611 492 --------YYTArsagkwplkwyaPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKG 545
Cdd:cd14089 159 lqtpcytpYYVA------------PEVLGPEKYDKSCDMWSLGVIMYILLC-GYPPFYSNHG 207
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
163-250 1.20e-11

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 61.61  E-value: 1.20e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQTDGKFLLRPRKE-QGTYALSL-----IYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLV 236
Cdd:cd10419   5 WYFGKLGRKDAERQLLSFGNPRGTFLIRESETtKGAYSLSIrdwddMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....
gi 31455611 237 EYLKLKADGLIYCL 250
Cdd:cd10419  85 QHYSEKADGLCFNL 98
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
344-540 1.26e-11

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270754 [Multi-domain]  Cd Length: 321  Bit Score: 66.15  E-value: 1.26e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgvyrMRKKQID---VAIKVLKQGT--EKADTEEMMREAQIM-HQLDNPYIVRLIGVCQ-AEALMLVMEM 416
Cdd:cd05603   3 IGKGSFGKVL-----LAKRKCDgkfYAVKVLQKKTilKKKEQNHIMAERNVLlKNLKHPFLVGLHYSFQtSEKLYFVLDY 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLhkFLVGKREEIPVSNVAELLH-QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlGADDSYYTA 495
Cdd:cd05603  78 VNGGEL--FFHLQRERCFLEPRARFYAaEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCKE-GMEPEETTS 154
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 496 RSAGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05603 155 TFCGT-P-EYLAPEVLRKEPYDRTVDWWCLGAVLYEML-YGLPPF 196
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
365-540 1.32e-11

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 67.51  E-value: 1.32e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  365 DVAIKVLKqgTEKADTEEMM----REAQIMHQLDNPYIVRLIGVCQAEAL-MLVMEMAGGGPLHKFLvgkREE--IPVSN 437
Cdd:NF033483  34 DVAVKVLR--PDLARDPEFVarfrREAQSAASLSHPNIVSVYDVGEDGGIpYIVMEYVDGRTLKDYI---REHgpLSPEE 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  438 VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTAR---SAGkwplkwY-APECINF 513
Cdd:NF033483 109 AVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSTTMTQTNSvlgTVH------YlSPEQARG 182
                        170       180
                 ....*....|....*....|....*..
gi 31455611  514 RKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:NF033483 183 GTVDARSDIYSLGIVLYEMLT-GRPPF 208
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
9-104 1.34e-11

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 61.67  E-value: 1.34e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGT---YAIAGGKAHCGP-AELC 84
Cdd:cd09944   6 PWFHGGISRDEAARLIRQQGLVDGVFLVRESQSNPGAFVLSLKHGQKIKHYQIIPIEDEGqwyFTLDDGVTKFYDlLQLV 85
                        90       100
                ....*....|....*....|
gi 31455611  85 EFYSRDPDGLPCNLRKPCNR 104
Cdd:cd09944  86 EFYQLNAGSLPTRLKHYCTR 105
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
163-255 1.40e-11

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 61.17  E-value: 1.40e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQTDGKFLLRPRKE-QGTYALSL-----IYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLV 236
Cdd:cd10418   5 WYFGKLGRKDAERQLLSFGNPRGTFLIRESETtKGAYSLSIrdwddMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....*....
gi 31455611 237 EYLKLKADGLiyCLKEACP 255
Cdd:cd10418  85 QHYSERAAGL--CCRLVVP 101
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
163-250 1.59e-11

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 61.20  E-value: 1.59e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQTDGKFLLRPRKE-QGTYALSL-----IYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLV 236
Cdd:cd10368   5 WYFGKLGRKDAERQLLSFGNPRGTFLIRESETtKGAYSLSIrdwddMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....
gi 31455611 237 EYLKLKADGLIYCL 250
Cdd:cd10368  85 QHYSETANGLCKVL 98
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
162-238 1.64e-11

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 60.75  E-value: 1.64e-11
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 162 PWYHSSLTREEAERKLySGAQTDGKFLLRpRKEQ--GTYALSLIYGKTVYHYLISQDKAGKYCIPEgTKFDTLWQLVEY 238
Cdd:cd09941   4 PWFHGKISRAEAEEIL-MNQRPDGAFLIR-ESESspGDFSLSVKFGNDVQHFKVLRDGAGKYFLWV-VKFNSLNELVDY 79
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
158-254 1.74e-11

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 61.10  E-value: 1.74e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 158 HERMPWYHSSLTREEAERKLYSGAQTDGKFLLR-----PRkeqgTYALSLIYGKTVYHYLI---SQDKAGKYCIPEG-TK 228
Cdd:cd10414   2 HRSQPWFHHKISRDEAQRLIIQQGLVDGVFLVRdsqsnPR----TFVLSMSHGQKIKHFQIipvEDDGELFHTLDDGhTR 77
                        90       100
                ....*....|....*....|....*..
gi 31455611 229 FDTLWQLVEYLKLKAdGLIYC-LKEAC 254
Cdd:cd10414  78 FTDLIQLVEFYQLNK-GVLPCkLKHYC 103
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
346-594 1.79e-11

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 64.92  E-value: 1.79e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 346 CGNFGSVRQGVYRMRKKQIDvaikvlkqgtekaDTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPLHK 424
Cdd:cd14042  25 TGYYKGNLVAIKKVNKKRID-------------LTREVLKELKHMRDLQHDNLTRFIGACvDPPNICILTEYCPKGSLQD 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 425 FLvgKREEIPVSN--VAELLHQVSMGMKYLEEKNFV-HRDLAARNVLLVNRHYAKISDFGLSkALGADDSYYTARSAGKW 501
Cdd:cd14042  92 IL--ENEDIKLDWmfRYSLIHDIVKGMHYLHDSEIKsHGNLKSSNCVVDSRFVLKITDFGLH-SFRSGQEPPDDSHAYYA 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 502 PLKWYAPE--CINFRKF--SSRSDVWSYGVTMWEaLSYGQKPYkkmkGPEVMAF----IEQGKRMEC--PP--------E 563
Cdd:cd14042 169 KLLWTAPEllRDPNPPPpgTQKGDVYSFGIILQE-IATRQGPF----YEEGPDLspkeIIKKKVRNGekPPfrpsldelE 243
                       250       260       270
                ....*....|....*....|....*....|.
gi 31455611 564 CPPELYALMSDCWIYKWEDRPDFLTVEQRMR 594
Cdd:cd14042 244 CPDEVLSLMQRCWAEDPEERPDFSTLRNKLK 274
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
344-593 1.90e-11

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 65.46  E-value: 1.90e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYrmrkKQIDVAIKVLKQGT-EKADTEEMMREAQIMHqldNPYIVRLIGVCQ---AEALM---LVMEM 416
Cdd:cd14054   3 IGQGRYGTVWKGSL----DERPVAVKVFPARHrQNFQNEKDIYELPLME---HSNILRFIGADErptADGRMeylLVLEY 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEK---------NFVHRDLAARNVLLVNRHYAKISDFGLSKALg 487
Cdd:cd14054  76 APKGSLCSYL--RENTLDWMSSCRMALSLTRGLAYLHTDlrrgdqykpAIAHRDLNSRNVLVKADGSCVICDFGLAMVL- 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 488 ADDSYYTARS--AGKW------PLKWYAPE----CINFRKFSS---RSDVWSYGVTMWEA------LSYG------QKPY 540
Cdd:cd14054 153 RGSSLVRGRPgaAENAsisevgTLRYMAPEvlegAVNLRDCESalkQVDVYALGLVLWEIamrcsdLYPGesvppyQMPY 232
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 541 KKMKGP----EVMAFIEQGKRMEcpPECPPE----------LYALMSDCWIYKWEDRPDFLTVEQRM 593
Cdd:cd14054 233 EAELGNhptfEDMQLLVSREKAR--PKFPDAwkenslavrsLKETIEDCWDQDAEARLTALCVEERL 297
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
7-101 2.09e-11

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 60.77  E-value: 2.09e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   7 HLPFFYGSISRAEAEEhlKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQlNGTYAIAGGKAHCGPAELCEF 86
Cdd:cd09937   2 LMPWFHGKISREEAER--LLQPPEDGLFLVRESTNYPGDYTLCVSFEGKVEHYRVIYR-NGKLTIDEEEYFENLIQLVEH 78
                        90
                ....*....|....*
gi 31455611  87 YSRDPDGLPCNLRKP 101
Cdd:cd09937  79 YTKDADGLCTRLVKP 93
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
159-254 2.15e-11

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 60.75  E-value: 2.15e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKE-QGTYALSL-----IYGKTVYHYLI-SQDKAGKYCIPEGTkFDT 231
Cdd:cd10363   1 ETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETtKGSYSLSVrdydpQHGDTVKHYKIrTLDNGGFYISPRST-FST 79
                        90       100
                ....*....|....*....|...
gi 31455611 232 LWQLVEYLKLKADGLIYCLKEAC 254
Cdd:cd10363  80 LQELVDHYKKGNDGLCQKLSVPC 102
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
343-531 2.44e-11

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 65.05  E-value: 2.44e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQID---VAIKVLK-QGTEKADTEEMMREAQIMHQLD---NPYIVRLIGVC------QAEA 409
Cdd:cd07862   8 EIGEGAYGKV----FKARDLKNGgrfVALKRVRvQTGEEGMPLSTIREVAVLRHLEtfeHPNVVRLFDVCtvsrtdRETK 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 LMLVMEMAGGGpLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALga 488
Cdd:cd07862  84 LTLVFEHVDQD-LTTYLDKVPEPgVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIY-- 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 489 ddSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWE 531
Cdd:cd07862 161 --SFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAE 201
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
9-104 2.81e-11

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 60.69  E-value: 2.81e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHF---PIERQLNGTYAIAGGKAH-CGPAELC 84
Cdd:cd10413   6 PWFHGRISREESQRLIGQQGLVDGVFLVRESQRNPQGFVLSLCHLQKVKHYlilPSEEEGRLYFSMDDGQTRfTDLLQLV 85
                        90       100
                ....*....|....*....|
gi 31455611  85 EFYSRDPDGLPCNLRKPCNR 104
Cdd:cd10413  86 EFHQLNRGILPCLLRHCCTR 105
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
163-250 2.96e-11

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 60.45  E-value: 2.96e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQTDGKFLLRPRKE-QGTYALSLI-----YGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLV 236
Cdd:cd10365   5 WYFGKITRRESERLLLNAENPRGTFLVRESETtKGAYCLSVSdfdnaKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLV 84
                        90
                ....*....|....
gi 31455611 237 EYLKLKADGLIYCL 250
Cdd:cd10365  85 AYYSKHADGLCHRL 98
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
343-540 3.21e-11

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 64.75  E-value: 3.21e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKadtEEMMREAQIMHQLDNPYIVR-LIGVCQAEALMLVMEMAGGGP 421
Cdd:cd06654  27 KIGQGASGTVYTAMDVATGQEVAIRQMNLQQQPKK---ELIINEILVMRENKNPNIVNyLDSYLVGDELWVVMEYLAGGS 103
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKflVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyytARSAGKW 501
Cdd:cd06654 104 LTD--VVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQS---KRSTMVG 178
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd06654 179 TPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIE-GEPPY 216
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
381-556 3.47e-11

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271011 [Multi-domain]  Cd Length: 255  Bit Score: 64.07  E-value: 3.47e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 381 EEMMREAQIMHQLDNPYIVRL--IGVCQAEALMLVMEMAGGGPLHK-FLVGKREEIPVSNVAELLHQVSMGMKYLEEKNF 457
Cdd:cd14109  41 PFLMREVDIHNSLDHPNIVQMhdAYDDEKLAVTVIDNLASTIELVRdNLLPGKDYYTERQVAVFVRQLLLALKHMHDLGI 120
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 458 VHRDLAARNVLLVNRHYaKISDFGLSKALgaDDSYYTARSAGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQ 537
Cdd:cd14109 121 AHLDLRPEDILLQDDKL-KLADFGQSRRL--LRGKLTTLIYGS-P-EFVSPEIVNSYPVTLATDMWSVGVLTYVLLG-GI 194
                       170
                ....*....|....*....
gi 31455611 538 KPYKKMKGPEVMAFIEQGK 556
Cdd:cd14109 195 SPFLGDNDRETLTNVRSGK 213
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
344-481 4.03e-11

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 60.92  E-value: 4.03e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTE---EMMREAQIMhqldNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:cd13968   1 MGEGASAKVFWAEGECTTIGVAVKIGDDVNNEEGEDLEsemDILRRLKGL----ELNIPKVLVTEdVDGPNILLMELVKG 76
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31455611 420 GPLHKFLVGkrEEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFG 481
Cdd:cd13968  77 GTLIAYTQE--EELDEKDVESIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
356-534 4.39e-11

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 63.96  E-value: 4.39e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 356 VYRMRKKQIDV------AIKVL----KQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA--LMLVMEMaGGGPLH 423
Cdd:cd14001  15 VYLMKRSPRGGssrspwAVKKInskcDKGQRSLYQERLKEEAKILKSLNHPNIVGFRAFTKSEDgsLCLAMEY-GGKSLN 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 424 KFLVGKREE----IPVSNVAELLHQVSMGMKYLE-EKNFVHRDLAARNVLLVNRHYA-KISDFGLSKALGAD---DSYYT 494
Cdd:cd14001  94 DLIEERYEAglgpFPAATILKVALSIARALEYLHnEKKILHGDIKSGNVLIKGDFESvKLCDFGVSLPLTENlevDSDPK 173
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 495 ARSAGKWPlkWYAPECINFRK-FSSRSDVWSYGVTMWEALS 534
Cdd:cd14001 174 AQYVGTEP--WKAKEALEEGGvITDKADIFAYGLVLWEMMT 212
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
344-555 4.50e-11

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 64.24  E-value: 4.50e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLkqgTEKADTeemMREAQIMHQLDN-PYIVRLIGVCQAEA-LMLVMEMAGGGP 421
Cdd:cd14092  14 LGDGSFSVCRKCVHKKTGQEF--AVKIV---SRRLDT---SREVQLLRLCQGhPNIVKLHEVFQDELhTYLVMELLRGGE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA---KISDFGLSKALGADDSYYTarsa 498
Cdd:cd14092  86 LLE-RIRKKKRFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTDEDDDaeiKIVDFGFARLKPENQPLKT---- 160
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 499 gkwP---LKWYAPECIN----FRKFSSRSDVWSYGVTMWEALSyGQKPY----KKMKGPEVMAFIEQG 555
Cdd:cd14092 161 ---PcftLPYAAPEVLKqalsTQGYDESCDLWSLGVILYTMLS-GQVPFqspsRNESAAEIMKRIKSG 224
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
348-534 4.66e-11

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 63.98  E-value: 4.66e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 348 NFGSVRQGVYRMRKK-------QIdVAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAG 418
Cdd:cd07846   5 NLGLVGEGSYGMVMKcrhketgQI-VAIKKFLESEDDKMVKKIaMREIKMLKQLRHENLVNLIEVFrRKKRWYLVFEFVD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 G---GPLHKFLVGKREEIpvsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd07846  84 HtvlDDLEKYPNGLDESR----VRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLAAPGEVYTD 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWplkWYAPE-CINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07846 160 YVATRW---YRAPElLVGDTKYGKAVDVWAVGCLVTEMLT 196
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
343-531 4.89e-11

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 63.88  E-value: 4.89e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGp 421
Cdd:cd07871  12 KLGEGTYATVFKG--RSKLTENLVALKEIRLEHEEGAPCTAIREVSLLKNLKHANIVTLHDIIHTErCLTLVFEYLDSD- 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAgkw 501
Cdd:cd07871  89 LKQYLDNCGNLMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLARAKSVPTKTYSNEVV--- 165
                       170       180       190
                ....*....|....*....|....*....|..
gi 31455611 502 pLKWYAPE--CINFRKFSSRSDVWSYGVTMWE 531
Cdd:cd07871 166 -TLWYRPPdvLLGSTEYSTPIDMWGVGCILYE 196
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
159-255 5.10e-11

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 59.51  E-value: 5.10e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKL-YSGAQTdGKFLLRPRKEQ-GTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLV 236
Cdd:cd10369   1 QAEPWFFGAIKRADAEKQLlYSENQT-GAFLIRESESQkGEFSLSVLDGGVVKHYRIRRLDEGGFFLTRRKTFSTLNEFV 79
                        90
                ....*....|....*....
gi 31455611 237 EYLKLKADGLiyCLKEACP 255
Cdd:cd10369  80 NYYTTTSDGL--CVKLGKP 96
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
344-533 5.35e-11

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 64.13  E-value: 5.35e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAiKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRL--IGVCQAEALMLVMEMAGGGp 421
Cdd:cd07856  18 VGMGAFGLVCSARDQLTGQNVAVK-KIMKPFSTPVLAKRTYRELKLLKHLRHENIISLsdIFISPLEDIYFVTELLGTD- 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVsnVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKalgADDSYYTARSAGKW 501
Cdd:cd07856  96 LHRLLTSRPLEKQF--IQYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLAR---IQDPQMTGYVSTRY 170
                       170       180       190
                ....*....|....*....|....*....|...
gi 31455611 502 plkWYAPEC-INFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd07856 171 ---YRAPEImLTWQKYDVEVDIWSAGCIFAEML 200
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
343-539 5.40e-11

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 63.61  E-value: 5.40e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVrqgvYRMRKKQiDVAIKVLKQGTEKADTEEM----MREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMA 417
Cdd:cd07839   7 KIGEGTYGTV----FKAKNRE-THEIVALKRVRLDDDDEGVpssaLREICLLKELKHKNIVRLYDVLHSDKkLTLVFEYC 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGpLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd07839  82 DQD-LKKYFDSCNGDIDPEIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARAFGIPVRCYSAEV 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 498 AgkwpLKWYAPECINF--RKFSSRSDVWSYGVTMWEaLSYGQKP 539
Cdd:cd07839 161 V----TLWYRPPDVLFgaKLYSTSIDMWSAGCIFAE-LANAGRP 199
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
9-101 5.65e-11

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 59.32  E-value: 5.65e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRaEAEEHLKLAGMaDGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFYS 88
Cdd:cd09935   4 SWYHGPISR-NAAEYLLSSGI-NGSFLVRESESSPGQYSISLRYDGRVYHYRISEDSDGKVYVTQEHRFNTLAELVHHHS 81
                        90
                ....*....|...
gi 31455611  89 RDPDGLPCNLRKP 101
Cdd:cd09935  82 KNADGLITTLRYP 94
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
344-541 5.77e-11

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 64.05  E-value: 5.77e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyrMRKKQIDV-AIKVLKQGT--EKADTEEMMREAQIMH-QLDNPYIVRLIGVCQA-EALMLVMEMAG 418
Cdd:cd05591   3 LGKGSFGKVMLA---ERKGTDEVyAIKVLKKDVilQDDDVDCTMTEKRILAlAAKHPFLTALHSCFQTkDRLFFVMEYVN 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlGADDSYYTARSA 498
Cdd:cd05591  80 GGDL-MFQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKE-GILNGKTTTTFC 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 499 GKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYK 541
Cdd:cd05591 158 GT-P-DYIAPEILQELEYGPSVDWWALGVLMYEMMA-GQPPFE 197
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
343-540 6.04e-11

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 63.97  E-value: 6.04e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKadtEEMMREAQIMHQLDNPYIVR-LIGVCQAEALMLVMEMAGGGP 421
Cdd:cd06656  26 KIGQGASGTVYTAIDIATGQEVAIKQMNLQQQPKK---ELIINEILVMRENKNPNIVNyLDSYLVGDELWVVMEYLAGGS 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKflVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyytARSAGKW 501
Cdd:cd06656 103 LTD--VVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQS---KRSTMVG 177
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd06656 178 TPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY 215
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
162-255 6.49e-11

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 59.38  E-value: 6.49e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 162 PWYHSSLTREEAErKLYSGAQTDGKFLLRPRKE-QGTYALSLIYGKTVYHYLISQDKAGKYCI--PEGTK---FDTLWQL 235
Cdd:cd10343   4 PWYHGNITRSKAE-ELLSKAGKDGSFLVRDSESvSGAYALCVLYQNCVHTYRILPNAEDKLSVqaSEGVPvrfFTTLPEL 82
                        90       100
                ....*....|....*....|
gi 31455611 236 VEYLKLKADGLIYCLKEACP 255
Cdd:cd10343  83 IEFYQKENMGLVTHLLYPVE 102
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
340-540 6.96e-11

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270752 [Multi-domain]  Cd Length: 328  Bit Score: 63.87  E-value: 6.96e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 340 ADIEL----GCGNFGSVRQgvyrMRKKQI-DV-AIKVLKqgteKADT---------EEmmrEAQIMHQLDNPYIVRLIGV 404
Cdd:cd05601   1 KDFEVknviGRGHFGEVQV----VKEKATgDIyAMKVLK----KSETlaqeevsffEE---ERDIMAKANSPWITKLQYA 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 405 CQ-AEALMLVMEMAGGGPLHKfLVGKREEIPVSN-----VAEL---LHQV-SMGmkyleeknFVHRDLAARNVLLVNRHY 474
Cdd:cd05601  70 FQdSENLYLVMEYHPGGDLLS-LLSRYDDIFEESmarfyLAELvlaIHSLhSMG--------YVHRDIKPENILIDRTGH 140
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 475 AKISDFGLSKALGADDsyyTARSagKWPL---KWYAPECINFRKFSSRS------DVWSYGVTMWEALsYGQKPY 540
Cdd:cd05601 141 IKLADFGSAAKLSSDK---TVTS--KMPVgtpDYIAPEVLTSMNGGSKGtygvecDWWSLGIVAYEML-YGKTPF 209
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
344-540 7.79e-11

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 63.53  E-value: 7.79e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGG 420
Cdd:cd05571   3 LGKGTFGKVILC--REKATGELYAIKILKKEViiAKDEVAHTLTENRVLQNTRHPFLTSLKYSFQtNDRLCFVMEYVNGG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKR---EEIPVSNVAELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKalgADDSY-YTAR 496
Cdd:cd05571  81 ELFFHLSRERvfsEDRTRFYGAEIV----LALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFGLCK---EEISYgATTK 153
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 497 SAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05571 154 TFCGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPF 195
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
343-619 8.36e-11

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 65.14  E-value: 8.36e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   343 ELGCGNFGSVRQgVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA---LMLVMEMAGG 419
Cdd:PTZ00266   20 KIGNGRFGEVFL-VKHKRTQEFFCWKAISYRGLKEREKSQLVIEVNVMRELKHKNIVRYIDRFLNKAnqkLYILMEFCDA 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   420 GPLHKF------LVGKREEIPVSNVA-ELLHQVSMGMKYLEEKN---FVHRDLAARNVLLVN--RHY------------- 474
Cdd:PTZ00266   99 GDLSRNiqkcykMFGKIEEHAIVDITrQLLHALAYCHNLKDGPNgerVLHRDLKPQNIFLSTgiRHIgkitaqannlngr 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   475 --AKISDFGLSKALGADDsyyTARSAGKWPLKWyAPECI--NFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKgpEVMA 550
Cdd:PTZ00266  179 piAKIGDFGLSKNIGIES---MAHSCVGTPYYW-SPELLlhETKSYDDKSDMWALGCIIYE-LCSGKTPFHKAN--NFSQ 251
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31455611   551 FIEQGKRmecPPECP-----PELYALMSDCWIYKWEDRPDFLtveqrmRACYYSLASKVeGPPGSTQKAEAACA 619
Cdd:PTZ00266  252 LISELKR---GPDLPikgksKELNILIKNLLNLSAKERPSAL------QCLGYQIIKNV-GPPVGAAGGGAGVA 315
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
344-566 8.51e-11

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270893 [Multi-domain]  Cd Length: 268  Bit Score: 62.91  E-value: 8.51e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQimhqLDNPYIVRLIG-VCQAEALMLVMEMAGGGPL 422
Cdd:cd13991  14 IGRGSFGEV----HRMEDKQTGFQCAVKKVRLEVFRAEELMACAG----LTSPRVVPLYGaVREGPWVNIFMDLKEGGSL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN--RHyAKISDFGLSKALGADDSYYTARSAGK 500
Cdd:cd13991  86 GQ-LIKEQGCLPEDRALHYLGQALEGLEYLHSRKILHGDVKADNVLLSSdgSD-AFLCDFGHAECLDPDGLGKSLFTGDY 163
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 501 WP--LKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKK-MKGPEVMAFIEQGKRM-ECPPECPP 566
Cdd:cd13991 164 IPgtETHMAPEVVLGKPCDAKVDVWSSCCMMLHMLN-GCHPWTQyYSGPLCLKIANEPPPLrEIPPSCAP 232
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
344-548 9.58e-11

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 63.36  E-value: 9.58e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgvYRMRKKQIDVAIKVLKQG--TEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGG 420
Cdd:cd05585   2 IGKGSFGKVMQ--VRKKDTSRIYALKTIRKAhiVSRSEVTHTLAERTVLAQVDCPFIVPLKFSFQSpEKLYLVLAFINGG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PL-HKFLVGKREEIPVSN--VAELLhqvsMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKaLGADDSYYTARS 497
Cdd:cd05585  80 ELfHHLQREGRFDLSRARfyTAELL----CALECLHKFNVIYRDLKPENILLDYTGHIALCDFGLCK-LNMKDDDKTNTF 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 31455611 498 AGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEV 548
Cdd:cd05585 155 CGT-P-EYLAPELLLGHGYTKAVDWWTLGVLLYEMLT-GLPPFYDENTNEM 202
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
9-101 1.30e-10

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 58.36  E-value: 1.30e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFH-----HFPIERQLNGTYAIAGGKAHCGPAEL 83
Cdd:cd09933   4 EWFFGKIKRKDAEKLLLAPGNPRGTFLIRESETTPGAYSLSVRDGDDARgdtvkHYRIRKLDNGGYYITTRATFPTLQEL 83
                        90
                ....*....|....*...
gi 31455611  84 CEFYSRDPDGLPCNLRKP 101
Cdd:cd09933  84 VQHYSKDADGLCCRLTVP 101
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
344-559 1.30e-10

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270759 [Multi-domain]  Cd Length: 288  Bit Score: 62.59  E-value: 1.30e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqGVYRMRKKQIDVAIKVL--KQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd05608   9 LGKGGFGEV--SACQMRATGKLYACKKLnkKRLKKRKGYEGAMVEKRILAKVHSRFIVSLAYAFQTKTdLCLVMTIMNGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEIPVSNVAELLH---QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgADDSYYTARS 497
Cdd:cd05608  87 DLRYHIYNVDEENPGFQEPRACFytaQIISGLEHLHQRRIIYRDLKPENVLLDDDGNVRISDLGLAVEL-KDGQTKTKGY 165
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31455611 498 AGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSygqkpykkMKGPevmaFIEQGKRME 559
Cdd:cd05608 166 AGT-P-GFMAPELLLGEEYDYSVDYFTLGVTLYEMIA--------ARGP----FRARGEKVE 213
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
344-573 1.45e-10

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271017 [Multi-domain]  Cd Length: 248  Bit Score: 61.90  E-value: 1.45e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKqiDVAIKVLKQGTEKadTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14115   1 IGRGRFSIVKKCLHKATRK--DVAVKFVSKKMKK--KEQAAHEAALLQHLQHPQYITLHDTYESPTsYILVLELMDDGRL 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGkREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL-VNRHYAKISDFGLSKALGADDSYYTARSAGKw 501
Cdd:cd14115  77 LDYLMN-HDELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIdLRIPVPRVKLIDLEDAVQISGHRHVHHLLGN- 154
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 502 PlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPykkmkgpevmaFIEQGKRMECPPEC------PPELYALMS 573
Cdd:cd14115 155 P-EFAAPEVIQGTPVSLATDIWSIGVLTYVMLS-GVSP-----------FLDESKEETCINVCrvdfsfPDEYFGDVS 219
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
158-254 1.48e-10

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 58.38  E-value: 1.48e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 158 HERMPWYHSSLTREEAERKLYSGAQTDGKFLLR--PRKEQGtYALSLIYGKTVYHYLI---SQDKAGKYCIPEG-TKFDT 231
Cdd:cd10413   2 HRTQPWFHGRISREESQRLIGQQGLVDGVFLVResQRNPQG-FVLSLCHLQKVKHYLIlpsEEEGRLYFSMDDGqTRFTD 80
                        90       100
                ....*....|....*....|....
gi 31455611 232 LWQLVEYLKLKAdGLIYC-LKEAC 254
Cdd:cd10413  81 LLQLVEFHQLNR-GILPClLRHCC 103
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
342-540 1.66e-10

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 62.07  E-value: 1.66e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGVYRMRKKQidVAIKvlKQGTEKADTEEMM-REAQIMHQLDNPYIVR-----LIGvcqaEALMLVME 415
Cdd:cd06648  13 VKIGEGSTGIVCIATDKSTGRQ--VAVK--KMDLRKQQRRELLfNEVVIMRDYQHPNIVEmyssyLVG----DELWVVME 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKFLVGKREEIPvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTA 495
Cdd:cd06648  85 FLEGGALTDIVTHTRMNEE--QIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKEVP--RR 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 31455611 496 RSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd06648 161 KSLVGTPY-WMAPEVISRLPYGTEVDIWSLGIMVIEMVD-GEPPY 203
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
344-531 1.77e-10

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 61.98  E-value: 1.77e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVLKQgTEKADTEEMMREAQIMHQLDNPYIVRLIG-VCQAEALMLVMEMAGGG 420
Cdd:cd06645  19 IGSGTYGDV----YKARNVNTGelAAIKVIKL-EPGEDFAVVQQEIIMMKDCKHSNIVAYFGsYLRRDKLWICMEFCGGG 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKF--LVGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADdsyYTARSA 498
Cdd:cd06645  94 SLQDIyhVTGPLSE---SQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITAT---IAKRKS 167
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 31455611 499 GKWPLKWYAPECINFRK---FSSRSDVWSYGVTMWE 531
Cdd:cd06645 168 FIGTPYWMAPEVAAVERkggYNQLCDIWAVGITAIE 203
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
163-253 2.10e-10

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 57.99  E-value: 2.10e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQTDGKFLLRPRKE-QGTYALSL-----IYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLV 236
Cdd:cd10367   5 WYFGKIGRKDAERQLLSPGNPRGAFLIRESETtKGAYSLSIrdwdqNRGDHVKHYKIRKLDTGGYYITTRAQFDTVQELV 84
                        90
                ....*....|....*..
gi 31455611 237 EYLKLKADGLIYCLKEA 253
Cdd:cd10367  85 QHYMEVNDGLCYLLTAP 101
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
343-534 2.22e-10

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 61.47  E-value: 2.22e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQgtekADTEEMMREAQIMHQLDNPYIVRLIG-VCQAEALMLVMEMAGGGP 421
Cdd:cd14110  10 EINRGRFSVVRQCEEKRSGQMLAAKIIPYKP----EDKQLVLREYQVLRRLSHPRIAQLHSaYLSPRHLVLIEELCSGPE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSagKW 501
Cdd:cd14110  86 LLYNL-AERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKVLMTDKK--GD 162
                       170       180       190
                ....*....|....*....|....*....|...
gi 31455611 502 PLKWYAPECINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd14110 163 YVETMAPELLEGQGAGPQTDIWAIGVTAFIMLS 195
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
344-540 2.30e-10

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 62.07  E-value: 2.30e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd05612   9 IGTGTFGRVHLVRDRISEHYYALKVMAIPEVIRLKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRfLYMLMEYVPGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREeipVSNVAELLH--QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAgk 500
Cdd:cd05612  89 FSYLRNSGR---FSNSTGLFYasEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKL--RDRTWTLCGT-- 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 31455611 501 wPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05612 162 -P-EYLAPEVIQSKGHNKAVDWWALGILIYEMLV-GYPPF 198
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
344-540 2.38e-10

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 62.29  E-value: 2.38e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgvyrMRKKQID---VAIKVLKQGT--EKADTEEMMREAQIM-HQLDNPYIVRLIGVCQ-AEALMLVMEM 416
Cdd:cd05604   4 IGKGSFGKVL-----LAKRKRDgkyYAVKVLQKKVilNRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQtTDKLYFVLDF 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHkFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlGADDSYYTAR 496
Cdd:cd05604  79 VNGGELF-FHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCKE-GISNSDTTTT 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 497 SAGKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05604 157 FCGT-P-EYLAPEVIRKQPYDNTVDWWCLGSVLYEML-YGLPPF 197
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
344-544 2.43e-10

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270756 [Multi-domain]  Cd Length: 285  Bit Score: 61.60  E-value: 2.43e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVL-KQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGG 420
Cdd:cd05605   8 LGKGGFGEVCACQVRATGKM--YACKKLeKKRIKKRKGEAMaLNEKQILEKVNSRFVVSLAYAYETkDALCLVLTIMNGG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLhKFLV------GKREEIPVSNVAEllhqVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDsyyT 494
Cdd:cd05605  86 DL-KFHIynmgnpGFEEERAVFYAAE----ITCGLEHLHSERIVYRDLKPENILLDDHGHVRISDLGLAVEIPEGE---T 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 31455611 495 AR----SAGkwplkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMK 544
Cdd:cd05605 158 IRgrvgTVG-----YMAPEVVKNERYTFSPDWWGLGCLIYEMIE-GQAPFRARK 205
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
344-584 2.68e-10

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 61.56  E-value: 2.68e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLKqgTEKADTEEMMREAQIM-----HQLDNPY---IVRLIGVCQAEALMLVME 415
Cdd:cd06636  24 VGNGTYGQVYKG--RHVKTGQLAAIKVMD--VTEDEEEEIKLEINMLkkyshHRNIATYygaFIKKSPPGHDDQLWLVME 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKFLVG-KREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgadDSYYT 494
Cdd:cd06636 100 FCGAGSVTDLVKNtKGNALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQL---DRTVG 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 495 ARSAGKWPLKWYAPECINFRK-----FSSRSDVWSYGVTMWEaLSYGQKPYKKMKGPEVMAFIeqgkrmecPPECPPEL- 568
Cdd:cd06636 177 RRNTFIGTPYWMAPEVIACDEnpdatYDYRSDIWSLGITAIE-MAEGAPPLCDMHPMRALFLI--------PRNPPPKLk 247
                       250       260
                ....*....|....*....|....
gi 31455611 569 --------YALMSDCWIYKWEDRP 584
Cdd:cd06636 248 skkwskkfIDFIEGCLVKNYLSRP 271
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
386-583 2.69e-10

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 61.58  E-value: 2.69e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 386 EAQIMHQLDNPYIVRLIGVC---QAEALMLVMEMAGGGPLHKFLvgKREEIPVSNVA-ELLHQVSMGMKYLEEKNFVHRD 461
Cdd:cd06653  54 EIQLLKNLRHDRIVQYYGCLrdpEEKKLSIFVEYMPGGSVKDQL--KAYGALTENVTrRYTRQILQGVSYLHSNMIVHRD 131
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 462 LAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSygQKPyk 541
Cdd:cd06653 132 IKGANILRDSAGNVKLGDFGASKRIQTICMSGTGIKSVTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLT--EKP-- 207
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 542 KMKGPEVMAFIEQGKRMECPPECPPELYALMSDCW--IYKWEDR 583
Cdd:cd06653 208 PWAEYEAMAAIFKIATQPTKPQLPDGVSDACRDFLrqIFVEEKR 251
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
10-104 2.78e-10

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb10 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198278  Cd Length: 108  Bit Score: 57.72  E-value: 2.78e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHF---PIERQLNGTYAIAGGKAHCGP-AELCE 85
Cdd:cd10415   7 WFHGRISREESHRIIKQQGLVDGLFLLRDSQSNPKAFVLTLCHHQKIKNFqilPCEDDGQTFFSLDDGNTKFSDlIQLVD 86
                        90
                ....*....|....*....
gi 31455611  86 FYSRDPDGLPCNLRKPCNR 104
Cdd:cd10415  87 FYQLNKGVLPCKLKHHCIR 105
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
343-544 2.79e-10

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143374 [Multi-domain]  Cd Length: 303  Bit Score: 62.02  E-value: 2.79e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMagggp 421
Cdd:cd07869  12 KLGEGSYATVYKGKSKVNGKL--VALKVIRLQEEEGTPFTAIREASLLKGLKHANIVLLHDIIHTkETLTLVFEY----- 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIP----VSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd07869  85 VHTDLCQYMDKHPgglhPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLARAKSVPSHTYSNEV 164
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 498 AgkwpLKWYAPE--CINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMK 544
Cdd:cd07869 165 V----TLWYRPPdvLLGSTEYSTCLDMWGVGCIFVEMIQ-GVAAFPGMK 208
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
10-94 2.85e-10

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 57.05  E-value: 2.85e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFYSR 89
Cdd:cd10348   2 WLHGALDRNEAVEILKQKADADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDDKWFYIDDGPYFESLEHLIEHYTQ 81

                ....*
gi 31455611  90 DPDGL 94
Cdd:cd10348  82 FADGL 86
STKc_Sid2p_like cd05600
Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the ...
342-534 2.97e-10

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270751 [Multi-domain]  Cd Length: 386  Bit Score: 62.36  E-value: 2.97e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVrqgvYRMRKKQID--VAIKVLKQGT-EKAD-TEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEM 416
Cdd:cd05600  17 TQVGQGGYGSV----FLARKKDTGeiCALKIMKKKVlFKLNeVNHVLTERDILTTTNSPWLVKLLYAFQdPENVYLAMEY 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLVGK---REEIPVSNVAELLHQVSMgmkyLEEKNFVHRDLAARNVLLVNRHYAKISDFGLS---------- 483
Cdd:cd05600  93 VPGGDFRTLLNNSgilSEEHARFYIAEMFAAISS----LHQLGYIHRDLKPENFLIDSSGHIKLTDFGLAsgtlspkkie 168
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 484 --------------------------KALGADDSYYtARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd05600 169 smkirleevkntafleltakerrniyRAMRKEDQNY-ANSVVGSP-DYMAPEVLRGEGYDLTVDYWSLGCILFECLV 243
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
347-484 3.05e-10

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270761 [Multi-domain]  Cd Length: 349  Bit Score: 62.20  E-value: 3.05e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 347 GNFGSVRQGVYRMRKKQIdvAIKVLKQG--TEKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGGPLH 423
Cdd:cd05610  15 GAFGKVYLGRKKNNSKLY--AVKVVKKAdmINKNMVHQVQAERDALALSKSPFIVHLYYSLQsANNVYLVMEYLIGGDVK 92
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31455611 424 KFL--VGK-REEIPVSNVAEllhqVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK 484
Cdd:cd05610  93 SLLhiYGYfDEEMAVKYISE----VALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSK 152
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
343-594 3.12e-10

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 61.20  E-value: 3.12e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKaDTEEMMREAQIMHQL-DNPYIVRLIG------VCQAEALMLvME 415
Cdd:cd13985   7 QLGEGGFSYVYLAHDVNTGRR--YALKRMYFNDEE-QLRVAIKEIEIMKRLcGHPNIVQYYDsailssEGRKEVLLL-ME 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHkfLVGKREEIPVSnVAELLH---QVSMGMKYLEEKN--FVHRDLAARNVLLVNRHYAKISDFGlsKALGADD 490
Cdd:cd13985  83 YCPGSLVD--ILEKSPPSPLS-EEEVLRifyQICQAVGHLHSQSppIIHRDIKIENILFSNTGRFKLCDFG--SATTEHY 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYYTARSAG--------KWPLKWYAPECIN-FRKF--SSRSDVWSYGVTMWEaLSYGQKPYkkmKGPEVMAFIEQGKRME 559
Cdd:cd13985 158 PLERAEEVNiieeeiqkNTTPMYRAPEMIDlYSKKpiGEKADIWALGCLLYK-LCFFKLPF---DESSKLAIVAGKYSIP 233
                       250       260       270
                ....*....|....*....|....*....|....*
gi 31455611 560 CPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMR 594
Cdd:cd13985 234 EQPRYSPELHDLIRHMLTPDPAERPDIFQVINIIT 268
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
356-549 3.31e-10

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270987 [Multi-domain]  Cd Length: 294  Bit Score: 61.38  E-value: 3.31e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 356 VYRMRKK--QIDVAIKVLKQgteKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPLHKFLVGK--- 429
Cdd:cd14085  19 VYRCRQKgtQKPYAVKKLKK---TVDKKIVRTEIGVLLRLSHPNIIKLKEIFETPTeISLVLELVTGGELFDRIVEKgyy 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 430 REEIPVSNVAELLHQVSmgmkYLEEKNFVHRDLAARNVLlvnrhYA--------KISDFGLSKALgadDSYYTARSAGKW 501
Cdd:cd14085  96 SERDAADAVKQILEAVA----YLHENGIVHRDLKPENLL-----YAtpapdaplKIADFGLSKIV---DQQVTMKTVCGT 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 502 PlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVM 549
Cdd:cd14085 164 P-GYCAPEILRGCAYGPEVDMWSVGVITYILLC-GFEPFYDERGDQYM 209
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
344-573 3.49e-10

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 61.99  E-value: 3.49e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrQGVYRMRKKQiDVAIKVLKQGTEK-ADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-------LMLVME 415
Cdd:cd07878  23 VGSGAYGSV-CSAYDTRLRQ-KVAVKKLSRPFQSlIHARRTYRELRLLKHMKHENVIGLLDVFTPATsienfneVYLVTN 100
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGpLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlgADDSyYTA 495
Cdd:cd07878 101 LMGAD-LNNIV--KCQKLSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQ--ADDE-MTG 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWplkWYAPEC-INFRKFSSRSDVWSYGVTMWEALsygqkpykkmKGPEVMA---FIEQGKR-MECPPECPPELYA 570
Cdd:cd07878 175 YVATRW---YRAPEImLNWMHYNQTVDIWSVGCIMAELL----------KGKALFPgndYIDQLKRiMEVVGTPSPEVLK 241

                ...
gi 31455611 571 LMS 573
Cdd:cd07878 242 KIS 244
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
341-531 3.60e-10

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 61.56  E-value: 3.60e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 341 DIELGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEKadtEEM----MREAQIMHQLDNPYIVRLIGVC-----QAEALM 411
Cdd:cd07866  13 LGKLGEGTFGEVYKARQIKTGRV--VALKKILMHNEK---DGFpitaLREIKILKKLKHPNVVPLIDMAverpdKSKRKR 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 412 LVMEMAGggP-----LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKal 486
Cdd:cd07866  88 GSVYMVT--PymdhdLSGLLENPSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLAR-- 163
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 gaddSYYTARSAGKWPL-------------KWY-APECI-NFRKFSSRSDVWSYGVTMWE 531
Cdd:cd07866 164 ----PYDGPPPNPKGGGgggtrkytnlvvtRWYrPPELLlGERRYTTAVDIWGIGCVFAE 219
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
412-573 4.08e-10

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 62.58  E-value: 4.08e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  412 LVMEMAGGGPLhkflvgkREEIP---------VSNVAELLH-QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFG 481
Cdd:PTZ00283 116 LVLDYANAGDL-------RQEIKsraktnrtfREHEAGLLFiQVLLAVHHVHSKHMIHRDIKSANILLCSNGLVKLGDFG 188
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  482 LSKALGADDSYYTARSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSYgQKPYKKMKGPEVMAFIEQGKRMECP 561
Cdd:PTZ00283 189 FSKMYAATVSDDVGRTFCGTPY-YVAPEIWRRKPYSKKADMFSLGVLLYELLTL-KRPFDGENMEEVMHKTLAGRYDPLP 266
                        170
                 ....*....|..
gi 31455611  562 PECPPELYALMS 573
Cdd:PTZ00283 267 PSISPEMQEIVT 278
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
159-251 4.20e-10

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 57.26  E-value: 4.20e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGAQtDGKFLLRPRKEQGTYALSLI------YGKTVYHYLISQDKAGKYCIPEGTKFDTL 232
Cdd:cd10398   4 EIYEWYHKNITRNQAERLLRQESK-EGAFIVRDSRHLGSYTISVFtrarrsTEASIKHYQIKKNDSGQWYVAERHLFQSI 82
                        90
                ....*....|....*....
gi 31455611 233 WQLVEYLKLKADGLIYCLK 251
Cdd:cd10398  83 PELIQYHQHNAAGLMSRLR 101
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
344-552 4.26e-10

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 61.06  E-value: 4.26e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGPL 422
Cdd:cd14169  11 LGEGAFSEVV--LAQERGSQRLVALKCIPKKALRGKEAMVENEIAVLRRINHENIVSLEDIYESPThLYLAMELVTGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLlvnrhYAK--------ISDFGLSKaLGADDSYYT 494
Cdd:cd14169  89 FDRII-ERGSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLL-----YATpfedskimISDFGLSK-IEAQGMLST 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 495 ARSAGkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFI 552
Cdd:cd14169 162 ACGTP----GYVAPELLEQKPYGKAVDVWAIGVISYILLC-GYPPFYDENDSELFNQI 214
STKc_SPEG_rpt1 cd14108
Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle ...
343-540 4.27e-10

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271010 [Multi-domain]  Cd Length: 255  Bit Score: 60.69  E-value: 4.27e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmrKKQIDVAIKVLKQGTEKADTEemMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGP 421
Cdd:cd14108   9 EIGRGAFSYLRRVKEK--SSDLSFAAKFIPVRAKKKTSA--RRELALLAELDHKSIVRFHDAFEKRrVVIIVTELCHEEL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKflVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNR--HYAKISDFGLSKALGADDSYYTARSAG 499
Cdd:cd14108  85 LER--ITKRPTVCESEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLMADQktDQVRICDFGNAQELTPNEPQYCKYGTP 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 500 kwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14108 163 ----EFVAPEIVNQSPVSKVTDIWPVGVIAYLCLT-GISPF 198
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
342-576 4.84e-10

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 60.75  E-value: 4.84e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGVYRMRKkqidVAIKVLkqgtEKADTEEMMREAQIMHQ--LDNPYIVRLI--------GVCQaeaLM 411
Cdd:cd14056   1 KTIGKGRYGEVWLGKYRGEK----VAVKIF----SSRDEDSWFRETEIYQTvmLRHENILGFIaadikstgSWTQ---LW 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 412 LVMEMAGGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNF--------VHRDLAARNVLLVNRHYAKISDFGLs 483
Cdd:cd14056  70 LITEYHEHGSLYDYL--QRNTLDTEEALRLAYSAASGLAHLHTEIVgtqgkpaiAHRDLKSKNILVKRDGTCCIADLGL- 146
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 484 kALgaddSYYTARSAGKWPL------KWY-APEC----INFRKFSS--RSDVWSYGVTMWEALSYG---------QKPYK 541
Cdd:cd14056 147 -AV----RYDSDTNTIDIPPnprvgtKRYmAPEVlddsINPKSFESfkMADIYSFGLVLWEIARRCeiggiaeeyQLPYF 221
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 31455611 542 KMKGP----EVMAFI--EQGKRMECPP-----ECPPELYALMSDCW 576
Cdd:cd14056 222 GMVPSdpsfEEMRKVvcVEKLRPPIPNrwksdPVLRSMVKLMQECW 267
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
344-533 4.87e-10

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 61.53  E-value: 4.87e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  344 LGCGNFGSVRQGVYRmRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:PTZ00426  38 LGTGSFGRVILATYK-NEDFPPVAIKRFEKSKiiKQKQVDHVFSERKILNYINHPFCVNLYGSFKDESyLYLVLEFVIGG 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  421 PLHKFLvGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAGk 500
Cdd:PTZ00426 117 EFFTFL-RRNKRFPNDVGCFYAAQIVLIFEYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKVV--DTRTYTLCGTP- 192
                        170       180       190
                 ....*....|....*....|....*....|...
gi 31455611  501 wplKWYAPECINFRKFSSRSDVWSYGVTMWEAL 533
Cdd:PTZ00426 193 ---EYIAPEILLNVGHGKAADWWTLGIFIYEIL 222
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
343-556 5.15e-10

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 60.80  E-value: 5.15e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMrkKQIDVAIKVLKQgTEKADTEE---MMREAQimhqldNPYIVRLIGVC-QAEALMLVME-MA 417
Cdd:cd14177  11 DIGVGSYSVCKRCIHRA--TNMEFAVKIIDK-SKRDPSEEieiLMRYGQ------HPNIITLKDVYdDGRYVYLVTElMK 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLV----NRHYAKISDFGLSKALGADDSY- 492
Cdd:cd14177  82 GGELLDRIL--RQKFFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYMddsaNADSIRICDFGFAKQLRGENGLl 159
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611 493 ----YTArsagkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKkmKGP-----EVMAFIEQGK 556
Cdd:cd14177 160 ltpcYTA--------NFVAPEVLMRQGYDAACDIWSLGVLLYTMLA-GYTPFA--NGPndtpeEILLRIGSGK 221
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
344-540 5.40e-10

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270753 [Multi-domain]  Cd Length: 339  Bit Score: 61.19  E-value: 5.40e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIM-HQLDNPYIVRLIGVCQ-AEALMLVMEMAGG 419
Cdd:cd05602  15 IGKGSFGKVL--LARHKSDEKFYAVKVLQKKAilKKKEEKHIMSERNVLlKNVKHPFLVGLHFSFQtTDKLYFVLDYING 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLvgKREEIPVSNVAELLH-QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlGADDSYYTARSA 498
Cdd:cd05602  93 GELFYHL--QRERCFLEPRARFYAaEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKE-NIEPNGTTSTFC 169
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 31455611 499 GKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05602 170 GT-P-EYLAPEVLHKQPYDRTVDWWCLGAVLYEML-YGLPPF 208
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
343-534 5.56e-10

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 61.16  E-value: 5.56e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGvyRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGGp 421
Cdd:cd07872  13 KLGEGTYATVFKG--RSKLTENLVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIVHTDkSLTLVFEYLDKD- 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAgkw 501
Cdd:cd07872  90 LKQYMDDCGNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSVPTKTYSNEVV--- 166
                       170       180       190
                ....*....|....*....|....*....|....*
gi 31455611 502 pLKWYAPE--CINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07872 167 -TLWYRPPdvLLGSSEYSTQIDMWGVGCIFFEMAS 200
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
356-534 6.08e-10

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270825 [Multi-domain]  Cd Length: 282  Bit Score: 60.36  E-value: 6.08e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 356 VYRM--RKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQL-DNPYIVRLIGVC---QAEALMLVMEMAGGGpLHKFLVGK 429
Cdd:cd07831  15 VLKAqsRKTGKYYAIKCMKKHFKSLEQVNNLREIQALRRLsPHPNILRLIEVLfdrKTGRLALVFELMDMN-LYELIKGR 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 430 REEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHyAKISDFGlskalgaddsyyTARS-AGKWPL----- 503
Cdd:cd07831  94 KRPLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKDDI-LKLADFG------------SCRGiYSKPPYteyis 160
                       170       180       190
                ....*....|....*....|....*....|....
gi 31455611 504 -KWY-APECI-NFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07831 161 tRWYrAPECLlTDGYYGPKMDIWAVGCVFFEILS 194
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
344-556 6.10e-10

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 61.04  E-value: 6.10e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgvYRMRKKQIDVAIKVLKQGTEkADTEemmREAQIMHQLD-NPYIVRLIGVCQAE-ALMLVMEMAGGGP 421
Cdd:cd14180  14 LGEGSFSVCRK--CRHRQSGQEYAVKIISRRME-ANTQ---REVAALRLCQsHPNIVALHEVLHDQyHTYLVMELLRGGE 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH---YAKISDFGLSKalgaddsyytARSA 498
Cdd:cd14180  88 LLD-RIKKKARFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYADESdgaVLKVIDFGFAR----------LRPQ 156
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31455611 499 GKWP-------LKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKG-------PEVMAFIEQGK 556
Cdd:cd14180 157 GSRPlqtpcftLQYAAPELFSNQGYDESCDLWSLGVILYTMLS-GQVPFQSKRGkmfhnhaADIMHKIKEGD 227
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
344-568 7.80e-10

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 60.06  E-value: 7.80e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgVYRMRKKQiDVAIKVLKQGTEKADTEEMMR----EAQIMHQLDNPYIVRLIGVC---QAEALMLVMEM 416
Cdd:cd06652  10 LGQGAFGRVYL-CYDADTGR-ELAVKQVQFDPESPETSKEVNalecEIQLLKNLLHERIVQYYGCLrdpQERTLSIFMEY 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLvgKREEIPVSNVA-ELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd06652  88 MPGGSIKDQL--KSYGALTENVTrKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTICLSGTG 165
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611 496 RSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYgQKPYKKMkgpEVMAFIEQGKRMECPPECPPEL 568
Cdd:cd06652 166 MKSVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTE-KPPWAEF---EAMAAIFKIATQPTNPQLPAHV 234
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
162-238 7.96e-10

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 55.73  E-value: 7.96e-10
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 162 PWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQ-GTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEY 238
Cdd:cd10360   1 PWYFSGISRTQAQQLLLSPPNEPGAFLIRPSESSlGGYSLSVRAQAKVCHYRICMAPSGSLYLQKGRLFPGLEELLAY 78
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
344-540 8.05e-10

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271070 [Multi-domain]  Cd Length: 301  Bit Score: 60.45  E-value: 8.05e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQIdvAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGPL 422
Cdd:cd14168  18 LGTGAFSEVVLAEERATGKLF--AVKCIPKKALKGKESSIENEIAVLRKIKHENIVALEDIYESpNHLYLVMQLVSGGEL 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 423 HKFLVGKREEIPvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAK---ISDFGLSKALGADDSYYTARSAG 499
Cdd:cd14168  96 FDRIVEKGFYTE-KDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLYFSQDEESkimISDFGLSKMEGKGDVMSTACGTP 174
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 500 kwplKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd14168 175 ----GYVAPEVLAQKPYSKAVDCWSIGVIAYILLC-GYPPF 210
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
8-64 8.08e-10

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 55.46  E-value: 8.08e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611   8 LPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQ 64
Cdd:cd10347   1 LRWYHGKISREVAEALLLREGGRDGLFLVRESTSAPGDYVLSLLAQGEVLHYQIRRH 57
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
344-542 9.69e-10

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 59.67  E-value: 9.69e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVyRMRKKQIdVAIKVLKQ--GTEKADTE----EMMREAQIMHQL-DNPYIVRLIGVCQ-AEALMLVME 415
Cdd:cd13993   8 IGEGAYGVVYLAV-DLRTGRK-YAIKCLYKsgPNSKDGNDfqklPQLREIDLHRRVsRHPNIITLHDVFEtEVAIYIVLE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLH------KFLVGKREEIpvSNVAEllhQVSMGMKYLEEKNFVHRDLAARNVLLVNRHY-AKISDFGLSkalgA 488
Cdd:cd13993  86 YCPNGDLFeaitenRIYVGKTELI--KNVFL---QLIDAVKHCHSLGIYHRDIKPENILLSQDEGtVKLCDFGLA----T 156
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 489 DDSYYTARSAGKwpLKWYAPECINFRK-----FSSRS-DVWSYGVTMWEALSyGQKPYKK 542
Cdd:cd13993 157 TEKISMDFGVGS--EFYMAPECFDEVGrslkgYPCAAgDIWSLGIILLNLTF-GRNPWKI 213
STKc_NDR2 cd05627
Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze ...
344-565 1.10e-09

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270776 [Multi-domain]  Cd Length: 366  Bit Score: 60.46  E-value: 1.10e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgvyrMRKKQID--VAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAG 418
Cdd:cd05627  10 IGRGAFGEVRL----VQKKDTGhiYAMKILRKADmlEKEQVAHIRAERDILVEADGAWVVKMFYSFQdKRNLYLIMEFLP 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALG----------- 487
Cdd:cd05627  86 GGDMMTLLM-KKDTLSEEATQFYIAETVLAIDAIHQLGFIHRDIKPDNLLLDAKGHVKLSDFGLCTGLKkahrtefyrnl 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 488 -----ADDSYY---TARSAGKWPLK-------------WYAPECINFRKFSSRSDVWSYGVTMWEAL--------SYGQK 538
Cdd:cd05627 165 thnppSDFSFQnmnSKRKAETWKKNrrqlaystvgtpdYIAPEVFMQTGYNKLCDWWSLGVIMYEMLigyppfcsETPQE 244
                       250       260
                ....*....|....*....|....*...
gi 31455611 539 PYKK-MKGPEVMAFieqgkrmecPPECP 565
Cdd:cd05627 245 TYRKvMNWKETLVF---------PPEVP 263
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
343-591 1.14e-09

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 59.59  E-value: 1.14e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGvyRMRKKQIDVAIKvlkqgteKADTEEMM---------REAQIMHQLDNPYIVR-LIGVCQAEALML 412
Cdd:cd08224   7 KIGKGQFSVVYRA--RCLLDGRLVALK-------KVQIFEMMdakarqdclKEIDLLQQLNHPNIIKyLASFIENNELNI 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 413 VMEMAGGGPLHKFLVGKREE---IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgad 489
Cdd:cd08224  78 VLELADAGDLSRLIKHFKKQkrlIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFF--- 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 490 dSYYTARSAGKWPLKWY-APECINFRKFSSRSDVWSYGVTMWE--ALsygQKPYK--KMKGPEVMAFIEQGKRMECPPEC 564
Cdd:cd08224 155 -SSKTTAAHSLVGTPYYmSPERIREQGYDFKSDIWSLGCLLYEmaAL---QSPFYgeKMNLYSLCKKIEKCEYPPLPADL 230
                       250       260
                ....*....|....*....|....*...
gi 31455611 565 -PPELYALMSDCWIYKWEDRPDFLTVEQ 591
Cdd:cd08224 231 ySQELRDLVAACIQPDPEKRPDISYVLD 258
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
344-540 1.14e-09

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 60.48  E-value: 1.14e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGG 420
Cdd:cd05593  23 LGKGTFGKVI--LVREKASGKYYAMKILKKEViiAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTkDRLCFVMEYVNGG 100
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLhkFLVGKREEIPVSNVAELL-HQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlGADDSyYTARSAG 499
Cdd:cd05593 101 EL--FFHLSRERVFSEDRTRFYgAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKE-GITDA-ATMKTFC 176
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 500 KWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05593 177 GTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPF 215
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
343-540 1.18e-09

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 59.32  E-value: 1.18e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmrKKQIDVAIKVLKQGTEKADTeeMMR---------EAQIMHQLD---NPYIVRLIGVCQ-AEA 409
Cdd:cd14004   7 EMGEGAYGQVNLAIYK--SKGKEVVIKFIFKERILVDT--WVRdrklgtvplEIHILDTLNkrsHPNIVKLLDFFEdDEF 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 LMLVMEMAGGGpLHKF-LVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGlSKALGA 488
Cdd:cd14004  83 YYLVMEKHGSG-MDLFdFIERKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFG-SAAYIK 160
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 31455611 489 DDSYYTARSAgkwpLKWYAPECINFRKFSSRS-DVWSYGVTMWeALSYGQKPY 540
Cdd:cd14004 161 SGPFDTFVGT----IDYAAPEVLRGNPYGGKEqDIWALGVLLY-TLVFKENPF 208
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
344-558 1.27e-09

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271074 [Multi-domain]  Cd Length: 267  Bit Score: 59.23  E-value: 1.27e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgVYRMRKKQiDVAIKVLkqgtekADTEEMMREAQIMHQLDN-PYIVRLIGVCQ-----AEALMLVMEMA 417
Cdd:cd14172  12 LGLGVNGKVLE-CFHRRTGQ-KCALKLL------YDSPKARREVEHHWRASGgPHIVHILDVYEnmhhgKRCLLIIMECM 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH---YAKISDFGLSKalgaDDSYY 493
Cdd:cd14172  84 EGGELFSRIQERGDQaFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYTSKEkdaVLKLTDFGFAK----ETTVQ 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 494 TARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRM 558
Cdd:cd14172 160 NALQTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLC-GFPPFYSNTGQAISPGMKRRIRM 223
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
163-255 1.31e-09

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 55.80  E-value: 1.31e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQTDGKFLLRPRK-EQGTYALSL----IYGKTVYHYLI-SQDKAGKYCIPEGTkFDTLWQLV 236
Cdd:cd10371   5 WFFRTISRKDAERQLLAPMNKAGSFLIRESEsNKGAFSLSVkdvtTQGEVVKHYKIrSLDNGGYYISPRIT-FPTLQALV 83
                        90
                ....*....|....*....
gi 31455611 237 EYLKLKADGLiyCLKEACP 255
Cdd:cd10371  84 QHYSKKGDGL--CQKLTLP 100
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
349-537 1.36e-09

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 59.62  E-value: 1.36e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 349 FGSVRQGVY----RMRKKQID--VAIKVLKQGTEKADTEEM-MREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMaggg 420
Cdd:cd07848   6 LGVVGEGAYgvvlKCRHKETKeiVAIKKFKDSEENEEVKETtLRELKMLRTLKQENIVELKEAFRRRGkLYLVFEY---- 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 pLHKFLVGKREEIPV----SNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALG-ADDSYYTA 495
Cdd:cd07848  82 -VEKNMLELLEEMPNgvppEKVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSeGSNANYTE 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 31455611 496 RSAGKWplkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQ 537
Cdd:cd07848 161 YVATRW---YRSPELLLGAPYGKAVDMWSVGCILGE-LSDGQ 198
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
356-531 1.45e-09

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270829 [Multi-domain]  Cd Length: 283  Bit Score: 59.23  E-value: 1.45e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 356 VYRMRKKQID--VAIKVLKQGTEkadtEE-----MMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGGpLHKFLV 427
Cdd:cd07835  15 VYKARDKLTGeiVALKKIRLETE----DEgvpstAIREISLLKELNHPNIVRLLDVVHSENkLYLVFEFLDLD-LKKYMD 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 428 GKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNvLLVNRHYA-KISDFGLSKALGADDSYYTARSAGKWplkW 505
Cdd:cd07835  90 SSPLTgLDPPLIKSYLYQLLQGIAFCHSHRVLHRDLKPQN-LLIDTEGAlKLADFGLARAFGVPVRTYTHEVVTLW---Y 165
                       170       180
                ....*....|....*....|....*..
gi 31455611 506 YAPEC-INFRKFSSRSDVWSYGVTMWE 531
Cdd:cd07835 166 RAPEIlLGSKHYSTPVDIWSVGCIFAE 192
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
342-568 1.45e-09

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 59.61  E-value: 1.45e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKadtEEMMREAQIMHQLDNPYIVR-----LIGvcqaEALMLVMEM 416
Cdd:cd06659  27 VKIGEGSTGVVCIAREKHSGRQVAVKMMDLRKQQRR---ELLFNEVVIMRDYQHPNVVEmyksyLVG----EELWVLMEY 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGPLHKFLVGKR-EEIPVSNVAELLHQVSmgmKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTA 495
Cdd:cd06659 100 LQGGALTDIVSQTRlNEEQIATVCEAVLQAL---AYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQISKDVP--KR 174
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611 496 RSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMafieqgKRMECPPecPPEL 568
Cdd:cd06659 175 KSLVGTPY-WMAPEVISRCPYGTEVDIWSLGIMVIEMVD-GEPPYFSDSPVQAM------KRLRDSP--PPKL 237
STKc_NDR1 cd05628
Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze ...
344-565 1.46e-09

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270777 [Multi-domain]  Cd Length: 376  Bit Score: 60.05  E-value: 1.46e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgvyrMRKKQID--VAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAG 418
Cdd:cd05628   9 IGRGAFGEVRL----VQKKDTGhvYAMKILRKADmlEKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLnLYLIMEFLP 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGL---------------- 482
Cdd:cd05628  85 GGDMMTLLM-KKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLLDSKGHVKLSDFGLctglkkahrtefyrnl 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 483 SKALGADDSYY---TARSAGKWPLK-------------WYAPECINFRKFSSRSDVWSYGVTMWEAL--------SYGQK 538
Cdd:cd05628 164 NHSLPSDFTFQnmnSKRKAETWKRNrrqlafstvgtpdYIAPEVFMQTGYNKLCDWWSLGVIMYEMLigyppfcsETPQE 243
                       250       260
                ....*....|....*....|....*...
gi 31455611 539 PYKK-MKGPEVMAFieqgkrmecPPECP 565
Cdd:cd05628 244 TYKKvMNWKETLIF---------PPEVP 262
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
159-246 1.54e-09

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 55.26  E-value: 1.54e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQ-GTYALSL-----IYGKTVYHYLISQDKAGKYCIPEGTKFDTL 232
Cdd:cd10362   1 EPEPWFFKNLSRNDAERQLLAPGNTHGSFLIRESETTaGSFSLSVrdfdqNQGEVVKHYKIRNLDNGGFYISPRITFPGL 80
                        90
                ....*....|....
gi 31455611 233 WQLVEYLKLKADGL 246
Cdd:cd10362  81 HELVRHYTNASDGL 94
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
441-539 1.55e-09

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 59.69  E-value: 1.55e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 441 LLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKWplkWYAPECI-NFRKFSSR 519
Cdd:cd07858 113 FLYQLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLARTTSEKGDFMTEYVVTRW---YRAPELLlNCSEYTTA 189
                        90       100
                ....*....|....*....|
gi 31455611 520 SDVWSYGVTMWEALsyGQKP 539
Cdd:cd07858 190 IDVWSVGCIFAELL--GRKP 207
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
159-251 1.64e-09

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 55.48  E-value: 1.64e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGAQtDGKFLLRPRKEQGTYALSLiYGK-----TVYHYLISQDKAGKYCIPEGTKFDTLW 233
Cdd:cd09934   4 EKYEWYVGDMSRQRAESLLKQEDK-EGCFVVRNSSTKGLYTVSL-FTKvpgspHVKHYHIKQNARSEFYLAEKHCFETIP 81
                        90
                ....*....|....*...
gi 31455611 234 QLVEYLKLKADGLIYCLK 251
Cdd:cd09934  82 ELINYHQHNSGGLATRLK 99
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
9-104 1.68e-09

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 55.71  E-value: 1.68e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHF---PIERQLNGTYAIAGGKAH-CGPAELC 84
Cdd:cd10414   6 PWFHHKISRDEAQRLIIQQGLVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFqiiPVEDDGELFHTLDDGHTRfTDLIQLV 85
                        90       100
                ....*....|....*....|
gi 31455611  85 EFYSRDPDGLPCNLRKPCNR 104
Cdd:cd10414  86 EFYQLNKGVLPCKLKHYCAR 105
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
344-531 1.75e-09

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 58.89  E-value: 1.75e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVLKqgTEKADTEEMMREAQIM-HQLDNPYIVRLIG--VCQaEALMLVMEMAG 418
Cdd:cd06646  17 VGSGTYGDV----YKARNLHTGelAAVKIIK--LEPGDDFSLIQQEIFMvKECKHCNIVAYFGsyLSR-EKLWICMEYCG 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKF--LVGKREEIpvsNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADdsyYTAR 496
Cdd:cd06646  90 GGSLQDIyhVTGPLSEL---QIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKITAT---IAKR 163
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 31455611 497 SAGKWPLKWYAPECINFRK---FSSRSDVWSYGVTMWE 531
Cdd:cd06646 164 KSFIGTPYWMAPEVAAVEKnggYNQLCDIWAVGITAIE 201
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
344-573 1.83e-09

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 59.66  E-value: 1.83e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGG 420
Cdd:cd05594  33 LGKGTFGKVI--LVKEKATGRYYAMKILKKEVivAKDEVAHTLTENRVLQNSRHPFLTALKYSFQThDRLCFVMEYANGG 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLhkFLVGKREEIPVSNVAELL-HQVSMGMKYLE-EKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTARSA 498
Cdd:cd05594 111 EL--FFHLSRERVFSEDRARFYgAEIVSALDYLHsEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGA--TMKTF 186
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 499 GKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQgKRMECPPECPPELYALMS 573
Cdd:cd05594 187 CGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHEKLFELILM-EEIRFPRTLSPEAKSLLS 258
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
343-596 1.84e-09

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 59.27  E-value: 1.84e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMrkKQIDVAIKVLK--QGTEKADTEEMMREAQIMHQLDNPYIVRL-IGVCQAEALMLVMEMAGG 419
Cdd:cd08229  31 KIGRGQFSEVYRATCLL--DGVPVALKKVQifDLMDAKARADCIKEIDLLKQLNHPNVIKYyASFIEDNELNIVLELADA 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFL---VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTAR 496
Cdd:cd08229 109 GDLSRMIkhfKKQKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTT--AAH 186
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 497 SAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEaLSYGQKPY--KKMKGPEVMAFIEQGKRMECPPE-CPPELYALMS 573
Cdd:cd08229 187 SLVGTPY-YMSPERIHENGYNFKSDIWSLGCLLYE-MAALQSPFygDKMNLYSLCKKIEQCDYPPLPSDhYSEELRQLVN 264
                       250       260
                ....*....|....*....|....*.
gi 31455611 574 DCWIYKWEDRPDF---LTVEQRMRAC 596
Cdd:cd08229 265 MCINPDPEKRPDItyvYDVAKRMHAR 290
STKc_TTBK cd14017
Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the ...
343-586 2.37e-09

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270919 [Multi-domain]  Cd Length: 263  Bit Score: 58.42  E-value: 2.37e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQgVYRMRKKQiDVAIKVLKQGTEKaDTEEMmrEAQIMHQLDN-PYIVRLIGVCQAEA-LMLVMEmaggg 420
Cdd:cd14017   7 KIGGGGFGEIYK-VRDVVDGE-EVAMKVESKSQPK-QVLKM--EVAVLKKLQGkPHFCRLIGCGRTERyNYIVMT----- 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 plhkfLVGK----------REEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL----VNRHYAKISDFGLSKAL 486
Cdd:cd14017  77 -----LLGPnlaelrrsqpRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIgrgpSDERTVYILDFGLARQY 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 487 GADDSYYTARSAGKWPLK---WYAP-ECINFRKFSSRSDVWSYGVTMWEaLSYGQKPYKKMKGP-EVMAFIEQGKRMECP 561
Cdd:cd14017 152 TNKDGEVERPPRNAAGFRgtvRYASvNAHRNKEQGRRDDLWSWFYMLIE-FVTGQLPWRKLKDKeEVGKMKEKIDHEELL 230
                       250       260
                ....*....|....*....|....*
gi 31455611 562 PECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd14017 231 KGLPKEFFQILKHIRSLSYFDTPDY 255
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
366-591 2.74e-09

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 58.33  E-value: 2.74e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 366 VAIKVLKQGTEKADtEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGGGPLHKFLVGkrEEIPV--SNVAELL 442
Cdd:cd14045  33 VAIKKIAKKSFTLS-KRIRKEVKQVRELDHPNLCKFIGGCiEVPNVAIITEYCPKGSLNDVLLN--EDIPLnwGFRFSFA 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 443 HQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLsKALGADDSYYTARSAGKWPLKWY-APE--CINFRKFSSR 519
Cdd:cd14045 110 TDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGL-TTYRKEDGSENASGYQQRLMQVYlPPEnhSNTDTEPTQA 188
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611 520 SDVWSYGVTMWEALSYGQkPYKKMKGPEVMAF------IEQGKRME-CPpeCPPELYALMSDCWIYKWEDRPDFLTVEQ 591
Cdd:cd14045 189 TDVYSYAIILLEIATRND-PVPEDDYSLDEAWcpplpeLISGKTENsCP--CPADYVELIRRCRKNNPAQRPTFEQIKK 264
STKc_MAPKAPK2 cd14170
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
335-558 3.96e-09

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271072 [Multi-domain]  Cd Length: 303  Bit Score: 58.51  E-value: 3.96e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 335 DNLLIADIELGCGNFGSVRQGVYRmrKKQIDVAIKVLKqgtekaDTEEMMREAQIMHQLDN-PYIVRLIGVCQ-----AE 408
Cdd:cd14170   1 DDYKVTSQVLGLGINGKVLQIFNK--RTQEKFALKMLQ------DCPKARREVELHWRASQcPHIVRIVDVYEnlyagRK 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 409 ALMLVMEMAGGGPLHKFLVGKREE-IPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH---YAKISDFGLSK 484
Cdd:cd14170  73 CLLIVMECLDGGELFSRIQDRGDQaFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRpnaILKLTDFGFAK 152
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31455611 485 ALGADDSYYTArsagKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRM 558
Cdd:cd14170 153 ETTSHNSLTTP----CYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLC-GYPPFYSNHGLAISPGMKTRIRM 221
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
159-253 4.07e-09

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 54.22  E-value: 4.07e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKE-QGTYALSL-----IYGKTVYHYLI-SQDKAGKYCIPEGTkFDT 231
Cdd:cd10364   1 ETEEWFFKDITRKDAERQLLAPGNSAGAFLIRESETlKGSYSLSVrdydpQHGDVIKHYKIrSLDNGGYYISPRIT-FPC 79
                        90       100
                ....*....|....*....|..
gi 31455611 232 LWQLVEYLKLKADGLIYCLKEA 253
Cdd:cd10364  80 ISDMIKHYQKQSDGLCRRLEKA 101
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
163-255 4.40e-09

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 54.21  E-value: 4.40e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQtDGKFLLRPRKEQ-GTYALS-LIYGKTVYHYLISQdKAGKYCIPEGTKFDTLWQLVEYLK 240
Cdd:cd09931   2 WFHGHLSGKEAEKLLLEKGK-PGSFLVRESQSKpGDFVLSvRTDDDKVTHIMIRC-QGGKYDVGGGEEFDSLTDLVEHYK 79
                        90
                ....*....|....*....
gi 31455611 241 ----LKADGLIYCLKEACP 255
Cdd:cd09931  80 knpmVETSGTVVHLKQPLN 98
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
9-101 5.37e-09

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 53.73  E-value: 5.37e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFYS 88
Cdd:cd10369   4 PWFFGAIKRADAEKQLLYSENQTGAFLIRESESQKGEFSLSVLDGGVVKHYRIRRLDEGGFFLTRRKTFSTLNEFVNYYT 83
                        90
                ....*....|...
gi 31455611  89 RDPDGLPCNLRKP 101
Cdd:cd10369  84 TTSDGLCVKLGKP 96
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
344-534 5.58e-09

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 58.13  E-value: 5.58e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVyrMRKKQIDVAIKVLKQGTEKA-DTEEMMREAQIMHQLDNPYIVRLIGV-CQAEAL------MLVME 415
Cdd:cd07877  25 VGSGAYGSVCAAF--DTKTGLRVAVKKLSRPFQSIiHAKRTYRELRLLKHMKHENVIGLLDVfTPARSLeefndvYLVTH 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGpLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd07877 103 LMGAD-LNNIV--KCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDDEMTGYVA 179
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 496 RsagkwplKWY-APEC-INFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07877 180 T-------RWYrAPEImLNWMHYNQTVDIWSVGCIMAELLT 213
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
343-534 5.77e-09

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 58.04  E-value: 5.77e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRmrKKQIDVAIKVLKQGTE-KADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-------LVM 414
Cdd:cd07880  22 QVGSGAYGTVCSALDR--RTGAKVAIKKLYRPFQsELFAKRAYRELRLLKHMKHENVIGLLDVFTPDLSLdrfhdfyLVM 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGpLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKalgADDSYYT 494
Cdd:cd07880 100 PFMGTD-LGKLM--KHEKLSEDRIQFLVYQMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLAR---QTDSEMT 173
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 31455611 495 ARSAGKWplkWYAPECI-NFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07880 174 GYVVTRW---YRAPEVIlNWMHYTQTVDIWSVGCIMAEMLT 211
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
163-250 6.15e-09

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 53.87  E-value: 6.15e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAERKLYSGAQTDGKFLLRPRKE-QGTYALSL-----IYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLV 236
Cdd:cd10366   5 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETtKGAYSLSIrdwdeVRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 84
                        90
                ....*....|....
gi 31455611 237 EYLKLKADGLIYCL 250
Cdd:cd10366  85 KHYTEHADGLCHKL 98
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
386-539 6.73e-09

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270817 [Multi-domain]  Cd Length: 271  Bit Score: 57.40  E-value: 6.73e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 386 EAQIMHQLDNPYIVRLIGVCQAEA---LMLVMEMAGGGPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDL 462
Cdd:cd06651  59 EIQLLKNLQHERIVQYYGCLRDRAektLTIFMEYMPGGSV-KDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDI 137
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 463 AARNVLLVNRHYAKISDFGLSKALGADDSYYTA-RSAGKWPLkWYAPECINFRKFSSRSDVWSYGVTMWEALSygQKP 539
Cdd:cd06651 138 KGANILRDSAGNVKLGDFGASKRLQTICMSGTGiRSVTGTPY-WMSPEVISGEGYGRKADVWSLGCTVVEMLT--EKP 212
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
344-541 7.54e-09

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 57.53  E-value: 7.54e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQIDVAIKVLKQGTE---KADTEEMMREAQIMHQLDNPYIVRLIGVC-QAEALMLVMEMAGG 419
Cdd:cd14159   1 IGEGGFGCV----YQAVMRNTEYAVKRLKEDSEldwSVVKNSFLTEVEKLSRFRHPNIVDLAGYSaQQGNYCLIYVYLPN 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVSNVAEL--LHQVSMGMKYL--EEKNFVHRDLAARNVLLVNRHYAKISDFGLSK----ALGADDS 491
Cdd:cd14159  77 GSLEDRLHCQVSCPCLSWSQRLhvLLGTARAIQYLhsDSPSLIHGDVKSSNILLDAALNPKLGDFGLARfsrrPKQPGMS 156
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 31455611 492 YYTARSAG-KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYK 541
Cdd:cd14159 157 STLARTQTvRGTLAYLPEEYVKTGTLSVEIDVYSFGVVLLELLT-GRRAME 206
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
11-104 8.29e-09

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 53.44  E-value: 8.29e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  11 FYGSISRAEAEEHLKLAGmADGLFLLRQCLRSLGGYVLS-LVHDVRFHHFPIERQlNGTYAIAGGKAHCGPAELCEFYSR 89
Cdd:cd09931   3 FHGHLSGKEAEKLLLEKG-KPGSFLVRESQSKPGDFVLSvRTDDDKVTHIMIRCQ-GGKYDVGGGEEFDSLTDLVEHYKK 80
                        90
                ....*....|....*....
gi 31455611  90 DP----DGLPCNLRKPCNR 104
Cdd:cd09931  81 NPmvetSGTVVHLKQPLNA 99
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
370-535 8.72e-09

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 57.58  E-value: 8.72e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  370 VLKQGtEKADTeemMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGM 449
Cdd:PHA03209  95 VLKIG-QKGTT---LIEAMLLQNVNHPSVIRMKDTLVSGAITCMVLPHYSSDLYTYLTKRSRPLPIDQALIIEKQILEGL 170
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  450 KYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTArsAGKwpLKWYAPECINFRKFSSRSDVWSYGVTM 529
Cdd:PHA03209 171 RYLHAQRIIHRDVKTENIFINDVDQVCIGDLGAAQFPVVAPAFLGL--AGT--VETNAPEVLARDKYNSKADIWSAGIVL 246

                 ....*.
gi 31455611  530 WEALSY 535
Cdd:PHA03209 247 FEMLAY 252
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
162-240 9.55e-09

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 53.09  E-value: 9.55e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 162 PWYHSSLTREEAERKLYSgaQTDGKFLLRPR-KEQGTYALSLIYGKTVYHYLISQdKAGKYCIPEGTKFDTLWQLVEYLK 240
Cdd:cd10407   6 PWYAGAMERLQAETELIN--RVNSTYLVRHRtKESGEYAISIKYNNEVKHIKILT-RDGFFHIAENRKFKSLMELVEYYK 82
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
343-534 1.00e-08

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 56.44  E-value: 1.00e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKadteEMMREAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGP 421
Cdd:cd14107   9 EIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRA----RAFQERDILARLSHRRLTCLLDQFETrKTLILILELCSSEE 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 L--HKFLVGKREEipvSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN--RHYAKISDFGLSKALGADDSYYTARS 497
Cdd:cd14107  85 LldRLFLKGVVTE---AEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVSptREDIKICDFGFAQEITPSEHQFSKYG 161
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 31455611 498 AGkwplKWYAPECINFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd14107 162 SP----EFVAPEIVHQEPVSAATDIWALGVIAYLSLT 194
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
344-532 1.03e-08

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 56.55  E-value: 1.03e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVLKQ-GTEKADTEEMMREAQIMHQL-DNPYIVRLIGVC-QAEALMLVMEMAG 418
Cdd:cd14050   9 LGEGSFGEV----FKVRSREDGklYAVKRSRSrFRGEKDRKRKLEEVERHEKLgEHPNCVRFIKAWeEKGILYIQTELCD 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGpLHKFLVGKrEEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSA 498
Cdd:cd14050  85 TS-LQQYCEET-HSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGLVVELDKEDIHDAQEGD 162
                       170       180       190
                ....*....|....*....|....*....|....
gi 31455611 499 GkwplKWYAPECINfRKFSSRSDVWSYGVTMWEA 532
Cdd:cd14050 163 P----RYMAPELLQ-GSFTKAADIFSLGITILEL 191
STKc_aPKC cd05588
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the ...
344-540 1.13e-08

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270740 [Multi-domain]  Cd Length: 328  Bit Score: 57.05  E-value: 1.13e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgVYRMRKKQIdVAIKVLKQG--TEKADTEEMMREAQIMHQLDN-PYIVRLIGVCQAEA-LMLVMEMAGG 419
Cdd:cd05588   3 IGRGSYAKVLM-VELKKTKRI-YAMKVIKKElvNDDEDIDWVQTEKHVFETASNhPFLVGLHSCFQTESrLFFVIEFVNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLhKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK-ALGADDSyyTARSA 498
Cdd:cd05588  81 GDL-MFHMQRQRRLPEEHARFYSAEISLALNFLHEKGIIYRDLKLDNVLLDSEGHIKLTDYGMCKeGLRPGDT--TSTFC 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 31455611 499 GKwPlKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd05588 158 GT-P-NYIAPEILRGEDYGFSVDWWALGVLMFEMLA-GRSPF 196
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
344-543 1.17e-08

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 56.65  E-value: 1.17e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGvyRMRKKQIDVAIKVLK-QGTEKADTEE---MMREAQIMHQLDNPY--IVRLIGVCQAEALMLVMEMA 417
Cdd:cd06637  14 VGNGTYGQVYKG--RHVKTGQLAAIKVMDvTGDEEEEIKQeinMLKKYSHHRNIATYYgaFIKKNPPGMDDQLWLVMEFC 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGPLHKFLVG-KREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgadDSYYTAR 496
Cdd:cd06637  92 GAGSVTDLIKNtKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQL---DRTVGRR 168
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 31455611 497 SAGKWPLKWYAPECINFRK-----FSSRSDVWSYGVTMWEaLSYGQKPYKKM 543
Cdd:cd06637 169 NTFIGTPYWMAPEVIACDEnpdatYDFKSDLWSLGITAIE-MAEGAPPLCDM 219
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
344-534 1.23e-08

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 56.61  E-value: 1.23e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKK---QIdVAIKvlkQGTEKADTEEM----MREAQIMHQLDNPYIVRLIGVCQ-AEALMLVME 415
Cdd:cd07847   9 IGEGSYGVV----FKCRNRetgQI-VAIK---KFVESEDDPVIkkiaLREIRMLKQLKHPNLVNLIEVFRrKRKLHLVFE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTA 495
Cdd:cd07847  81 YCDHTVLNE-LEKNPRGVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILTGPGDDYTD 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 31455611 496 RSAGKWplkWYAPECI-NFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07847 160 YVATRW---YRAPELLvGDTQYGPPVDVWAIGCVFAELLT 196
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
367-556 1.41e-08

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 56.09  E-value: 1.41e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 367 AIKVLKQG--TEKADTEEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGGPLhKFLVGKREEIPVSNVAELLH 443
Cdd:cd14189  30 AVKVIPHSrvAKPHQREKIVNEIELHRDLHHKHVVKFSHHFEdAENIYIFLELCSRKSL-AHIWKARHTLLEPEVRYYLK 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 444 QVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTARSAGKWPlKWYAPECINFRKFSSRSDVW 523
Cdd:cd14189 109 QIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPEQ--RKKTICGTP-NYLAPEVLLRQGHGPESDVW 185
                       170       180       190
                ....*....|....*....|....*....|...
gi 31455611 524 SYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK 556
Cdd:cd14189 186 SLGCVMYTLLC-GNPPFETLDLKETYRCIKQVK 217
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
381-541 1.45e-08

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271089 [Multi-domain]  Cd Length: 265  Bit Score: 56.09  E-value: 1.45e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 381 EEMMREAQIMHQLDNPYIVRLIGVCQ-AEALMLVMEMAGGGPL---HKflvgKREEIPVSNVAELLHQVSMGMKYLEEKN 456
Cdd:cd14187  52 EKMSMEIAIHRSLAHQHVVGFHGFFEdNDFVYVVLELCRRRSLlelHK----RRKALTEPEARYYLRQIILGCQYLHRNR 127
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 457 FVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSyyTARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEALsYG 536
Cdd:cd14187 128 VIHRDLKLGNLFLNDDMEVKIGDFGLATKVEYDGE--RKKTLCGTP-NYIAPEVLSKKGHSFEVDIWSIGCIMYTLL-VG 203

                ....*
gi 31455611 537 QKPYK 541
Cdd:cd14187 204 KPPFE 208
STKc_ROCK2 cd05621
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
344-540 1.58e-08

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270771 [Multi-domain]  Cd Length: 379  Bit Score: 56.93  E-value: 1.58e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLK--QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAE-ALMLVMEMAGGG 420
Cdd:cd05621  60 IGRGAFGEVQ--LVRHKASQKVYAMKLLSkfEMIKRSDSAFFWEERDIMAFANSPWVVQLFCAFQDDkYLYMVMEYMPGG 137
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGK 500
Cdd:cd05621 138 DLVNLM--SNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKYGHLKLADFGTCMKMDETGMVHCDTAVGT 215
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 501 wPlKWYAPECINFRK----FSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05621 216 -P-DYISPEVLKSQGgdgyYGRECDWWSVGVFLFEML-VGDTPF 256
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
409-584 1.73e-08

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 55.96  E-value: 1.73e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 409 ALMLVMEMagggpLHKFL-VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKAlg 487
Cdd:cd13975  79 AVLLIMER-----LHRDLyTGIKAGLSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCKP-- 151
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 488 adDSYYTARSAGKwPLKwYAPECINfRKFSSRSDVWSYGVTMWEALSYGQK---PYKKMKGPEVM-AFIEQGKRMECPPE 563
Cdd:cd13975 152 --EAMMSGSIVGT-PIH-MAPELFS-GKYDNSVDVYAFGILFWYLCAGHVKlpeAFEQCASKDHLwNNVRKGVRPERLPV 226
                       170       180
                ....*....|....*....|.
gi 31455611 564 CPPELYALMSDCWIYKWEDRP 584
Cdd:cd13975 227 FDEECWNLMEACWSGDPSQRP 247
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
347-534 2.13e-08

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 55.80  E-value: 2.13e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 347 GNFGSVRQGVYRMRkkqiDVAIKVLKQgTEKAD--TEEMMREAQIMHqldNPYIVRLIGVCQ-----AEALMLVMEMAGG 419
Cdd:cd14053   6 GRFGAVWKAQYLNR----LVAVKIFPL-QEKQSwlTEREIYSLPGMK---HENILQFIGAEKhgeslEAEYWLITEFHER 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 420 GPLHKFLVGKREEIPVsnvaelLHQVSMGM----KYLEE----------KNFVHRDLAARNVLLVNRHYAKISDFGLSKA 485
Cdd:cd14053  78 GSLCDYLKGNVISWNE------LCKIAESMarglAYLHEdipatngghkPSIAHRDFKSKNVLLKSDLTACIADFGLALK 151
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 486 LGADDSyyTARSAGKWPLKWY-APE----CINFRKFS-SRSDVWSYGVTMWEALS 534
Cdd:cd14053 152 FEPGKS--CGDTHGQVGTRRYmAPEvlegAINFTRDAfLRIDMYAMGLVLWELLS 204
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
342-540 2.15e-08

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 55.81  E-value: 2.15e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 342 IELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKadtEEMMREAQIMHQLDNPYIVRLI-GVCQAEALMLVMEMAGGG 420
Cdd:cd06658  28 IKIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRR---ELLFNEVVIMRDYHHENVVDMYnSYLVGDELWVVMEFLEGG 104
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKReeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADdsyYTARSAGK 500
Cdd:cd06658 105 ALTDIVTHTR--MNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKE---VPKRKSLV 179
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 31455611 501 WPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPY 540
Cdd:cd06658 180 GTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMID-GEPPY 218
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
442-534 2.71e-08

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270839 [Multi-domain]  Cd Length: 336  Bit Score: 56.16  E-value: 2.71e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 442 LHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK-ALGADDSY-----YTARsagkwplKWY-APEC-INF 513
Cdd:cd07849 112 LYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLARiADPEHDHTgflteYVAT-------RWYrAPEImLNS 184
                        90       100
                ....*....|....*....|.
gi 31455611 514 RKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07849 185 KGYTKAIDIWSVGCILAEMLS 205
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
344-534 3.21e-08

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 55.94  E-value: 3.21e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTEK-ADTEEMMREAQIMHQLDNPYIVRLIGVC------QAEALMLVMEM 416
Cdd:cd07859   8 IGKGSYGVVCSAIDTHTGEK--VAIKKINDVFEHvSDATRILREIKLLRLLRHPDIVEIKHIMlppsrrEFKDIYVVFEL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AGGGpLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDS---YY 493
Cdd:cd07859  86 MESD-LHQ-VIKANDDLTPEHHQFFLYQLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARVAFNDTPtaiFW 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 494 TARSAGKWplkWYAPECIN--FRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07859 164 TDYVATRW---YRAPELCGsfFSKYTPAIDIWSIGCIFAEVLT 203
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
422-534 4.12e-08

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 55.52  E-value: 4.12e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDS-YYTARSAGK 500
Cdd:cd07853  90 LHKIIV-SPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPDESkHMTQEVVTQ 168
                        90       100       110
                ....*....|....*....|....*....|....*
gi 31455611 501 WplkWYAPECI-NFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07853 169 Y---YRAPEILmGSRHYTSAVDIWSVGCIFAELLG 200
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
442-586 4.24e-08

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 54.63  E-value: 4.24e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 442 LHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALgaDDSYYTARSAGKWPlKWYAPECINFRKFSSRSD 521
Cdd:cd14188 107 LRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARL--EPLEHRRRTICGTP-NYLSPEVLNKQGHGCESD 183
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 31455611 522 VWSYGVTMWEALsYGQKPYKKMKGPEVMAFIEQGkRMECPPECPPELYALMSDCWIYKWEDRPDF 586
Cdd:cd14188 184 IWALGCVMYTML-LGRPPFETTNLKETYRCIREA-RYSLPSSLLAPAKHLIASMLSKNPEDRPSL 246
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
9-104 4.55e-08

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 51.43  E-value: 4.55e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKlaGMADGLFLLRQCLRSLGgYVLSLVHDVRFHHFPIERQLNGTYAIAGGK-AHCGPAELCEFY 87
Cdd:cd10417   8 PWFHGFITRKQTEQLLR--DKALGSFLIRLSDRATG-YILSYRGSDRCRHFVINQLRNRRYLISGDTsSHSTLAELVRHY 84
                        90
                ....*....|....*....
gi 31455611  88 SRDPDGlPCN--LRKPCNR 104
Cdd:cd10417  85 QEVQLE-PFGetLTAACPR 102
STKc_Unc-89_rpt2 cd14112
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated ...
343-541 4.61e-08

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271014 [Multi-domain]  Cd Length: 259  Bit Score: 54.46  E-value: 4.61e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 343 ELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKadtEEMMREAQIMHQLDNPYIVRLIGVCQAEALM-LVMEMAGGGP 421
Cdd:cd14112  10 EIFRGRFSVIVKAVDSTTETDAHCAVKIFEVSDEA---SEAVREFESLRTLQHENVQRLIAAFKPSNFAyLVMEKLQEDV 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 422 LHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRH--YAKISDFGLSKALGaddsyytarSAG 499
Cdd:cd14112  87 FTRFS--SNDYYSEEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMFQSVRswQVKLVDFGRAQKVS---------KLG 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 31455611 500 KWP----LKWYAPECINFR-KFSSRSDVWSYGVTMWEALSyGQKPYK 541
Cdd:cd14112 156 KVPvdgdTDWASPEFHNPEtPITVQSDIWGLGVLTFCLLS-GFHPFT 201
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
164-247 4.95e-08

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 50.83  E-value: 4.95e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 164 YHSSLTREEAErKLYSGAQtDGKFLLR--PRKEqGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVeylkl 241
Cdd:cd10352   9 YHGLISREEAE-QLLSGAS-DGSYLIResSRDD-GYYTLSLRFNGKVKNYKLYYDGKNHYHYVGEKRFDTIHDLV----- 80

                ....*.
gi 31455611 242 kADGLI 247
Cdd:cd10352  81 -ADGLI 85
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
344-533 5.29e-08

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 54.82  E-value: 5.29e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKK---QIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVrliGVCQA----EALMLVMEM 416
Cdd:cd14049  14 LGKGGYGKV----YKVRNKldgQYYAIKKILIKKVTKRDCMKVLREVKVLAGLQHPNIV---GYHTAwmehVQLMLYIQM 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 417 AgggPLHKFL---VGKREEIP--------------VSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLL-VNRHYAKIS 478
Cdd:cd14049  87 Q---LCELSLwdwIVERNKRPceeefksapytpvdVDVTTKILQQLLEGVTYIHSMGIVHRDLKPRNIFLhGSDIHVRIG 163
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31455611 479 DFGLS-KALGADDSYYTARS--------AGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd14049 164 DFGLAcPDILQDGNDSTTMSrlnglthtSGVGTCLYAAPEQLEGSHYDFKSDMYSIGVILLELF 227
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
386-540 5.38e-08

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270990 [Multi-domain]  Cd Length: 265  Bit Score: 54.65  E-value: 5.38e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 386 EAQIMHQLDNPYIVRLIGVCQA-EALMLVMEMAGGGPLHKFLV--GKREEIPVSNVaelLHQVSMGMKYLEEKNFVHRDL 462
Cdd:cd14088  49 EINILKMVKHPNILQLVDVFETrKEYFIFLELATGREVFDWILdqGYYSERDTSNV---IRQVLEAVAYLHSLKIVHRNL 125
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 463 AARNVLLVNR-HYAK--ISDFGLSKalgaddsyyTARSAGKWPL---KWYAPECINFRKFSSRSDVWSYGVTMWEALSyG 536
Cdd:cd14088 126 KLENLVYYNRlKNSKivISDFHLAK---------LENGLIKEPCgtpEYLAPEVVGRQRYGRPVDCWAIGVIMYILLS-G 195

                ....
gi 31455611 537 QKPY 540
Cdd:cd14088 196 NPPF 199
STKc_ROCK1 cd05622
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
326-540 7.50e-08

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270772 [Multi-domain]  Cd Length: 405  Bit Score: 55.01  E-value: 7.50e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 326 KDKKLFLKRDNLLIADIeLGCGNFGSVRqgVYRMRKKQIDVAIKVLK--QGTEKADTEEMMREAQIMHQLDNPYIVRLIG 403
Cdd:cd05622  64 KIRDLRMKAEDYEVVKV-IGRGAFGEVQ--LVRHKSTRKVYAMKLLSkfEMIKRSDSAFFWEERDIMAFANSPWVVQLFY 140
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 404 VCQAEA-LMLVMEMAGGGPLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGL 482
Cdd:cd05622 141 AFQDDRyLYMVMEYMPGGDLVNLM--SNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGT 218
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31455611 483 SKALGADDSYYTARSAGKwPlKWYAPECINFRK----FSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05622 219 CMKMNKEGMVRCDTAVGT-P-DYISPEVLKSQGgdgyYGRECDWWSVGVFLYEML-VGDTPF 277
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
344-484 8.21e-08

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 53.91  E-value: 8.21e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKqID---VAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGV-CQAEALMLVMEMAGG 419
Cdd:cd14046  14 LGKGAFGQV----VKVRNK-LDgryYAIKKIKLRSESKNNSRILREVMLLSRLNHQHVVRYYQAwIERANLYIQMEYCEK 88
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 31455611 420 GPLhkflvgkREEI------PVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK 484
Cdd:cd14046  89 STL-------RDLIdsglfqDTDRLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLAT 152
STKc_DMPK_like cd05597
Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; ...
344-540 9.02e-08

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270748 [Multi-domain]  Cd Length: 331  Bit Score: 54.28  E-value: 9.02e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqGVYRMRKKQIDVAIKVLKQGT--EKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd05597   9 IGRGAFGEV--AVVKLKSTEKVYAMKILNKWEmlKRAETACFREERDVLVNGDRRWITKLHYAFQDENyLYLVMDYYCGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGK 500
Cdd:cd05597  87 DLLTLLSKFEDRLPEEMARFYLAEMVLAIDSIHQLGYVHRDIKPDNVLLDRNGHIRLADFGSCLKLREDGTVQSSVAVGT 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 31455611 501 wP-------LKW-------YAPECinfrkfssrsDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05597 167 -PdyispeiLQAmedgkgrYGPEC----------DWWSLGVCMYEML-YGETPF 208
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
162-243 9.27e-08

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198221  Cd Length: 100  Bit Score: 50.52  E-value: 9.27e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 162 PWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQGT-YALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYLK 240
Cdd:cd10358   3 PWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSAdYVLSVRDTQAVRHYKIWRRAGGRLHLNEAVSFLSLPELVNYHR 82

                ...
gi 31455611 241 LKA 243
Cdd:cd10358  83 AQS 85
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
9-101 9.37e-08

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 50.25  E-value: 9.37e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSlVHDVR------FHHFPIERQLNGTYAIAGGKAHCGPAE 82
Cdd:cd10362   4 PWFFKNLSRNDAERQLLAPGNTHGSFLIRESETTAGSFSLS-VRDFDqnqgevVKHYKIRNLDNGGFYISPRITFPGLHE 82
                        90
                ....*....|....*....
gi 31455611  83 LCEFYSRDPDGLPCNLRKP 101
Cdd:cd10362  83 LVRHYTNASDGLCTRLSRP 101
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
158-254 1.24e-07

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb10 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198278  Cd Length: 108  Bit Score: 50.41  E-value: 1.24e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 158 HERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQ-GTYALSLIYGKTVYHYLI---SQDKAGKYCIPEG-TKFDTL 232
Cdd:cd10415   2 HRTQHWFHGRISREESHRIIKQQGLVDGLFLLRDSQSNpKAFVLTLCHHQKIKNFQIlpcEDDGQTFFSLDDGnTKFSDL 81
                        90       100
                ....*....|....*....|...
gi 31455611 233 WQLVEYLKLKAdGLIYC-LKEAC 254
Cdd:cd10415  82 IQLVDFYQLNK-GVLPCkLKHHC 103
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
344-585 1.33e-07

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 53.38  E-value: 1.33e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKqiDVAIKVLK-QGTEKADTEEM--MREAQImHQLD-------NPYIVRLIGVCQAEALM-L 412
Cdd:cd14182  11 LGRGVSSVVRRCIHKPTRQ--EYAVKIIDiTGGGSFSPEEVqeLREATL-KEIDilrkvsgHPNIIQLKDTYETNTFFfL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 413 VMEMAGGGPLHKFLVgkrEEIPVSN--VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADD 490
Cdd:cd14182  88 VFDLMKKGELFDYLT---EKVTLSEkeTRKIMRALLEVICALHKLNIVHRDLKPENILLDDDMNIKLTDFGFSCQLDPGE 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 491 SYytaRSAGKWPlKWYAPECI------NFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGKRMECPPEc 564
Cdd:cd14182 165 KL---REVCGTP-GYLAPEIIecsmddNHPGYGKEVDMWSTGVIMYTLLA-GSPPFWHRKQMLMLRMIMSGNYQFGSPE- 238
                       250       260
                ....*....|....*....|.
gi 31455611 565 ppelyalmsdcwiykWEDRPD 585
Cdd:cd14182 239 ---------------WDDRSD 244
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
347-533 1.51e-07

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270760 [Multi-domain]  Cd Length: 280  Bit Score: 53.18  E-value: 1.51e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 347 GNFGSV-----RQGVYRMRKKQIDVAIKVLKQGTEKADTEEmmreaQIMHQLDNPYIVRLIgvCQAEA---LMLVMEMAG 418
Cdd:cd05609  11 GAYGAVylvrhRETRQRFAMKKINKQNLILRNQIQQVFVER-----DILTFAENPFVVSMY--CSFETkrhLCMVMEYVE 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 419 GGPLHKfLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSK-------------A 485
Cdd:cd05609  84 GGDCAT-LLKNIGPLPVDMARMYFAETVLALEYLHSYGIVHRDLKPDNLLITSMGHIKLTDFGLSKiglmslttnlyegH 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 31455611 486 LGADDSYYTARSAGKWPlKWYAPECINFRKFSSRSDVWSYGVTMWEAL 533
Cdd:cd05609 163 IEKDTREFLDKQVCGTP-EYIAPEVILRQGYGKPVDWWAMGIILYEFL 209
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
344-534 1.52e-07

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143384 [Multi-domain]  Cd Length: 342  Bit Score: 53.75  E-value: 1.52e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQGTE-KADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-------LMLVMe 415
Cdd:cd07879  23 VGSGAYGSVCSAIDKRTGEK--VAIKKLSRPFQsEIFAKRAYRELTLLKHMQHENVIGLLDVFTSAVsgdefqdFYLVM- 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 magggPLHKFLVGKREEIPVSN--VAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYY 493
Cdd:cd07879 100 -----PYMQTDLQKIMGHPLSEdkVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAVNEDCELKILDFGLARHADAEMTGY 174
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 31455611 494 TARsagkwplKWY-APECI-NFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07879 175 VVT-------RWYrAPEVIlNWMHYNQTVDIWSVGCIMAEMLT 210
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
341-559 1.52e-07

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 53.08  E-value: 1.52e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 341 DIELGCGNFGSVRQGVyrMRKKQIDVAIKVLK-QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-----EALMLVM 414
Cdd:cd14033   6 NIEIGRGSFKTVYRGL--DTETTVEVAWCELQtRKLSKGERQRFSEEVEMLKGLQHPNIVRFYDSWKStvrghKCIILVT 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLVGKReEIPVSNVAELLHQVSMGMKYLEEKN--FVHRDLAARNVLLVN-RHYAKISDFGLSKALGADds 491
Cdd:cd14033  84 ELMTSGTLKTYLKRFR-EMKLKLLQRWSRQILKGLHFLHSRCppILHRDLKCDNIFITGpTGSVKIGDLGLATLKRAS-- 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 492 yyTARSAGKWPlKWYAPECINfRKFSSRSDVWSYGVTMWE-------------------ALSYGQKP--YKKMKGPEVMA 550
Cdd:cd14033 161 --FAKSVIGTP-EFMAPEMYE-EKYDEAVDVYAFGMCILEmatseypysecqnaaqiyrKVTSGIKPdsFYKVKVPELKE 236

                ....*....
gi 31455611 551 FIEQGKRME 559
Cdd:cd14033 237 IIEGCIRTD 245
STKc_ROCK cd05596
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
344-540 1.53e-07

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270747 [Multi-domain]  Cd Length: 352  Bit Score: 53.92  E-value: 1.53e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRqgVYRMRKKQIDVAIKVLK--QGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEA-LMLVMEMAGGG 420
Cdd:cd05596  34 IGRGAFGEVQ--LVRHKSTKKVYAMKLLSkfEMIKRSDSAFFWEERDIMAHANSEWIVQLHYAFQDDKyLYMVMDYMPGG 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 421 PLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGK 500
Cdd:cd05596 112 DLVNLM--SNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLLDASGHLKLADFGTCMKMDKDGLVRSDTAVGT 189
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 31455611 501 wPlKWYAPECI----NFRKFSSRSDVWSYGVTMWEALsYGQKPY 540
Cdd:cd05596 190 -P-DYISPEVLksqgGDGVYGRECDWWSVGVFLYEML-VGDTPF 230
SH2_SAP1a cd10400
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked ...
159-221 1.61e-07

Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX[VI], which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198263  Cd Length: 103  Bit Score: 49.84  E-value: 1.61e-07
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31455611 159 ERMPWYHSSLTREEAERKLYSGAQtDGKFLLRPRKE-QGTYALSLIYGKTVYHYLISQDKAGKY 221
Cdd:cd10400   1 EAVAVYHGKISRETGEKLLLAAGL-DGSYLLRDSESvPGVYCLCVLYKGYVYTYRVSQTETGSW 63
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
344-534 1.71e-07

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 53.63  E-value: 1.71e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQGVYRMRKKQidVAIKVLKQgTEKADTEEMMREAQIMHQLDNPYIVRLIGV---------------CQAE 408
Cdd:cd07854  13 LGCGSNGLVFSAVDSDCDKR--VAVKKIVL-TDPQSVKHALREIKIIRRLDHDNIVKVYEVlgpsgsdltedvgslTELN 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 409 ALMLVMEMAGGGpLHKFLvgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYA-KISDFGLSKALG 487
Cdd:cd07854  90 SVYIVQEYMETD-LANVL--EQGPLSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFINTEDLVlKIGDFGLARIVD 166
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 31455611 488 ADDSYYTARSAGKwPLKWY-APECI-NFRKFSSRSDVWSYGVTMWEALS 534
Cdd:cd07854 167 PHYSHKGYLSEGL-VTKWYrSPRLLlSPNNYTKAIDMWAAGCIFAEMLT 214
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
9-87 1.72e-07

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 48.80  E-value: 1.72e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFY 87
Cdd:cd10360   1 PWYFSGISRTQAQQLLLSPPNEPGAFLIRPSESSLGGYSLSVRAQAKVCHYRICMAPSGSLYLQKGRLFPGLEELLAYY 79
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
163-251 1.94e-07

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 49.32  E-value: 1.94e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 163 WYHSSLTREEAErKLYSGAQTDGKFLLRP-RKEQGTYALSLIYGKTVYHYLIsQDKAGKYCIPEGTKFDTLWQLVEY--- 238
Cdd:cd10340   2 WFHPVISGIEAE-NLLKTRGVDGSFLARPsKSNPGDFTLSVRRGDEVTHIKI-QNTGDYYDLYGGEKFATLSELVQYyme 79
                        90
                ....*....|....*..
gi 31455611 239 ----LKLKaDGLIYCLK 251
Cdd:cd10340  80 qhgqLREK-NGDVIELK 95
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
161-238 1.96e-07

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 48.91  E-value: 1.96e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 161 MPWYHSSLTREEAERKLYSGAQTDGKFLLR-PRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTK-FDTLWQLVEY 238
Cdd:cd10347   1 LRWYHGKISREVAEALLLREGGRDGLFLVReSTSAPGDYVLSLLAQGEVLHYQIRRHGEDAFFSDDGPLiFHGLDTLIEH 80
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
410-556 2.29e-07

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271013 [Multi-domain]  Cd Length: 257  Bit Score: 52.52  E-value: 2.29e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 410 LMLVMEMAGGGPLHKFLVgKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGAD 489
Cdd:cd14111  74 LVLIAEFCSGKELLHSLI-DRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQSFNPL 152
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31455611 490 DSYYTARSAGKwpLKWYAPECINFRKFSSRSDVWSYGVTMWEALSyGQKPYKKMKGPEVMAFIEQGK 556
Cdd:cd14111 153 SLRQLGRRTGT--LEYMAPEMVKGEPVGPPADIWSIGVLTYIMLS-GRSPFEDQDPQETEAKILVAK 216
STKc_HIPK3 cd14229
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; ...
344-540 2.39e-07

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271131 [Multi-domain]  Cd Length: 330  Bit Score: 53.11  E-value: 2.39e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVRQgVYRMRKKQIdVAIKVLKQGTEKADTEEMmrEAQIMHQLDNPY-----IVRLIGVCQAEA-LMLVMEMA 417
Cdd:cd14229   8 LGRGTFGQVVK-CWKRGTNEI-VAVKILKNHPSYARQGQI--EVGILARLSNENadefnFVRAYECFQHRNhTCLVFEML 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 418 GGGpLHKFL-VGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVN----RHYAKISDFG----LSKALGA 488
Cdd:cd14229  84 EQN-LYDFLkQNKFSPLPLKVIRPILQQVATALKKLKSLGLIHADLKPENIMLVDpvrqPYRVKVIDFGsashVSKTVCS 162
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31455611 489 ddSYYTARSagkwplkWYAPECINFRKFSSRSDVWSYGVTMWE----------ALSYGQKPY 540
Cdd:cd14229 163 --TYLQSRY-------YRAPEIILGLPFCEAIDMWSLGCVIAElflgwplypgALEYDQIRY 215
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
341-542 2.41e-07

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 52.42  E-value: 2.41e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 341 DIELGCGNFGSVRQGVYRmrKKQIDVA-IKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQA-----EALMLVM 414
Cdd:cd14031  15 DIELGRGAFKTVYKGLDT--ETWVEVAwCELQDRKLTKAEQQRFKEEAEMLKGLQHPNIVRFYDSWESvlkgkKCIVLVT 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 415 EMAGGGPLHKFLvgKREEIPVSNV-AELLHQVSMGMKYLEEKN--FVHRDLAARNVLLVN-RHYAKISDFGLSKALGADd 490
Cdd:cd14031  93 ELMTSGTLKTYL--KRFKVMKPKVlRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITGpTGSVKIGDLGLATLMRTS- 169
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 31455611 491 syyTARSAGKWPlKWYAPECINfRKFSSRSDVWSYGVTMWEaLSYGQKPYKK 542
Cdd:cd14031 170 ---FAKSVIGTP-EFMAPEMYE-EHYDESVDVYAFGMCMLE-MATSEYPYSE 215
STKc_Sck1_like cd05586
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ...
344-531 2.56e-07

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270738 [Multi-domain]  Cd Length: 330  Bit Score: 52.96  E-value: 2.56e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 344 LGCGNFGSVrqgvYRMRKKQID--VAIKVL--KQGTEKADTEEMMREAQIMHQL---DNPYIVRLIGVCQAEA-LMLVME 415
Cdd:cd05586   1 IGKGTFGQV----YQVRKKDTRriYAMKVLskKVIVAKKEVAHTIGERNILVRTaldESPFIVGLKFSFQTPTdLYLVTD 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 416 MAGGGPL--HKFLVGKREEIPVS-NVAELLhqvsMGMKYLEEKNFVHRDLAARNVLL-VNRHYAkISDFGLSKA-LGADD 490
Cdd:cd05586  77 YMSGGELfwHLQKEGRFSEDRAKfYIAELV----LALEHLHKNDIVYRDLKPENILLdANGHIA-LCDFGLSKAdLTDNK 151
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 31455611 491 SYYTARSAgkwpLKWYAPEC-INFRKFSSRSDVWSYGVTMWE 531
Cdd:cd05586 152 TTNTFCGT----TEYLAPEVlLDEKGYTKMVDFWSLGVLVFE 189
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
9-87 2.80e-07

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 48.29  E-value: 2.80e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKlaGMADGLFLLRQCLRSLGgYVLSLVHDVRFHHFPIERQLNGTYAIAGGK-AHCGPAELCEFY 87
Cdd:cd10349   1 AWFHGFITRREAERLLE--PKPQGCYLVRFSESAVT-FVLSYRSRTCCRHFLLAQLRDGRHVVLGEDsAHARLQDLLLHY 77
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
3-75 1.07e-06

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 47.14  E-value: 1.07e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611   3 DPAAHLPFFYGSISRAEAEEHLKLagmaDGLFLLRQCLRSLGG---YVLSLVHDVRFHHFPIERQLNGTYAIAGGK 75
Cdd:cd10361   1 KDLENEPYYHGLLPREDAEELLKN----DGDFLVRKTEPKGGGkrkLVLSVRWDGKIRHFVINRDDGGKYYIEGKS 72
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
162-238 2.93e-06

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 45.21  E-value: 2.93e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31455611 162 PWYHSSLTREEAERKLYSGAQtdGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIP-EGTKFDTLWQLVEY 238
Cdd:cd10349   1 AWFHGFITRREAERLLEPKPQ--GCYLVRFSESAVTFVLSYRSRTCCRHFLLAQLRDGRHVVLgEDSAHARLQDLLLH 76
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
9-91 5.46e-06

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 45.33  E-value: 5.46e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMaDGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQlnGTYAIAGGKAHCGPAELCEFYS 88
Cdd:cd09932   5 EWFHANLTREQAEEMLMRVPR-DGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQE--GRLFVIGTSQFESLVELVSYYE 81

                ...
gi 31455611  89 RDP 91
Cdd:cd09932  82 KHP 84
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
10-101 7.42e-06

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 44.98  E-value: 7.42e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSL-----VHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELC 84
Cdd:cd10364   5 WFFKDITRKDAERQLLAPGNSAGAFLIRESETLKGSYSLSVrdydpQHGDVIKHYKIRSLDNGGYYISPRITFPCISDMI 84
                        90
                ....*....|....*..
gi 31455611  85 EFYSRDPDGLPCNLRKP 101
Cdd:cd10364  85 KHYQKQSDGLCRRLEKA 101
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
10-102 7.98e-06

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 44.96  E-value: 7.98e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSL-----VHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELC 84
Cdd:cd10363   5 WFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVrdydpQHGDTVKHYKIRTLDNGGFYISPRSTFSTLQELV 84
                        90
                ....*....|....*...
gi 31455611  85 EFYSRDPDGLPCNLRKPC 102
Cdd:cd10363  85 DHYKKGNDGLCQKLSVPC 102
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
9-59 8.92e-06

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 44.28  E-value: 8.92e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 31455611   9 PFFYGS-----ISRAEAEEHLKLAGmaDGLFLLRQCLRSLGGYVLSLVHDVRFHHF 59
Cdd:cd10352   2 PRFYGReyhglISREEAEQLLSGAS--DGSYLIRESSRDDGYYTLSLRFNGKVKNY 55
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
10-101 1.09e-05

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 44.63  E-value: 1.09e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLV--HDVR---FHHFPIERQLNGTYAIAGGKAHCGPAELC 84
Cdd:cd10368   5 WYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRdwDDMKgdhVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....*..
gi 31455611  85 EFYSRDPDGLPCNLRKP 101
Cdd:cd10368  85 QHYSETANGLCKVLIVT 101
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
9-71 1.11e-05

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 44.18  E-value: 1.11e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 31455611   9 PFFYGSISRAEAEEHLKLAGmADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAI 71
Cdd:cd09941   4 PWFHGKISRAEAEEILMNQR-PDGAFLIRESESSPGDFSLSVKFGNDVQHFKVLRDGAGKYFL 65
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
6-89 1.74e-05

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 43.82  E-value: 1.74e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   6 AHLPFFYGSISRAEAEEHLKlaGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCE 85
Cdd:cd09940   3 SEFLWFVGEMERDTAENRLE--NRPDGTYLVRVRPQGETQYALSIKYNGDVKHMKIEQRSDGLYYLSESRHFKSLVELVN 80

                ....
gi 31455611  86 FYSR 89
Cdd:cd09940  81 YYER 84
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
10-101 4.94e-05

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 42.59  E-value: 4.94e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSL-----VHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELC 84
Cdd:cd10367   5 WYFGKIGRKDAERQLLSPGNPRGAFLIRESETTKGAYSLSIrdwdqNRGDHVKHYKIRKLDTGGYYITTRAQFDTVQELV 84
                        90
                ....*....|....*..
gi 31455611  85 EFYSRDPDGLPCNLRKP 101
Cdd:cd10367  85 QHYMEVNDGLCYLLTAP 101
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
11-101 6.61e-05

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 42.39  E-value: 6.61e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  11 FYGSISRAEAEEHLKLAGmADGLFLLRQClRSLGGYVLSL----VHDVRFHHFPIERQLNGTYAIAggKAHCGP--AELC 84
Cdd:cd09934   9 YVGDMSRQRAESLLKQED-KEGCFVVRNS-STKGLYTVSLftkvPGSPHVKHYHIKQNARSEFYLA--EKHCFEtiPELI 84
                        90
                ....*....|....*..
gi 31455611  85 EFYSRDPDGLPCNLRKP 101
Cdd:cd09934  85 NYHQHNSGGLATRLKYP 101
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
10-98 1.14e-04

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 41.58  E-value: 1.14e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSL-----VHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELC 84
Cdd:cd10419   5 WYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIrdwddMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....
gi 31455611  85 EFYSRDPDGLPCNL 98
Cdd:cd10419  85 QHYSEKADGLCFNL 98
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
162-255 1.75e-04

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 41.03  E-value: 1.75e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611 162 PWYHSSLTREEAERKLYSGAQtdGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIP-EGTKFDTLWQLVE-YL 239
Cdd:cd10417   8 PWFHGFITRKQTEQLLRDKAL--GSFLIRLSDRATGYILSYRGSDRCRHFVINQLRNRRYLISgDTSSHSTLAELVRhYQ 85
                        90
                ....*....|....*.
gi 31455611 240 KLKADGLIYCLKEACP 255
Cdd:cd10417  86 EVQLEPFGETLTAACP 101
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
10-101 2.44e-04

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 40.76  E-value: 2.44e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSL-----VHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELC 84
Cdd:cd10418   5 WYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIrdwddMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....*..
gi 31455611  85 EFYSRDPDGLPCNLRKP 101
Cdd:cd10418  85 QHYSERAAGLCCRLVVP 101
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
10-101 2.60e-04

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 40.39  E-value: 2.60e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSlVHDVR-----FHHFPIERQLNGTYAIAGGKAHCGPAELC 84
Cdd:cd10371   5 WFFRTISRKDAERQLLAPMNKAGSFLIRESESNKGAFSLS-VKDVTtqgevVKHYKIRSLDNGGYYISPRITFPTLQALV 83
                        90
                ....*....|....*..
gi 31455611  85 EFYSRDPDGLPCNLRKP 101
Cdd:cd10371  84 QHYSKKGDGLCQKLTLP 100
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
9-104 2.84e-04

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 40.50  E-value: 2.84e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMaDGLFLLRQCLRSLGGYVLSL-----VHDVRFhhFPIERQLNGTYAIAGGKAHCGPA-- 81
Cdd:cd10343   4 PWYHGNITRSKAEELLSKAGK-DGSFLVRDSESVSGAYALCVlyqncVHTYRI--LPNAEDKLSVQASEGVPVRFFTTlp 80
                        90       100
                ....*....|....*....|...
gi 31455611  82 ELCEFYSRDPDGLPCNLRKPCNR 104
Cdd:cd10343  81 ELIEFYQKENMGLVTHLLYPVER 103
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
9-102 6.18e-04

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198221  Cd Length: 100  Bit Score: 39.35  E-value: 6.18e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611   9 PFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFYS 88
Cdd:cd10358   3 PWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKIWRRAGGRLHLNEAVSFLSLPELVNYHR 82
                        90
                ....*....|....
gi 31455611  89 RDPDGLPCNLRKPC 102
Cdd:cd10358  83 AQSLSHGLRLAAPC 96
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
10-94 5.27e-03

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 36.92  E-value: 5.27e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31455611  10 FFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSL-----VHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELC 84
Cdd:cd10366   5 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIrdwdeVRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 84
                        90
                ....*....|
gi 31455611  85 EFYSRDPDGL 94
Cdd:cd10366  85 KHYTEHADGL 94
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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