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Conserved domains on  [gi|15718680|ref|NP_005537|]
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tyrosine-protein kinase ITK/TSK [Homo sapiens]

Protein Classification

tyrosine-protein kinase ITK/TSK( domain architecture ID 10100799)

tyrosine-protein kinase ITK/TSK is a cytoplasmic (or nonreceptor) kinase 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_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
358-613 0e+00

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: 565.73  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd05112   1 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd05112  81 MEHGCLSDYLRTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSSTG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKE 597
Cdd:cd05112 161 TKFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKE 240
                       250
                ....*....|....*.
gi 15718680 598 RPEDRPAFSRLLRQLA 613
Cdd:cd05112 241 RPEDRPSFSLLLRQLA 256
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
7-148 2.18e-70

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 223.64  E-value: 2.18e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   7 LEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRIKCVEIVKSDISipCHYKYPFQVVHDN 86
Cdd:cd01238   1 LEGLLVKRSQGKKRFGPVNYKERWFVLTKSSLSYYEGDGEKRGKEKGSIDLSKVRCVEEVKDEAF--FERKYPFQVVYDD 78
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680  87 YLLYVFAPDRESRQRWVLALKEETRNNNSLVPKYHPNFWMDGKWRCCSQLEKLATGCAQYDP 148
Cdd:cd01238  79 YTLYVFAPSEEDRDEWIAALRKVCRNNSNLHDKYHPGFWTGGKWSCCGQTSKSAPGCQPAFD 140
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
232-340 3.10e-68

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, 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. It is crucial for the function of Tec PH domains and it's lack of presence in Txk 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: 198259  Cd Length: 108  Bit Score: 216.97  E-value: 3.10e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 232 NNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVvSENNPCIKHYHIKETNDNPKRYYVAEKY 311
Cdd:cd10396   1 NNLDQYEWYNKNINRSKAEKLLRDEGKEGGFMVRDSSQPGLYTVSLYTKAG-GEGNPCIRHYHIKETNDSPKKYYLAEKH 79
                        90       100
                ....*....|....*....|....*....
gi 15718680 312 VFDSIPLLINYHQHNGGGLVTRLRYPVCF 340
Cdd:cd10396  80 VFNSIPELIEYHKHNAAGLVTRLRYPVSS 108
SH3_ITK cd11908
Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) ...
174-229 3.47e-38

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212841 [Multi-domain]  Cd Length: 56  Bit Score: 134.76  E-value: 3.47e-38
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 174 TVVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEK 229
Cdd:cd11908   1 TLVIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRVQDKNGHEGYVPSSYLVEK 56
 
Name Accession Description Interval E-value
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
358-613 0e+00

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: 565.73  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd05112   1 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd05112  81 MEHGCLSDYLRTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSSTG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKE 597
Cdd:cd05112 161 TKFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKE 240
                       250
                ....*....|....*.
gi 15718680 598 RPEDRPAFSRLLRQLA 613
Cdd:cd05112 241 RPEDRPSFSLLLRQLA 256
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
363-612 1.57e-130

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: 383.39  E-value: 1.57e-130
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   363 LTFVQEIGSGQFGLVHLGYWL-----NKDKVAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKgegenTKIKVAVKTLKEGADEEerEDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   436 EFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL-DDQYTS 514
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYdDDYYRK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   515 STGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHC 594
Cdd:pfam07714 161 RGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQC 240
                         250
                  ....*....|....*...
gi 15718680   595 WKERPEDRPAFSRLLRQL 612
Cdd:pfam07714 241 WAYDPEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
363-612 6.19e-126

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 371.48  E-value: 6.19e-126
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    363 LTFVQEIGSGQFGLVHLGYWLNKDK-----VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKGKGGkkkveVAVKTLKEDASEQqiEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    436 EFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYRK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    516 TGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCW 595
Cdd:smart00219 161 RGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCW 240
                          250
                   ....*....|....*..
gi 15718680    596 KERPEDRPAFSRLLRQL 612
Cdd:smart00219 241 AEDPEDRPTFSELVEIL 257
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
7-148 2.18e-70

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 223.64  E-value: 2.18e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   7 LEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRIKCVEIVKSDISipCHYKYPFQVVHDN 86
Cdd:cd01238   1 LEGLLVKRSQGKKRFGPVNYKERWFVLTKSSLSYYEGDGEKRGKEKGSIDLSKVRCVEEVKDEAF--FERKYPFQVVYDD 78
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680  87 YLLYVFAPDRESRQRWVLALKEETRNNNSLVPKYHPNFWMDGKWRCCSQLEKLATGCAQYDP 148
Cdd:cd01238  79 YTLYVFAPSEEDRDEWIAALRKVCRNNSNLHDKYHPGFWTGGKWSCCGQTSKSAPGCQPAFD 140
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
232-340 3.10e-68

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, 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. It is crucial for the function of Tec PH domains and it's lack of presence in Txk 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: 198259  Cd Length: 108  Bit Score: 216.97  E-value: 3.10e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 232 NNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVvSENNPCIKHYHIKETNDNPKRYYVAEKY 311
Cdd:cd10396   1 NNLDQYEWYNKNINRSKAEKLLRDEGKEGGFMVRDSSQPGLYTVSLYTKAG-GEGNPCIRHYHIKETNDSPKKYYLAEKH 79
                        90       100
                ....*....|....*....|....*....
gi 15718680 312 VFDSIPLLINYHQHNGGGLVTRLRYPVCF 340
Cdd:cd10396  80 VFNSIPELIEYHKHNAAGLVTRLRYPVSS 108
SH3_ITK cd11908
Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) ...
174-229 3.47e-38

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212841 [Multi-domain]  Cd Length: 56  Bit Score: 134.76  E-value: 3.47e-38
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 174 TVVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEK 229
Cdd:cd11908   1 TLVIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRVQDKNGHEGYVPSSYLVEK 56
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
354-614 6.71e-38

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 146.70  E-value: 6.71e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 354 GKWVIdpseltfVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQ 428
Cdd:COG0515   7 GRYRI-------LRLLGRGGMGVVYLARDLRLGRpVALKVLRPELAADPEARErfrrEARALARLNHPNIVRVYDVGEED 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 429 APICLVFEFMEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL 508
Cdd:COG0515  80 GRPYLVMEYVEGESLADLLR-RRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALG 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG----FRLYKPRLaS 584
Cdd:COG0515 159 GATLTQTGTVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREppppPSELRPDL-P 236
                       250       260       270
                ....*....|....*....|....*....|....
gi 15718680 585 THVYQIMNHCWKERPEDRP----AFSRLLRQLAE 614
Cdd:COG0515 237 PALDAIVLRALAKDPEERYqsaaELAAALRAVLR 270
SH2 pfam00017
SH2 domain;
239-323 1.40e-23

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 94.59  E-value: 1.40e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   239 WYNKSISRDKAEKLLLDTGKEGAFMVRDS-RTAGTYTVSVFTKAVVsennpciKHYHIKETNDnpKRYYVAEKYVFDSIP 317
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESeSTPGGYTLSVRDDGKV-------KHYKIQSTDN--GGYYISGGVKFSSLA 71

                  ....*.
gi 15718680   318 LLINYH 323
Cdd:pfam00017  72 ELVEHY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
237-329 5.40e-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: 87.28  E-value: 5.40e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    237 YEWYNKSISRDKAEKLLLDTGkEGAFMVRDSRT-AGTYTVSVFTKAvvsennpCIKHYHIKETNDNpkRYYVAEKYVFDS 315
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG-DGDFLVRDSESsPGDYVLSVRVKG-------KVKHYRIRRNEDG--KFYLEGGRKFPS 70
                           90
                   ....*....|....
gi 15718680    316 IPLLINYHQHNGGG 329
Cdd:smart00252  71 LVELVEHYQKNSLG 84
BTK smart00107
Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and ...
113-148 5.00e-16

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 128417  Cd Length: 36  Bit Score: 71.64  E-value: 5.00e-16
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 15718680    113 NNSLVPKYHPNFWMDGKWRCCSQLEKLATGCAQYDP 148
Cdd:smart00107   1 NNNLLQKYHPSFWVDGKWLCCQQSEKNAPGCTPYEA 36
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
361-581 2.36e-15

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 77.55  E-value: 2.36e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  361 SELTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGA---MSEEDFI-EEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:PTZ00263  18 SDFEMGETLGTGSFGRVRIAKHKGTGEyYAIKCLKKREilkMKQVQHVaQEKSILMELSHPFIVNMMCSFQDENRVYFLL 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  436 EFMEHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTsS 515
Cdd:PTZ00263  98 EFVVGGELFTHLRKA-GRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVPDRTFT-L 175
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680  516 TGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPYENRSNSEVVEDISTGfRLYKPR 581
Cdd:PTZ00263 176 CGTP---EYLAPEVIQSKGHGKAVDWWTMGVLLYE-FIAGYPPFFDDTPFRIYEKILAG-RLKFPN 236
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
369-560 3.54e-15

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 78.68  E-value: 3.54e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  369 IGSGQFGLVHLGY--WLNKDkVAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLY--GvclEQAPIC-LVFEFME 439
Cdd:NF033483  15 IGRGGMAEVYLAKdtRLDRD-VAVKVLRPDLARDPEFVArfrrEAQSAASLSHPNIVSVYdvG---EDGGIPyIVMEYVD 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  440 hGC-LSDYLRTQRGLFAAETLlGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVlddqyTSST-- 516
Cdd:NF033483  91 -GRtLKDYIREHGPLSPEEAV-EIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARAL-----SSTTmt 163
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 15718680  517 ------GTkfpVKWASPEVfsfSRYSS---KSDVWSFGVLMWEVFSeGKIPYE 560
Cdd:NF033483 164 qtnsvlGT---VHYLSPEQ---ARGGTvdaRSDIYSLGIVLYEMLT-GRPPFD 209
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
177-223 4.59e-15

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 69.54  E-value: 4.59e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 15718680   177 IALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPS 223
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEGLIPS 47
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
172-226 1.05e-14

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 68.72  E-value: 1.05e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 15718680    172 EETVVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYL 226
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYV 55
PH pfam00169
PH domain; PH stands for pleckstrin homology.
5-111 7.51e-14

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 67.97  E-value: 7.51e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680     5 ILLEEQLIKKSQQKRrtspSNFKVRFFVLTKASLAYFEDRHGKK-RTLKGSIELSRIKCVEIVKSDisiPCHYKYPFQVV 83
Cdd:pfam00169   1 VVKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKDDKSGKsKEPKGSISLSGCEVVEVVASD---SPKRKFCFELR 73
                          90       100       110
                  ....*....|....*....|....*....|..
gi 15718680    84 HDNY----LLYVFAPDRESRQRWVLALKEETR 111
Cdd:pfam00169  74 TGERtgkrTYLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
358-613 0e+00

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: 565.73  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd05112   1 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd05112  81 MEHGCLSDYLRTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSSTG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKE 597
Cdd:cd05112 161 TKFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKE 240
                       250
                ....*....|....*.
gi 15718680 598 RPEDRPAFSRLLRQLA 613
Cdd:cd05112 241 RPEDRPSFSLLLRQLA 256
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
358-613 0e+00

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: 522.78  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd05059   1 IDPSELTFLKELGSGQFGVVHLGKWRGKIDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd05059  81 MANGCLLNYLRERRGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYVLDDEYTSSVG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKE 597
Cdd:cd05059 161 TKFPVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHE 240
                       250
                ....*....|....*.
gi 15718680 598 RPEDRPAFSRLLRQLA 613
Cdd:cd05059 241 KPEERPTFKILLSQLT 256
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
358-617 1.03e-147

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: 427.36  E-value: 1.03e-147
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd05114   1 INPSELTFMKELGSGLFGVVRLGKWRAQYKVAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd05114  81 MENGCLLNYLRQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDDQYTSSSG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKE 597
Cdd:cd05114 161 AKFPVKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHE 240
                       250       260
                ....*....|....*....|
gi 15718680 598 RPEDRPAFSRLLRQLAEIAE 617
Cdd:cd05114 241 KPEGRPTFADLLRTITEIAE 260
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
363-612 1.57e-130

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: 383.39  E-value: 1.57e-130
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   363 LTFVQEIGSGQFGLVHLGYWL-----NKDKVAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKgegenTKIKVAVKTLKEGADEEerEDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   436 EFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL-DDQYTS 514
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYdDDYYRK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   515 STGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHC 594
Cdd:pfam07714 161 RGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQC 240
                         250
                  ....*....|....*...
gi 15718680   595 WKERPEDRPAFSRLLRQL 612
Cdd:pfam07714 241 WAYDPEDRPTFSELVEDL 258
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
358-609 4.25e-128

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: 377.30  E-value: 4.25e-128
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd05113   1 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd05113  81 MANGCLLNYLREMRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKE 597
Cdd:cd05113 161 SKFPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTIMYSCWHE 240
                       250
                ....*....|..
gi 15718680 598 RPEDRPAFSRLL 609
Cdd:cd05113 241 KADERPTFKILL 252
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
363-612 6.19e-126

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 371.48  E-value: 6.19e-126
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    363 LTFVQEIGSGQFGLVHLGYWLNKDK-----VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKGKGGkkkveVAVKTLKEDASEQqiEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    436 EFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYRK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    516 TGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCW 595
Cdd:smart00219 161 RGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCW 240
                          250
                   ....*....|....*..
gi 15718680    596 KERPEDRPAFSRLLRQL 612
Cdd:smart00219 241 AEDPEDRPTFSELVEIL 257
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
363-612 1.09e-124

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: 368.41  E-value: 1.09e-124
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    363 LTFVQEIGSGQFGLVHLGYWLNKDK-----VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGKGDgkeveVAVKTLKEDASEQqiEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    436 EFMEHGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPkELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    515 STGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHC 594
Cdd:smart00221 161 VKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQC 240
                          250
                   ....*....|....*...
gi 15718680    595 WKERPEDRPAFSRLLRQL 612
Cdd:smart00221 241 WAEDPEDRPTFSELVEIL 258
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
368-613 2.34e-122

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: 362.63  E-value: 2.34e-122
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYWLNKDK----VAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd00192   2 KLGEGAFGEVYKGKLKGGDGktvdVAVKTLKEDASESErkDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGLFAAE--------TLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ-Y 512
Cdd:cd00192  82 DLLDFLRKSRPVFPSPepstlslkDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDDyY 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMN 592
Cdd:cd00192 162 RKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYELML 241
                       250       260
                ....*....|....*....|.
gi 15718680 593 HCWKERPEDRPAFSRLLRQLA 613
Cdd:cd00192 242 SCWQLDPEDRPTFSELVERLE 262
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
369-608 1.82e-108

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: 326.55  E-value: 1.82e-108
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLR 448
Cdd:cd05034   3 LGAGQFGEVWMGVWNGTTKVAVKTLKPGTMSPEAFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSKGSLLDYLR 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 449 TQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASP 527
Cdd:cd05034  83 TGEGrALRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIEDDEYTAREGAKFPIKWTAP 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 528 EVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSR 607
Cdd:cd05034 163 EAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKKEPEERPTFEY 242

                .
gi 15718680 608 L 608
Cdd:cd05034 243 L 243
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
355-614 2.45e-101

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: 308.95  E-value: 2.45e-101
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd05068   2 QWEIDRKSLKLLRKLGSGQFGEVWEGLWNNTTPVAVKTLKPGTMDPEDFLREAQIMKKLRHPKLIQLYAVCTLEEPIYII 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR-FVLDDQYT 513
Cdd:cd05068  82 TELMKHGSLLEYLQGKGRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARvIKVEDEYE 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNH 593
Cdd:cd05068 162 AREGAKFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYDIMLE 241
                       250       260
                ....*....|....*....|.
gi 15718680 594 CWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05068 242 CWKADPMERPTFETLQWKLED 262
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
356-615 3.37e-99

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: 303.12  E-value: 3.37e-99
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKdKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd05039   1 WAINKKDLKLGELIGKGEFGDVMLGDYRGQ-KVAVKCLKDDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYIVT 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQ-RGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQyts 514
Cdd:cd05039  80 EYMAKGSLVDYLRSRgRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEASSNQ--- 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 sTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHC 594
Cdd:cd05039 157 -DGGKLPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKNC 235
                       250       260
                ....*....|....*....|.
gi 15718680 595 WKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05039 236 WELDPAKRPTFKQLREKLEHI 256
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
367-612 4.05e-93

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: 287.03  E-value: 4.05e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYwLNKDK--VAIKTIREgAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd05041   1 EKIGRGNFGDVYRGV-LKPDNteVAVKTCRE-TLPPDLkrkFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGG 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTK-F 520
Cdd:cd05041  79 SLLTFLRKKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREEEDGEYTVSDGLKqI 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 PVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPE 600
Cdd:cd05041 159 PIKWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPE 238
                       250
                ....*....|..
gi 15718680 601 DRPAFSRLLRQL 612
Cdd:cd05041 239 NRPSFSEIYNEL 250
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
356-606 6.80e-89

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: 276.61  E-value: 6.80e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd05052   1 WEIERTDITMKHKLGGGQYGEVYEGVWKKYNLtVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLR-TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd05052  81 TEFMPYGNLLDYLReCNREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNH 593
Cdd:cd05052 161 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRA 240
                       250
                ....*....|...
gi 15718680 594 CWKERPEDRPAFS 606
Cdd:cd05052 241 CWQWNPSDRPSFA 253
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
355-608 4.54e-87

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: 271.76  E-value: 4.54e-87
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVcLEQAPICLV 434
Cdd:cd05067   1 EWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAIKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAV-VTQEPIYII 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRGL-FAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd05067  80 TEYMENGSLVDFLKTPSGIkLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYT 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNH 593
Cdd:cd05067 160 AREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQLMRL 239
                       250
                ....*....|....*
gi 15718680 594 CWKERPEDRPAFSRL 608
Cdd:cd05067 240 CWKERPEDRPTFEYL 254
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
356-608 2.10e-85

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: 268.06  E-value: 2.10e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd05072   2 WEIPRESIKLVKKLGAGQFGEVWMGYYNNSTKVAVKTLKPGTMSVQAFLEEANLMKTLQHDKLVRLYAVVTKEEPIYIIT 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRGlfaAETLLGMCLD----VCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ 511
Cdd:cd05072  82 EYMAKGSLLDFLKSDEG---GKVLLPKLIDfsaqIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNE 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIM 591
Cdd:cd05072 159 YTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYDIM 238
                       250
                ....*....|....*..
gi 15718680 592 NHCWKERPEDRPAFSRL 608
Cdd:cd05072 239 KTCWKEKAEERPTFDYL 255
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
368-617 2.43e-85

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: 267.29  E-value: 2.43e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYWLNKD----KVAIKTIREGAMS--EEDFIEEAEVMMKLSHPKLVQLYGVCLEQaPICLVFEFMEHG 441
Cdd:cd05060   2 ELGHGNFGSVRKGVYLMKSgkevEVAVKTLKQEHEKagKKEFLREASVMAQLDHPCIVRLIGVCKGE-PLMLVMELAPLG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL--DDQYTSSTGTK 519
Cdd:cd05060  81 PLLKYLK-KRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALGagSDYYRATTAGR 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 520 FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERP 599
Cdd:cd05060 160 WPLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRP 239
                       250
                ....*....|....*...
gi 15718680 600 EDRPAFSRLLRQLAEIAE 617
Cdd:cd05060 240 EDRPTFSELESTFRRDPE 257
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
358-612 1.19e-83

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: 263.08  E-value: 1.19e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDK----VAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPI 431
Cdd:cd05033   1 IDASYVTIEKVIGGGEFGEVCSGSLKLPGKkeidVAIKTLKSGYSDKQrlDFLTEASIMGQFDHPNVIRLEGVVTKSRPV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV--LD 509
Cdd:cd05033  81 MIVTEYMENGSLDKFLRENDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLedSE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGtKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQ 589
Cdd:cd05033 161 ATYTTKGG-KIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSALYQ 239
                       250       260
                ....*....|....*....|...
gi 15718680 590 IMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05033 240 LMLDCWQKDRNERPTFSQIVSTL 262
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
356-615 5.80e-83

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: 261.21  E-value: 5.80e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTI-REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd05148   1 WERPREEFTLERKLGSGYFGEVWEGLWKNRVRVAIKILkSDDLLKQQDFQKEVQALKRLRHKHLISLFAVCSVGEPVYII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd05148  81 TELMEKGSLLAFLRSPEGqVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKEDVYL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTgTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNH 593
Cdd:cd05148 161 SSD-KKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIMLE 239
                       250       260
                ....*....|....*....|..
gi 15718680 594 CWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05148 240 CWAAEPEDRPSFKALREELDNI 261
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
367-608 5.78e-82

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: 257.92  E-value: 5.78e-82
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQaPICLVFEFMEHGCLSDY 446
Cdd:cd14203   1 VKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMSPEAFLEEAQIMKKLRHDKLVQLYAVVSEE-PIYIVTEFMSKGSLLDF 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 447 LRTQRGLFAA-ETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWA 525
Cdd:cd14203  80 LKDGEGKYLKlPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFPIKWT 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 526 SPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAF 605
Cdd:cd14203 160 APEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKDPEERPTF 239

                ...
gi 15718680 606 SRL 608
Cdd:cd14203 240 EYL 242
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
369-613 4.03e-77

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: 245.69  E-value: 4.03e-77
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEED--FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDY 446
Cdd:cd05085   4 LGKGNFGEVYKGTLKDKTPVAVKTCKEDLPQELKikFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGDFLSF 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 447 LRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWAS 526
Cdd:cd05085  84 LRKKKDELKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRQEDDGVYSSSGLKQIPIKWTA 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 527 PEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFS 606
Cdd:cd05085 164 PEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNPENRPKFS 243

                ....*..
gi 15718680 607 RLLRQLA 613
Cdd:cd05085 244 ELQKELA 250
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
356-615 3.03e-76

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: 243.35  E-value: 3.03e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKdKVAIKTIREGAMSEEdFIEEAEVMMKLSHPKLVQLYGVCLEQ-APICLV 434
Cdd:cd05082   1 WALNMKELKLLQTIGKGEFGDVMLGDYRGN-KVAVKCIKNDATAQA-FLAEASVMTQLRHSNLVQLLGVIVEEkGGLYIV 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQ-RGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd05082  79 TEYMAKGSLVDYLRSRgRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQDT 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SstgtKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNH 593
Cdd:cd05082 159 G----KLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDVMKN 234
                       250       260
                ....*....|....*....|..
gi 15718680 594 CWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05082 235 CWHLDAAMRPSFLQLREQLEHI 256
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
361-616 3.49e-76

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: 244.25  E-value: 3.49e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWL-----NKDKVAIKTIRE--GAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQApICL 433
Cdd:cd05057   7 TELEKGKVLGSGAFGTVYKGVWIpegekVKIPVAIKVLREetGPKANEEILDEAYVMASVDHPHLVRLLGICLSSQ-VQL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV-LDDQY 512
Cdd:cd05057  86 ITQLMPLGCLLDYVRNHRDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLdVDEKE 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMN 592
Cdd:cd05057 166 YHAEGGKVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDVYMVLV 245
                       250       260
                ....*....|....*....|....
gi 15718680 593 HCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd05057 246 KCWMIDAESRPTFKELANEFSKMA 269
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
367-612 1.75e-74

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: 238.68  E-value: 1.75e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYwLNKDK--VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd05084   2 ERIGRGNFGEVFSGR-LRADNtpVAVKSCRETLPPDlkAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTK-FP 521
Cdd:cd05084  81 FLTFLRTEGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSREEEDGVYAATGGMKqIP 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 522 VKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPED 601
Cdd:cd05084 161 VKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYDPRK 240
                       250
                ....*....|.
gi 15718680 602 RPAFSRLLRQL 612
Cdd:cd05084 241 RPSFSTVHQDL 251
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
369-614 3.10e-74

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: 238.47  E-value: 3.10e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLN-------KDKVAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd05044   3 LGSGAFGEVFEGTAKDilgdgsgETKVAVKTLRKGATDQEkaEFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILELME 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLR------TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ----VIKVSDFGMTRFVLD 509
Cdd:cd05044  83 GGDLLSYLRaarptaFTPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSKDyrerVVKIGDFGLARDIYK 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGT-KFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05044 163 NDYYRKEGEgLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAGGRLDQPDNCPDDLY 242
                       250       260
                ....*....|....*....|....*.
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05044 243 ELMLRCWSTDPEERPSFARILEQLQN 268
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
369-612 1.23e-73

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: 236.28  E-value: 1.23e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDkVAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 445
Cdd:cd13999   1 IGSGSFGEVYKGKWRGTD-VAIKKLKVEDDNDellKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGGSLYD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV--LDDQYTSSTGTkfpVK 523
Cdd:cd13999  80 LLHKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKnsTTEKMTGVVGT---PR 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 524 WASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVED-ISTGFRLYKPRLASTHVYQIMNHCWKERPEDR 602
Cdd:cd13999 157 WMAPEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIAAAvVQKGLRPPIPPDCPPELSKLIKRCWNEDPEKR 235
                       250
                ....*....|
gi 15718680 603 PAFSRLLRQL 612
Cdd:cd13999 236 PSFSEIVKRL 245
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
356-608 1.79e-73

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: 236.89  E-value: 1.79e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQaPICLVF 435
Cdd:cd05070   4 WEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEE-PIYIVT 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd05070  83 EYMSKGSLLDFLKDGEGrALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEYTA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 STGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHC 594
Cdd:cd05070 163 RQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHC 242
                       250
                ....*....|....
gi 15718680 595 WKERPEDRPAFSRL 608
Cdd:cd05070 243 WKKDPEERPTFEYL 256
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
356-614 2.16e-72

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: 234.16  E-value: 2.16e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLN------KDKVAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLE 427
Cdd:cd05032   1 WELPREKITLIRELGQGSFGMVYEGLAKGvvkgepETRVAIKTVNENASMREriEFLNEASVMKEFNCHHVVRLLGVVST 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 428 QAPICLVFEFMEHGCLSDYLRTQR---------GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKV 498
Cdd:cd05032  81 GQPTLVVMELMAKGDLKSYLRSRRpeaennpglGPPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 499 SDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRL 577
Cdd:cd05032 161 GDFGMTRDIYEtDYYRKGGKGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGHL 240
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 15718680 578 YKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05032 241 DLPENCPDKLLELMRMCWQYNPKMRPTFLEIVSSLKD 277
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
350-605 5.75e-72

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: 233.04  E-value: 5.75e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 350 GLRYGKWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQa 429
Cdd:cd05069   1 GLAKDAWEIPRESLRLDVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE- 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEHGCLSDYLRTQRGLFAA-ETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL 508
Cdd:cd05069  80 PIYIVTEFMGKGSLLDFLKEGDGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIE 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05069 160 DNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCPESLH 239
                       250
                ....*....|....*..
gi 15718680 589 QIMNHCWKERPEDRPAF 605
Cdd:cd05069 240 ELMKLCWKKDPDERPTF 256
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
358-612 7.38e-72

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: 232.66  E-value: 7.38e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYW--LNKDK----VAIKTIRE--GAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQA 429
Cdd:cd05036   3 VPRKNLTLIRALGQGAFGEVYEGTVsgMPGDPsplqVAVKTLPElcSEQDEMDFLMEALIMSKFNHPNIVRCIGVCFQRL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEHGCLSDYLRTQR------GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV---GENQVIKVSD 500
Cdd:cd05036  83 PRFILLELMAGGDLKSFLRENRprpeqpSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLtckGPGRVAKIGD 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 501 FGMTRfvldDQYTSSTGTK-----FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGF 575
Cdd:cd05036 163 FGMAR----DIYRADYYRKggkamLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSGG 238
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 15718680 576 RLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05036 239 RMDPPKNCPGPVYRIMTQCWQHIPEDRPNFSTILERL 275
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
367-614 1.96e-71

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: 231.08  E-value: 1.96e-71
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKD----KVAIKTIREGAMSE----EDFIEEAEVMMKLSHPKLVQLYGVCLeQAPICLVFEFM 438
Cdd:cd05040   1 EKLGDGSFGVVRRGEWTTPSgkviQVAVKCLKSDVLSQpnamDDFLKEVNAMHSLDHPNLIRLYGVVL-SSPLMMVTELA 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF--VLDDQYTSST 516
Cdd:cd05040  80 PLGSLLDRLRKDQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRAlpQNEDHYVMQE 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 GTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDI-STGFRLYKPRLASTHVYQIMNHCW 595
Cdd:cd05040 160 HRKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIdKEGERLERPDDCPQDIYNVMLQCW 239
                       250
                ....*....|....*....
gi 15718680 596 KERPEDRPAFSRLLRQLAE 614
Cdd:cd05040 240 AHKPADRPTFVALRDFLPE 258
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
7-148 2.18e-70

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 223.64  E-value: 2.18e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   7 LEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRIKCVEIVKSDISipCHYKYPFQVVHDN 86
Cdd:cd01238   1 LEGLLVKRSQGKKRFGPVNYKERWFVLTKSSLSYYEGDGEKRGKEKGSIDLSKVRCVEEVKDEAF--FERKYPFQVVYDD 78
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680  87 YLLYVFAPDRESRQRWVLALKEETRNNNSLVPKYHPNFWMDGKWRCCSQLEKLATGCAQYDP 148
Cdd:cd01238  79 YTLYVFAPSEEDRDEWIAALRKVCRNNSNLHDKYHPGFWTGGKWSCCGQTSKSAPGCQPAFD 140
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
358-612 2.71e-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: 228.22  E-value: 2.71e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDK----VAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPI 431
Cdd:cd05065   1 IDVSCVKIEEVIGAGEFGEVCRGRLKLPGKreifVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNIIHLEGVVTKSRPV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ 511
Cdd:cd05065  81 MIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 ----YTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHV 587
Cdd:cd05065 161 sdptYTSSLGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTAL 240
                       250       260
                ....*....|....*....|....*
gi 15718680 588 YQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05065 241 HQLMLDCWQKDRNLRPKFGQIVNTL 265
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
358-612 7.03e-70

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: 227.06  E-value: 7.03e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDK----VAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPI 431
Cdd:cd05066   1 IDASCIKIEKVIGAGEFGEVCSGRLKLPGKreipVAIKTLKAGYTEKQrrDFLSEASIMGQFDHPNIIHLEGVVTRSKPV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD- 510
Cdd:cd05066  81 MIVTEYMENGSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDp 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 --QYTsSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05066 161 eaAYT-TRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALH 239
                       250       260
                ....*....|....*....|....
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05066 240 QLMLDCWQKDRNERPKFEQIVSIL 263
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
356-608 9.22e-70

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: 226.83  E-value: 9.22e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQaPICLVF 435
Cdd:cd05073   6 WEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKE-PIYIIT 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd05073  85 EFMAKGSLLDFLKSDEGsKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTA 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 STGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHC 594
Cdd:cd05073 165 REGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRC 244
                       250
                ....*....|....
gi 15718680 595 WKERPEDRPAFSRL 608
Cdd:cd05073 245 WKNRPEERPTFEYI 258
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
356-608 1.96e-69

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: 226.49  E-value: 1.96e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQaPICLVF 435
Cdd:cd05071   4 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEE-PIYIVT 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd05071  83 EYMSKGSLLDFLKGEMGkYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 STGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHC 594
Cdd:cd05071 163 RQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLMCQC 242
                       250
                ....*....|....
gi 15718680 595 WKERPEDRPAFSRL 608
Cdd:cd05071 243 WRKEPEERPTFEYL 256
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
358-617 2.60e-69

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: 225.76  E-value: 2.60e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKD----KVAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQaPI 431
Cdd:cd05056   3 IQREDITLGRCIGEGQFGDVYQGVYMSPEnekiAVAVKTCKNCTSPSvrEKFLQEAYIMRQFDHPHIVKLIGVITEN-PV 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ 511
Cdd:cd05056  82 WIVMELAPLGELRSYLQVNKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMEDES 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIM 591
Cdd:cd05056 162 YYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLM 241
                       250       260
                ....*....|....*....|....*.
gi 15718680 592 NHCWKERPEDRPAFSRLLRQLAEIAE 617
Cdd:cd05056 242 TKCWAYDPSKRPRFTELKAQLSDILQ 267
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
358-615 6.80e-69

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: 224.85  E-value: 6.80e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDK----VAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPI 431
Cdd:cd05063   2 IHPSHITKQKVIGAGEFGEVFRGILKMPGRkevaVAIKTLKPGYTEKQrqDFLSEASIMGQFSHHNIIRLEGVVTKFKPA 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD- 510
Cdd:cd05063  82 MIITEYMENGALDKYLRDHDGEFSSYQLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLEDDp 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 --QYTSSTGtKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05063 162 egTYTTSGG-KIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSAVY 240
                       250       260
                ....*....|....*....|....*..
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05063 241 QLMLQCWQQDRARRPRFVDIVNLLDKL 267
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
356-613 1.60e-68

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: 223.21  E-value: 1.60e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWLNKdKVAIKTIReGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQApICLVF 435
Cdd:cd05083   1 WLLNLQKLTLGEIIGEGEFGAVLQGEYMGQ-KVAVKNIK-CDVTAQAFLEETAVMTKLQHKNLVRLLGVILHNG-LYIVM 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQ-RGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFvlddQYTS 514
Cdd:cd05083  78 ELMSKGNLVNFLRSRgRALVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKV----GSMG 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 STGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHC 594
Cdd:cd05083 154 VDNSRLPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMTSC 233
                       250
                ....*....|....*....
gi 15718680 595 WKERPEDRPAFSRLLRQLA 613
Cdd:cd05083 234 WEAEPGKRPSFKKLREKLE 252
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
232-340 3.10e-68

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, 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. It is crucial for the function of Tec PH domains and it's lack of presence in Txk 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: 198259  Cd Length: 108  Bit Score: 216.97  E-value: 3.10e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 232 NNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVvSENNPCIKHYHIKETNDNPKRYYVAEKY 311
Cdd:cd10396   1 NNLDQYEWYNKNINRSKAEKLLRDEGKEGGFMVRDSSQPGLYTVSLYTKAG-GEGNPCIRHYHIKETNDSPKKYYLAEKH 79
                        90       100
                ....*....|....*....|....*....
gi 15718680 312 VFDSIPLLINYHQHNGGGLVTRLRYPVCF 340
Cdd:cd10396  80 VFNSIPELIEYHKHNAAGLVTRLRYPVSS 108
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
363-602 5.58e-68

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: 222.73  E-value: 5.58e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYWLN----KDK--VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd05049   7 IVLKRELGEGAFGKVFLGECYNlepeQDKmlVAVKTLKDASSPDarKDFEREAELLTNLQHENIVKFYGVCTEGDPLLMV 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQ-------------RGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDF 501
Cdd:cd05049  87 FEYMEHGDLNKFLRSHgpdaaflasedsaPGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLVVKIGDF 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 502 GMTRFVLDDQYTSSTG-TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKP 580
Cdd:cd05049 167 GMSRDIYSTDYYRVGGhTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIECITQGRLLQRP 246
                       250       260
                ....*....|....*....|..
gi 15718680 581 RLASTHVYQIMNHCWKERPEDR 602
Cdd:cd05049 247 RTCPSEVYAVMLGCWKREPQQR 268
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
361-608 5.77e-66

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: 217.63  E-value: 5.77e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWLNKD------KVAIKTIREGAMS--EEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPIC 432
Cdd:cd05048   5 SAVRFLEELGEGAFGKVYKGELLGPSseesaiSVAIKTLKENASPktQQDFRREAELMSDLQHPNIVCLLGVCTKEQPQC 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYL---------------RTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIK 497
Cdd:cd05048  85 MLFEYMAHGDLHEFLvrhsphsdvgvssddDGTASSLDQSDFLHIAIQIAAGMEYLSSHHYVHRDLAARNCLVGDGLTVK 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 498 VSDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFR 576
Cdd:cd05048 165 ISDFGLSRDIYSsDYYRVQSKSLLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIEMIRSRQL 244
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 577 LYKPRLASTHVYQIMNHCWKERPEDRPAFSRL 608
Cdd:cd05048 245 LPCPEDCPARVYSLMVECWHEIPSRRPRFKEI 276
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
355-612 1.10e-64

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: 214.59  E-value: 1.10e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDK-------VAIKTIREGAMSEE--DFIEEAEvMMKL--SHPKLVQLYG 423
Cdd:cd05053   6 EWELPRDRLTLGKPLGEGAFGQVVKAEAVGLDNkpnevvtVAVKMLKDDATEKDlsDLVSEME-MMKMigKHKNIINLLG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 424 VCLEQAPICLVFEFMEHGCLSDYLRTQR---------------GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNC 488
Cdd:cd05053  85 ACTQDGPLYVVVEYASKGNLREFLRARRppgeeaspddprvpeEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAARNV 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 489 LVGENQVIKVSDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEV 567
Cdd:cd05053 165 LVTEDNVMKIADFGLARDIHHiDYYRKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEEL 244
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 15718680 568 VEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05053 245 FKLLKEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQLVEDL 289
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
361-614 2.47e-64

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: 213.74  E-value: 2.47e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHL------------GYWLNKDK-----VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQL 421
Cdd:cd05051   5 EKLEFVEKLGEGQFGEVHLceanglsdltsdDFIGNDNKdepvlVAVKMLRPDASKNarEDFLKEVKIMSQLKDPNIVRL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 422 YGVCLEQAPICLVFEFMEHGCLSDYLR-----------TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV 490
Cdd:cd05051  85 LGVCTRDEPLCMIVEYMENGDLNQFLQkheaetqgasaTNSKTLSYGTLLYMATQIASGMKYLESLNFVHRDLATRNCLV 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 491 GENQVIKVSDFGMTRFVLDDQYTSSTGTK-FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKI-PYENRSNSEVV 568
Cdd:cd05051 165 GPNYTIKIADFGMSRNLYSGDYYRIEGRAvLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCKEqPYEHLTDEQVI 244
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 15718680 569 EDISTGFR-------LYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05051 245 ENAGEFFRddgmevyLSRPPNCPKEIYELMLECWRRDEEDRPTFREIHLFLQR 297
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
368-602 1.14e-63

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: 211.36  E-value: 1.14e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYWLN----KDK--VAIKTIREGAMS-EEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd05092  12 ELGEGAFGKVFLAECHNllpeQDKmlVAVKALKEATESaRQDFQREAELLTVLQHQHIVRFYGVCTEGEPLIMVFEYMRH 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQ--------------RGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF 506
Cdd:cd05092  92 GDLNRFLRSHgpdakildggegqaPGQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVVKIGDFGMSRD 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 VLDDQYTSSTG-TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLAST 585
Cdd:cd05092 172 IYSTDYYRVGGrTMLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQGRELERPRTCPP 251
                       250
                ....*....|....*..
gi 15718680 586 HVYQIMNHCWKERPEDR 602
Cdd:cd05092 252 EVYAIMQGCWQREPQQR 268
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
365-612 7.15e-63

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: 209.69  E-value: 7.15e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVH----LGYWLNKDK--VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFE 436
Cdd:cd05050   9 YVRDIGQGAFGRVFqaraPGLLPYEPFtmVAVKMLKEEASADmqADFQREAALMAEFDHPNIVKLLGVCAVGKPMCLLFE 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGCLSDYLR----------TQRGLFAAE-----------TLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQV 495
Cdd:cd05050  89 YMAYGDLNEFLRhrspraqcslSHSTSSARKcglnplplsctEQLCIAKQVAAGMAYLSERKFVHRDLATRNCLVGENMV 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 496 IKVSDFGMTRFV-LDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd05050 169 VKIADFGLSRNIySADYYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHEEVIYYVRDG 248
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 15718680 575 FRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05050 249 NVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASINRIL 286
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
363-616 3.30e-62

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: 207.62  E-value: 3.30e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYWLNKD-----KVAIKTIR--EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP--ICL 433
Cdd:cd05038   6 LKFIKQLGEGHFGSVELCRYDPLGdntgeQVAVKSLQpsGEEQHMSDFKREIEILRTLDHEYIVKYKGVCESPGRrsLRL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL--DDQ 511
Cdd:cd05038  86 IMEYLPSGSLRDYLQRHRDQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPedKEY 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNS--------------EVVEDISTGFRL 577
Cdd:cd05038 166 YYVKEPGESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPSQSPPALFlrmigiaqgqmivtRLLELLKSGERL 245
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 15718680 578 YKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd05038 246 PRPPSCPDEVYDLMKECWEYEPQDRPSFSDLILIIDRLR 284
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
369-617 4.68e-61

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: 204.12  E-value: 4.68e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVhLGYWLNKD----KVAIKTIREGAMSEE--DFIEEAEVMMKLS-HPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd05047   3 IGEGNFGQV-LKARIKKDglrmDAAIKRMKEYASKDDhrDFAGELEVLCKLGhHPNIINLLGACEHRGYLYLAIEYAPHG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGL---------------FAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF 506
Cdd:cd05047  82 NLLDFLRKSRVLetdpafaianstastLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 vlDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTH 586
Cdd:cd05047 162 --QEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDE 239
                       250       260       270
                ....*....|....*....|....*....|.
gi 15718680 587 VYQIMNHCWKERPEDRPAFSRLLRQLAEIAE 617
Cdd:cd05047 240 VYDLMRQCWREKPYERPSFAQILVSLNRMLE 270
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
369-615 7.58e-61

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: 203.09  E-value: 7.58e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKD----KVAIKTI-REGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCL--EQAPIcLVFEFMEH 440
Cdd:cd05058   3 IGKGHFGCVYHGTLIDSDgqkiHCAVKSLnRITDIEEvEQFLKEGIIMKDFSHPNVLSLLGICLpsEGSPL-VVLPYMKH 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS---STG 517
Cdd:cd05058  82 GDLRNFIRSETHNPTVKDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARDIYDKEYYSvhnHTG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKE 597
Cdd:cd05058 162 AKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVMLSCWHP 241
                       250
                ....*....|....*...
gi 15718680 598 RPEDRPAFSRLLRQLAEI 615
Cdd:cd05058 242 KPEMRPTFSELVSRISQI 259
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
357-616 6.31e-60

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: 201.41  E-value: 6.31e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSELTFVQEIGSGQFGLVHLGYWLN-----KDKVAIKTIREGA--MSEEDFIEEAEVMMKLSHPKLVQLYGVCLeQA 429
Cdd:cd05109   3 ILKETELKKVKVLGSGAFGTVYKGIWIPdgenvKIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVCRLLGICL-TS 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV-L 508
Cdd:cd05109  82 TVQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdI 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05109 162 DETEYHADGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVY 241
                       250       260
                ....*....|....*....|....*...
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd05109 242 MIMVKCWMIDSECRPRFRELVDEFSRMA 269
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
232-339 1.28e-59

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: 194.16  E-value: 1.28e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 232 NNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVvseNNPCIKHYHIKETNDNPkrYYVAEKY 311
Cdd:cd09934   1 LNLEKYEWYVGDMSRQRAESLLKQEDKEGCFVVRNSSTKGLYTVSLFTKVP---GSPHVKHYHIKQNARSE--FYLAEKH 75
                        90       100
                ....*....|....*....|....*...
gi 15718680 312 VFDSIPLLINYHQHNGGGLVTRLRYPVC 339
Cdd:cd09934  76 CFETIPELINYHQHNSGGLATRLKYPVC 103
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
362-618 4.65e-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: 199.08  E-value: 4.65e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYwLNKD----KVAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLEQ------ 428
Cdd:cd05075   1 KLALGKTLGEGEFGSVMEGQ-LNQDdsvlKVAVKTMKIAICTRsemEDFLSEAVCMKEFDHPNVMRLIGVCLQNtesegy 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 429 -APIcLVFEFMEHGCLSDYLRTQR-----GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG 502
Cdd:cd05075  80 pSPV-VILPFMKHGDLHSFLLYSRlgdcpVYLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFG 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 503 MTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPR 581
Cdd:cd05075 159 LSKKIYNgDYYRQGRISKMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPP 238
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 15718680 582 LASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd05075 239 DCLDGLYELMSSCWLLNPKDRPSFETLRCELEKILKD 275
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
369-614 9.07e-59

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: 198.07  E-value: 9.07e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK------VAIKTI--REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd05046  13 LGRGEFGEVFLAKAKGIEEeggetlVLVKALqkTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCREAEPHYMILEYTDL 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQRGL--------FAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd05046  93 GDLKQFLRATKSKdeklkpppLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSKDVYNSEY 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTG-FRLYKPRLASTHVYQIM 591
Cdd:cd05046 173 YKLRNALIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLQAGkLELPVPEGCPSRLYKLM 252
                       250       260
                ....*....|....*....|...
gi 15718680 592 NHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05046 253 TRCWAVNPKDRPSFSELVSALGE 275
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
362-618 5.37e-58

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: 196.76  E-value: 5.37e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVhLGYWLNKD----KVAIKTIREGAMSEE--DFIEEAEVMMKLS-HPKLVQLYGVCLEQAPICLV 434
Cdd:cd05089   3 DIKFEDVIGEGNFGQV-IKAMIKKDglkmNAAIKMLKEFASENDhrDFAGELEVLCKLGhHPNIINLLGACENRGYLYIA 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRGL-----FAAE----------TLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVS 499
Cdd:cd05089  82 IEYAPYGNLLDFLRKSRVLetdpaFAKEhgtastltsqQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIA 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 500 DFGMTRFvlDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYK 579
Cdd:cd05089 162 DFGLSRG--EEVYVKKTMGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEK 239
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 15718680 580 PRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd05089 240 PRNCDDEVYELMRQCWRDRPYERPPFSQISVQLSRMLEA 278
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
368-606 1.24e-57

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: 194.41  E-value: 1.24e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYWLNKDK---VAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVClEQAPICLVFEFMEHG 441
Cdd:cd05116   2 ELGSGNFGTVKKGYYQMKKVvktVAVKILKNEANDPalkDELLREANVMQQLDNPYIVRMIGIC-EAESWMLVMEMAELG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ--YTSSTGTK 519
Cdd:cd05116  81 PLNKFLQKNRHV-TEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADEnyYKAQTHGK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 520 FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERP 599
Cdd:cd05116 160 WPVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYDV 239

                ....*..
gi 15718680 600 EDRPAFS 606
Cdd:cd05116 240 DERPGFA 246
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
357-616 1.56e-57

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: 196.40  E-value: 1.56e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSELTFVQEIGSGQFGLVHLGYWLN-----KDKVAIKTIREGA--MSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQA 429
Cdd:cd05108   3 ILKETEFKKIKVLGSGAFGTVYKGLWIPegekvKIPVAIKELREATspKANKEILDEAYVMASVDNPHVCRLLGICLTST 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 pICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV-L 508
Cdd:cd05108  83 -VQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLgA 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05108 162 EEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVY 241
                       250       260
                ....*....|....*....|....*...
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd05108 242 MIMVKCWMIDADSRPKFRELIIEFSKMA 269
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
358-602 2.79e-57

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: 194.84  E-value: 2.79e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLN----KDK--VAIKTIREGAMS-EEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP 430
Cdd:cd05094   2 IKRRDIVLKRELGEGAFGKVFLAECYNlsptKDKmlVAVKTLKDPTLAaRKDFQREAELLTNLQHDHIVKFYGVCGDGDP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGCLSDYLRTQ---------------RGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQV 495
Cdd:cd05094  82 LIMVFEYMKHGDLNKFLRAHgpdamilvdgqprqaKGELGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLL 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 496 IKVSDFGMTRFVLDDQYTSSTG-TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd05094 162 VKIGDFGMSRDVYSTDYYRVGGhTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECITQG 241
                       250       260
                ....*....|....*....|....*...
gi 15718680 575 FRLYKPRLASTHVYQIMNHCWKERPEDR 602
Cdd:cd05094 242 RVLERPRVCPKEVYDIMLGCWQREPQQR 269
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
364-610 8.51e-57

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 191.97  E-value: 8.51e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    364 TFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:smart00220   2 EILEKLGEGSFGKVYLARDKKTGKlVAIKVIKKKKIKKdrERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEG 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    441 GCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ-YTSSTGTK 519
Cdd:smart00220  82 GDLFDLLK-KRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGEkLTTFVGTP 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    520 FpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYKPR---LASTHVYQIMNHCWK 596
Cdd:smart00220 161 E---YMAPEVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDDQLLELFKKIGKPKPPFPPpewDISPEAKDLIRKLLV 236
                          250
                   ....*....|....
gi 15718680    597 ERPEDRPAFSRLLR 610
Cdd:smart00220 237 KDPEKRLTAEEALQ 250
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
355-616 8.94e-57

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: 193.86  E-value: 8.94e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLV--HLGYWLNKD----KVAIKTIREGAMSEED--FIEEAEVMMKL-SHPKLVQLYGVC 425
Cdd:cd05055  29 KWEFPRNNLSFGKTLGAGAFGKVveATAYGLSKSdavmKVAVKMLKPTAHSSEReaLMSELKIMSHLgNHENIVNLLGAC 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LEQAPICLVFEFMEHGCLSDYLRTQRGLFAA-ETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMT 504
Cdd:cd05055 109 TIGGPILVITEYCCYGDLLNFLRRKRESFLTlEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKICDFGLA 188
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 505 RFVLDD-QYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRS-NSEVVEDISTGFRLYKPRL 582
Cdd:cd05055 189 RDIMNDsNYVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMPvDSKFYKLIKEGYRMAQPEH 268
                       250       260       270
                ....*....|....*....|....*....|....
gi 15718680 583 ASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd05055 269 APAEIYDIMKTCWDADPLKRPTFKQIVQLIGKQL 302
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
369-615 1.19e-56

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: 192.36  E-value: 1.19e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYwLNKD-----KVAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLEQA-----PICLV- 434
Cdd:cd05035   7 LGEGEFGSVMEAQ-LKQDdgsqlKVAVKTMKVDIHTYseiEEFLSEAACMKDFDHPNVMRLIGVCFTASdlnkpPSPMVi 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQR-----GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD 509
Cdd:cd05035  86 LPFMKHGDLHSYLLYSRlgglpEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLSRKIYS 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 -DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05035 166 gDYYRQGRISKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPEDCLDEVY 245
                       250       260
                ....*....|....*....|....*..
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05035 246 FLMYFCWTVDPKDRPTFTKLREVLENI 272
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
369-615 1.66e-56

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: 192.87  E-value: 1.66e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLV------HLGYWLNKDKVAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd05045   8 LGEGEFGKVvkatafRLKGRAGYTTVAVKMLKENASSSElrDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAKY 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQR----------------GLFAAET-------LLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIK 497
Cdd:cd05045  88 GSLRSFLRESRkvgpsylgsdgnrnssYLDNPDEraltmgdLISFAWQISRGMQYLAEMKLVHRDLAARNVLVAEGRKMK 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 498 VSDFGMTRFVL-DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFR 576
Cdd:cd05045 168 ISDFGLSRDVYeEDSYVKRSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFNLLKTGYR 247
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 15718680 577 LYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05045 248 MERPENCSEEMYNLMLTCWKQEPDKRPTFADISKELEKM 286
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
357-616 5.75e-56

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: 191.82  E-value: 5.75e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSELTFVQEIGSGQFGLVHLGYWLN-----KDKVAIKTIRE--GAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQA 429
Cdd:cd05110   3 ILKETELKRVKVLGSGAFGTVYKGIWVPegetvKIPVAIKILNEttGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPT 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 pICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL- 508
Cdd:cd05110  83 -IQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEg 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05110 162 DEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVY 241
                       250       260
                ....*....|....*....|....*...
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd05110 242 MVMVKCWMIDADSRPKFKELAAEFSRMA 269
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
358-608 7.03e-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: 190.13  E-value: 7.03e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGyWLN-----KDKVAIKTIREGAMSEED--FIEEAEVMMKLSHPKLVQLYGVCLEQAP 430
Cdd:cd05064   2 LDNKSIKIERILGTGRFGELCRG-CLKlpskrELPVAIHTLRAGCSDKQRrgFLAEALTLGQFDHSNIVRLEGVITRGNT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG-MTRFVLD 509
Cdd:cd05064  81 MMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRrLQEDKSE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGtKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQ 589
Cdd:cd05064 161 AIYTTMSG-KSPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLHQ 239
                       250
                ....*....|....*....
gi 15718680 590 IMNHCWKERPEDRPAFSRL 608
Cdd:cd05064 240 LMLDCWQKERGERPRFSQI 258
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
367-618 7.81e-56

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: 191.02  E-value: 7.81e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLG--YWLNKDK----VAIKTIREGAMS-EEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd05093  11 RELGEGAFGKVFLAecYNLCPEQdkilVAVKTLKDASDNaRKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMK 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQ--RGLFAAE----------TLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV 507
Cdd:cd05093  91 HGDLNKFLRAHgpDAVLMAEgnrpaeltqsQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDV 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 508 LDDQYTSSTG-TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTH 586
Cdd:cd05093 171 YSTDYYRVGGhTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPKE 250
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 587 VYQIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd05093 251 VYDLMLGCWQREPHMRLNIKEIHSLLQNLAKA 282
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
357-618 2.11e-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: 189.38  E-value: 2.11e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSELTFVQEIGSGQFGLVHLGYWLNKD----KVAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLEQA 429
Cdd:cd14204   3 MIDRNLLSLGKVLGEGEFGSVMEGELQQPDgtnhKVAVKTMKLDNFSQreiEEFLSEAACMKDFNHPNVIRLLGVCLEVG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 P-----ICLVFEFMEHGCLSDYLRTQR-----GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVS 499
Cdd:cd14204  83 SqripkPMVILPFMKYGDLHSFLLRSRlgsgpQHVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 500 DFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLY 578
Cdd:cd14204 163 DFGLSKKIYSgDYYRQGRIAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHRLK 242
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 15718680 579 KPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd14204 243 QPEDCLDELYDIMYSCWRSDPTDRPTFTQLRENLEKLLES 282
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
355-615 4.06e-55

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: 189.79  E-value: 4.06e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLV--HLGYWLNKDK------VAIKTIREGAMSEE--DFIEEAEvMMKL--SHPKLVQLY 422
Cdd:cd05099   6 KWEFPRDRLVLGKPLGEGCFGQVvrAEAYGIDKSRpdqtvtVAVKMLKDNATDKDlaDLISEME-LMKLigKHKNIINLL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 423 GVCLEQAPICLVFEFMEHGCLSDYLRTQR---------------GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN 487
Cdd:cd05099  85 GVCTQEGPLYVIVEYAAKGNLREFLRARRppgpdytfditkvpeEQLSFKDLVSCAYQVARGMEYLESRRCIHRDLAARN 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 488 CLVGENQVIKVSDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFsFSR-YSSKSDVWSFGVLMWEVFSEGKIPYENRSNS 565
Cdd:cd05099 165 VLVTEDNVMKIADFGLARGVHDiDYYKKTSNGRLPVKWMAPEAL-FDRvYTHQSDVWSFGILMWEIFTLGGSPYPGIPVE 243
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 15718680 566 EVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05099 244 ELFKLLREGHRMDKPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKV 293
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
355-615 4.73e-55

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: 188.85  E-value: 4.73e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDK------VAIKTIREGAMSEED--FIEEAEVMMKLS-HPKLVQLYGVC 425
Cdd:cd05054   1 KWEFPRDRLKLGKPLGRGAFGKVIQASAFGIDKsatcrtVAVKMLKEGATASEHkaLMTELKILIHIGhHLNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LEQ-APICLVFEFMEHGCLSDYLRTQRGLFAA-------------------------ETLLGMCLDVCEGMAYLEEACVI 479
Cdd:cd05054  81 TKPgGPLMVIVEFCKFGNLSNYLRSKREEFVPyrdkgardveeeedddelykepltlEDLICYSFQVARGMEFLASRKCI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 480 HRDLAARNCLVGENQVIKVSDFGMTRFVLDD-QYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIP 558
Cdd:cd05054 161 HRDLAARNILLSENNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASP 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 559 YEN-RSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05054 241 YPGvQMDEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTFSELVEKLGDL 298
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
368-605 6.89e-55

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: 187.85  E-value: 6.89e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYWLNKDK---VAIKTIREGAMS--EEDFIEEAEVMMKLSHPKLVQLYGVClEQAPICLVFEFMEHGC 442
Cdd:cd05115  11 ELGSGNFGCVKKGVYKMRKKqidVAIKVLKQGNEKavRDEMMREAQIMHQLDNPYIVRMIGVC-EAEALMLVMEMASGGP 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL--DDQYTSSTGTKF 520
Cdd:cd05115  90 LNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGadDSYYKARSAGKW 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 PVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPE 600
Cdd:cd05115 170 PLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSDCWIYKWE 249

                ....*
gi 15718680 601 DRPAF 605
Cdd:cd05115 250 DRPNF 254
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
356-614 1.13e-54

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: 187.87  E-value: 1.13e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGywLNKD--------KVAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVC 425
Cdd:cd05061   1 WEVSREKITLLRELGQGSFGMVYEG--NARDiikgeaetRVAVKTVNESASLREriEFLNEASVMKGFTCHHVVRLLGVV 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LEQAPICLVFEFMEHGCLSDYLRTQRG---------LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVI 496
Cdd:cd05061  79 SKGQPTLVVMELMAHGDLKSYLRSLRPeaennpgrpPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTV 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 497 KVSDFGMTRFVLDDQYTSSTGTKF-PVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGF 575
Cdd:cd05061 159 KIGDFGMTRDIYETDYYRKGGKGLlPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGG 238
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 15718680 576 RLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05061 239 YLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKD 277
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
357-615 2.02e-54

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: 187.05  E-value: 2.02e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSELTFVQEIGSGQFGLVHLGYWLNKD----KVAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLE-- 427
Cdd:cd05074   5 LIQEQQFTLGRMLGKGEFGSVREAQLKSEDgsfqKVAVKMLKADIFSSsdiEEFLREAACMKEFDHPNVIKLIGVSLRsr 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 428 ---QAPICLV-FEFMEHGCLSDYLRTQR-----GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKV 498
Cdd:cd05074  85 akgRLPIPMViLPFMKHGDLHTFLLMSRigeepFTLPLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCV 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 499 SDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRL 577
Cdd:cd05074 165 ADFGLSKKIYSgDYYRQGCASKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGNRL 244
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 15718680 578 YKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05074 245 KQPPDCLEDVYELMCQCWSPEPKCRPSFQHLRDQLELI 282
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
357-616 3.52e-54

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: 185.93  E-value: 3.52e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSELTFVQEIGSGQFGLVHLGYWLN-----KDKVAIKTI--REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVClEQA 429
Cdd:cd05111   3 IFKETELRKLKVLGSGVFGTVHKGIWIPegdsiKIPVAIKVIqdRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGIC-PGA 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL- 508
Cdd:cd05111  82 SLQLVTQLLPLGSLLDHVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLYp 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVY 588
Cdd:cd05111 162 DDKKYFYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQICTIDVY 241
                       250       260
                ....*....|....*....|....*...
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd05111 242 MVMVKCWMIDENIRPTFKELANEFTRMA 269
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
357-617 6.49e-54

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: 186.36  E-value: 6.49e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSELTFVQEIGSGQFGLVhLGYWLNKDKV----AIKTIREGAMSEE--DFIEEAEVMMKLS-HPKLVQLYGVCLEQA 429
Cdd:cd05088   3 VLEWNDIKFQDVIGEGNFGQV-LKARIKKDGLrmdaAIKRMKEYASKDDhrDFAGELEVLCKLGhHPNIINLLGACEHRG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEHGCLSDYLRTQRGL---------------FAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ 494
Cdd:cd05088  82 YLYLAIEYAPHGNLLDFLRKSRVLetdpafaianstastLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENY 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 495 VIKVSDFGMTRFvlDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd05088 162 VAKIADFGLSRG--QEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQG 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 15718680 575 FRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAE 617
Cdd:cd05088 240 YRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLE 282
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
363-614 7.90e-54

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: 185.58  E-value: 7.90e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHL----GYWLNKDK-------------VAIKTIREGAM--SEEDFIEEAEVMMKLSHPKLVQLYG 423
Cdd:cd05095   7 LTFKEKLGEGQFGEVHLceaeGMEKFMDKdfalevsenqpvlVAVKMLRADANknARNDFLKEIKIMSRLKDPNIIRLLA 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 424 VCLEQAPICLVFEFMEHGCLSDYLRTQRG----LFAAETLLG-------MCLDVCEGMAYLEEACVIHRDLAARNCLVGE 492
Cdd:cd05095  87 VCITDDPLCMITEYMENGDLNQFLSRQQPegqlALPSNALTVsysdlrfMAAQIASGMKYLSSLNFVHRDLATRNCLVGK 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 493 NQVIKVSDFGMTRFVLDDQYTSSTGTK-FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGK-IPYENRSNSEVVED 570
Cdd:cd05095 167 NYTIKIADFGMSRNLYSGDYYRIQGRAvLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFCReQPYSQLSDEQVIEN 246
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 571 ISTGFR-------LYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05095 247 TGEFFRdqgrqtyLPQPALCPDSVYKLMLSCWRRDTKDRPSFQEIHTLLQE 297
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
361-614 8.48e-53

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: 183.21  E-value: 8.48e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHL------------GYWLNKDK-----VAIKTIREGAM--SEEDFIEEAEVMMKLSHPKLVQL 421
Cdd:cd05096   5 GHLLFKEKLGEGQFGEVHLcevvnpqdlptlQFPFNVRKgrpllVAVKILRPDANknARNDFLKEVKILSRLKDPNIIRL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 422 YGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAE------------------TLLGMCLDVCEGMAYLEEACVIHRDL 483
Cdd:cd05096  85 LGVCVDEDPLCMITEYMENGDLNQFLSSHHLDDKEEngndavppahclpaisysSLLHVALQIASGMKYLSSLNFVHRDL 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 484 AARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTK-FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKI-PYEN 561
Cdd:cd05096 165 ATRNCLVGENLTIKIADFGMSRNLYAGDYYRIQGRAvLPIRWMAWECILMGKFTTASDVWAFGVTLWEILMLCKEqPYGE 244
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 562 RSNSEVVEDISTGFR-------LYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05096 245 LTDEQVIENAGEFFRdqgrqvyLFRPPPCPQGLYELMLQCWSRDCRERPSFSDIHAFLTE 304
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
362-614 2.30e-52

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: 181.71  E-value: 2.30e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHL----------GYWLNKDK-----VAIKTIREGAMS--EEDFIEEAEVMMKLSHPKLVQLYGV 424
Cdd:cd05097   6 QLRLKEKLGEGQFGEVHLceaeglaeflGEGAPEFDgqpvlVAVKMLRADVTKtaRNDFLKEIKIMSRLKNPNIIRLLGV 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 425 CLEQAPICLVFEFMEHGCLSDYLrTQRGLFAAET------------LLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGE 492
Cdd:cd05097  86 CVSDDPLCMITEYMENGDLNQFL-SQREIESTFThannipsvsianLLYMAVQIASGMKYLASLNFVHRDLATRNCLVGN 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 493 NQVIKVSDFGMTRFVLDDQYTSSTGTK-FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGK-IPYENRSNSEVVED 570
Cdd:cd05097 165 HYTIKIADFGMSRNLYSGDYYRIQGRAvLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLCKeQPYSLLSDEQVIEN 244
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 571 ISTGFR-------LYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05097 245 TGEFFRnqgrqiyLSQTPLCPSPVFKLMMRCWSRDIKDRPTFNKIHHFLRE 295
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
369-612 8.61e-52

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: 177.46  E-value: 8.61e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 445
Cdd:cd00180   1 LGKGSFGKVYKARDKETGKkVAVKVIPKEKLKKllEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD-DQYTSSTGTKFPVKW 524
Cdd:cd00180  81 LLKENKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSdDSLLKTTGGTTPPYY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 525 ASPEVFSFSRYSSKSDVWSFGVLMWEVfsegkipyenrsnsevvedistgfrlykprlasTHVYQIMNHCWKERPEDRPA 604
Cdd:cd00180 161 APPELLGGRYYGPKVDIWSLGVILYEL---------------------------------EELKDLIRRMLQYDPKKRPS 207

                ....*...
gi 15718680 605 FSRLLRQL 612
Cdd:cd00180 208 AKELLEHL 215
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
355-615 9.78e-52

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: 180.60  E-value: 9.78e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDK--------VAIKTIREGAMSEE--DFIEEAEvMMKL--SHPKLVQLY 422
Cdd:cd05101  18 KWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKdkpkeavtVAVKMLKDDATEKDlsDLVSEME-MMKMigKHKNIINLL 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 423 GVCLEQAPICLVFEFMEHGCLSDYLRTQRGL---------------FAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN 487
Cdd:cd05101  97 GACTQDGPLYVIVEYASKGNLREYLRARRPPgmeysydinrvpeeqMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARN 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 488 CLVGENQVIKVSDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSE 566
Cdd:cd05101 177 VLVTENNVMKIADFGLARDINNiDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEE 256
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 567 VVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05101 257 LFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI 305
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
355-615 2.85e-51

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: 179.05  E-value: 2.85e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDK--------VAIKTIREGAMSEE--DFIEEAEvMMKL--SHPKLVQLY 422
Cdd:cd05098   7 RWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKdkpnrvtkVAVKMLKSDATEKDlsDLISEME-MMKMigKHKNIINLL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 423 GVCLEQAPICLVFEFMEHGCLSDYLRTQR---------------GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN 487
Cdd:cd05098  86 GACTQDGPLYVIVEYASKGNLREYLQARRppgmeycynpshnpeEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARN 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 488 CLVGENQVIKVSDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSE 566
Cdd:cd05098 166 VLVTEDNVMKIADFGLARDIHHiDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEE 245
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 567 VVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05098 246 LFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI 294
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
361-605 3.75e-51

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: 178.28  E-value: 3.75e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLG--YWLNKDK---VAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICL 433
Cdd:cd05090   5 SAVRFMEELGECAFGKIYKGhlYLPGMDHaqlVAIKTLKDYNNPQQwnEFQQEASLMTELHHPNIVCLLGVVTQEQPVCM 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHG----------------CLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIK 497
Cdd:cd05090  85 LFEFMNQGdlheflimrsphsdvgCSSDEDGTVKSSLDHGDFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQLHVK 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 498 VSDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFR 576
Cdd:cd05090 165 ISDLGLSREIYSsDYYRVQNKSLLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVRKRQL 244
                       250       260
                ....*....|....*....|....*....
gi 15718680 577 LYKPRLASTHVYQIMNHCWKERPEDRPAF 605
Cdd:cd05090 245 LPCSEDCPPRMYSLMTECWQEIPSRRPRF 273
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
355-615 1.52e-50

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: 178.29  E-value: 1.52e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDK--------VAIKTIREGAMSEE--DFIEEAEvMMKL--SHPKLVQLY 422
Cdd:cd05100   6 KWELSRTRLTLGKPLGEGCFGQVVMAEAIGIDKdkpnkpvtVAVKMLKDDATDKDlsDLVSEME-MMKMigKHKNIINLL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 423 GVCLEQAPICLVFEFMEHGCLSDYLRTQR--GL-------------FAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN 487
Cdd:cd05100  85 GACTQDGPLYVLVEYASKGNLREYLRARRppGMdysfdtcklpeeqLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARN 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 488 CLVGENQVIKVSDFGMTRFVLD-DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSE 566
Cdd:cd05100 165 VLVTEDNVMKIADFGLARDVHNiDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEE 244
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 567 VVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05100 245 LFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRV 293
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
358-612 6.83e-50

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: 174.82  E-value: 6.83e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWL------NKDKVAIKTIR---EGAMSEEdFIEEAEVMMKLSHPKLVQLYGVCLEQ 428
Cdd:cd05091   3 INLSAVRFMEELGEDRFGKVYKGHLFgtapgeQTQAVAIKTLKdkaEGPLREE-FRHEAMLRSRLQHPNIVCLLGVVTKE 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 429 APICLVFEFMEHGCLSDYL---------------RTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGEN 493
Cdd:cd05091  82 QPMSMIFSYCSHGDLHEFLvmrsphsdvgstdddKTVKSTLEPADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFDK 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 494 QVIKVSDFGMTRFVLDDQYTSSTGTK-FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDIS 572
Cdd:cd05091 162 LNVKISDLGLFREVYAADYYKLMGNSlLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVIEMIR 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 15718680 573 TGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05091 242 NRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRFKDIHSRL 281
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
356-614 9.15e-49

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: 171.37  E-value: 9.15e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGY--WLNKD----KVAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLE 427
Cdd:cd05062   1 WEVAREKITMSRELGQGSFGMVYEGIakGVVKDepetRVAIKTVNEAASMREriEFLNEASVMKEFNCHHVVRLLGVVSQ 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 428 QAPICLVFEFMEHGCLSDYLRTQR---------GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKV 498
Cdd:cd05062  81 GQPTLVIMELMTRGDLKSYLRSLRpemennpvqAPPSLKKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 499 SDFGMTRFVLDDQYTSSTGTKF-PVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRL 577
Cdd:cd05062 161 GDFGMTRDIYETDYYRKGGKGLlPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGLL 240
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 15718680 578 YKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05062 241 DKPDNCPDMLFELMRMCWQYNPKMRPSFLEIISSIKE 277
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
369-615 7.34e-48

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: 168.34  E-value: 7.34e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNkDKVAIKTIR-----EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14061   2 IGVGGFGKVYRGIWRG-EEVAVKAARqdpdeDISVTLENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGAL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRglFAAETLLGMCLDVCEGMAYL-EEACV--IHRDLAARNCLVGE--------NQVIKVSDFGMTRFVLDDQY 512
Cdd:cd14061  81 NRVLAGRK--IPPHVLVDWAIQIARGMNYLhNEAPVpiIHRDLKSSNILILEaienedleNKTLKITDFGLAREWHKTTR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG-FRLYKPRLASTHVYQIM 591
Cdd:cd14061 159 MSAAGT---YAWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKGIDGLAVAYGVAVNkLTLPIPSTCPEPFAQLM 234
                       250       260
                ....*....|....*....|....
gi 15718680 592 NHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14061 235 KDCWQPDPHDRPSFADILKQLENI 258
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
355-615 1.35e-47

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: 170.18  E-value: 1.35e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLV--HLGYWLNKDK----VAIKTIREGAMSEE--DFIEEAEVMMKLSHP-KLVQLYGVC 425
Cdd:cd14207   1 KWEFARERLKLGKSLGRGAFGKVvqASAFGIKKSPtcrvVAVKMLKEGATASEykALMTELKILIHIGHHlNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LEQA-PICLVFEFMEHGCLSDYLRTQRGLFAA------------------------------------------------ 456
Cdd:cd14207  81 TKSGgPLMVIVEYCKYGNLSNYLKSKRDFFVTnkdtslqeelikekkeaeptggkkkrlesvtssesfassgfqedksls 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 457 -------------------ETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD-QYTSST 516
Cdd:cd14207 161 dveeeeedsgdfykrpltmEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNpDYVRKG 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 GTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYEN-RSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCW 595
Cdd:cd14207 241 DARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGvQIDEDFCSKLKEGIRMRAPEFATSEIYQIMLDCW 320
                       330       340
                ....*....|....*....|
gi 15718680 596 KERPEDRPAFSRLLRQLAEI 615
Cdd:cd14207 321 QGDPNERPRFSELVERLGDL 340
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
369-619 1.20e-46

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: 164.92  E-value: 1.20e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDkVAIKTIrEGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLR 448
Cdd:cd14058   1 VGRGSFGVVCKARWRNQI-VAVKII-ESESEKKAFEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGSLYNVLH 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 449 TQRGL--FAAETLLGMCLDVCEGMAYL---EEACVIHRDLAARNCLVGEN-QVIKVSDFGMTRfvldDQYTSSTGTKFPV 522
Cdd:cd14058  79 GKEPKpiYTAAHAMSWALQCAKGVAYLhsmKPKALIHRDLKPPNLLLTNGgTVLKICDFGTAC----DISTHMTNNKGSA 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 523 KWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKiPYEN--RSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPE 600
Cdd:cd14058 155 AWMAPEVFEGSKYSEKCDVFSWGIILWEVITRRK-PFDHigGPAFRIMWAVHNGERPPLIKNCPKPIESLMTRCWSKDPE 233
                       250
                ....*....|....*....
gi 15718680 601 DRPAFSRLLRQLAEIAESG 619
Cdd:cd14058 234 KRPSMKEIVKIMSHLMQFF 252
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
355-615 3.08e-46

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: 166.31  E-value: 3.08e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLV--HLGYWLNK----DKVAIKTIREGAMSEED--FIEEAEVMMKL-SHPKLVQLYGVC 425
Cdd:cd05102   1 QWEFPRDRLRLGKVLGHGAFGKVveASAFGIDKssscETVAVKMLKEGATASEHkaLMSELKILIHIgNHLNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LE-QAPICLVFEFMEHGCLSDYLRTQRGLFAA------------------------------------------------ 456
Cdd:cd05102  81 TKpNGPLMVIVEFCKYGNLSNFLRAKREGFSPyrersprtrsqvrsmveavradrrsrqgsdrvasftestsstnqprqe 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 457 -----------ETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD-QYTSSTGTKFPVKW 524
Cdd:cd05102 161 vddlwqspltmEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDpDYVRKGSARLPLKW 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 525 ASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYEN-RSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRP 603
Cdd:cd05102 241 MAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGvQINEEFCQRLKDGTRMRAPEYATPEIYRIMLSCWHGDPKERP 320
                       330
                ....*....|..
gi 15718680 604 AFSRLLRQLAEI 615
Cdd:cd05102 321 TFSDLVEILGDL 332
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
355-618 6.88e-45

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: 162.84  E-value: 6.88e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDK------VAIKTIREGAMSEED--FIEEAEVMMKLSHP-KLVQLYGVC 425
Cdd:cd05103   1 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKtatcrtVAVKMLKEGATHSEHraLMSELKILIHIGHHlNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LEQA-PICLVFEFMEHGCLSDYLRTQRGLFAA------------------------------------------------ 456
Cdd:cd05103  81 TKPGgPLMVIVEFCKFGNLSAYLRSKRSEFVPyktkgarfrqgkdyvgdisvdlkrrldsitssqssassgfveekslsd 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 457 ------------------ETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD-QYTSSTG 517
Cdd:cd05103 161 veeeeagqedlykdfltlEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDpDYVRKGD 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYEN-RSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWK 596
Cdd:cd05103 241 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 320
                       330       340
                ....*....|....*....|..
gi 15718680 597 ERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd05103 321 GEPSQRPTFSELVEHLGNLLQA 342
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
363-615 3.94e-44

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: 159.03  E-value: 3.94e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYW--LNKDK---VAIKTIREGamSEE---DFIEEAEVMMKLSHPKLVQLYGVCLE--QAPIC 432
Cdd:cd14205   6 LKFLQQLGKGNFGSVEMCRYdpLQDNTgevVAVKKLQHS--TEEhlrDFEREIEILKSLQHDNIVKYKGVCYSagRRNLR 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ- 511
Cdd:cd14205  84 LIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKe 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 -YTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSegkipYENRSNS--------------------EVVED 570
Cdd:cd14205 164 yYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFT-----YIEKSKSppaefmrmigndkqgqmivfHLIEL 238
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 15718680 571 ISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14205 239 LKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQI 283
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
366-614 1.85e-43

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: 157.23  E-value: 1.85e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEigsGQFGLVHLGYWLNKD----KVAIKTIREGAmSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQ-APICLVFEF 437
Cdd:cd05043  14 LQE---GTFGRIFHGILRDEKgkeeEVLVKTVKDHA-SEIQvtmLLQESSLLYGLSHQNLLPILHVCIEDgEKPMVLYPY 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQR-----GLFAAET--LLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD 510
Cdd:cd05043  90 MNWGNLKLFLQQCRlseanNPQALSTqqLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALSRDLFPM 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 QYTS-STGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQ 589
Cdd:cd05043 170 DYHClGDNENRPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQPINCPDELFA 249
                       250       260
                ....*....|....*....|....*
gi 15718680 590 IMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05043 250 VMACCWALDPEERPSFQQLVQCLTD 274
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
356-609 3.63e-43

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: 159.79  E-value: 3.63e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLV-----H-LGYWLNKDKVAIKTIREGAMSEED--FIEEAEVMMKLS-HPKLVQLYGVCL 426
Cdd:cd05107  32 WEMPRDNLVLGRTLGSGAFGRVveataHgLSHSQSTMKVAVKMLKSTARSSEKqaLMSELKIMSHLGpHLNIVNLLGACT 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 427 EQAPICLVFEFMEHGCLSDYL----------------------------------------------------------- 447
Cdd:cd05107 112 KGGPIYIITEYCRYGDLVDYLhrnkhtflqyyldknrddgslisggstplsqrkshvslgsesdggymdmskdesadyvp 191
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 448 -------------------------------RTQRGLFAAET-------LLGMCLDVCEGMAYLEEACVIHRDLAARNCL 489
Cdd:cd05107 192 mqdmkgtvkyadiessnyespydqylpsapeRTRRDTLINESpalsymdLVGFSYQVANGMEFLASKNCVHRDLAARNVL 271
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 490 VGENQVIKVSDFGMTRFVL-DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPY-ENRSNSEV 567
Cdd:cd05107 272 ICEGKLVKICDFGLARDIMrDSNYISKGSTFLPLKWMAPESIFNNLYTTLSDVWSFGILLWEIFTLGGTPYpELPMNEQF 351
                       330       340       350       360
                ....*....|....*....|....*....|....*....|..
gi 15718680 568 VEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd05107 352 YNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQLV 393
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
358-615 6.08e-43

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: 155.59  E-value: 6.08e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWlNKDKVAIKTIREG-----AMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPIC 432
Cdd:cd14145   3 IDFSELVLEEIIGIGGFGKVYRAIW-IGDEVAVKAARHDpdediSQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLC 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEAC---VIHRDLAARNCLVGE--------NQVIKVSDF 501
Cdd:cd14145  82 LVMEFARGGPLNRVLSGKR--IPPDILVNWAVQIARGMNYLHCEAivpVIHRDLKSSNILILEkvengdlsNKILKITDF 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 502 GMTRFVLDDQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG-FRLYKP 580
Cdd:cd14145 160 GLAREWHRTTKMSAAGT---YAWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYGVAMNkLSLPIP 235
                       250       260       270
                ....*....|....*....|....*....|....*
gi 15718680 581 RLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14145 236 STCPEPFARLMEDCWNPDPHSRPPFTNILDQLTAI 270
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
365-613 8.66e-43

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: 155.11  E-value: 8.66e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWL---NKDKVAIKTIR--EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd14206   1 YLQEIGNGWFGKVILGEIFsdyTPAQVVVKELRvsAGPLEQRKFISEAQPYRSLQHPNILQCLGLCTETIPFLLIMEFCQ 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQR---GLFA------AETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR-FVLD 509
Cdd:cd14206  81 LGDLKRYLRAQRkadGMTPdlptrdLRTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSHnNYKE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGTKFPVKWASPEV-------FSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDI--STGFRLYKP 580
Cdd:cd14206 161 DYYLTPDRLWIPLRWVAPELldelhgnLIVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVvrEQQMKLAKP 240
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 15718680 581 RLASTHV---YQIMNHCWKErPEDRPAFSRLLRQLA 613
Cdd:cd14206 241 RLKLPYAdywYEIMQSCWLP-PSQRPSVEELHLQLS 275
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
369-616 1.24e-42

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: 153.42  E-value: 1.24e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGyWLNKDKVAIKTIREgamseedfIEEAEV--MMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDY 446
Cdd:cd14059   1 LGSGAQGAVFLG-KFRGEEVAVKKVRD--------EKETDIkhLRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQLYEV 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 447 LRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVLDDQYT--SSTGTkfpVKW 524
Cdd:cd14059  72 LRAGREI-TPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSK-ELSEKSTkmSFAGT---VAW 146
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 525 ASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI-STGFRLYKPRLASTHVYQIMNHCWKERPEDRP 603
Cdd:cd14059 147 MAPEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIIWGVgSNSLQLPVPSTCPDGFKLLMKQCWNSKPRNRP 225
                       250
                ....*....|...
gi 15718680 604 AFSRLLRQLaEIA 616
Cdd:cd14059 226 SFRQILMHL-DIA 237
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
367-612 1.95e-42

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: 153.90  E-value: 1.95e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYwLNKD----KVAIKTIREGAMSEED--FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd05042   1 QEIGNGWFGKVLLGE-IYSGtsvaQVVVKELKASANPKEQdtFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEFCDL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQR----GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM--TRFvLDDQYTS 514
Cdd:cd05042  80 GDLKAYLRSEReherGDSDTRTLQRMACEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLahSRY-KEDYIET 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 STGTKFPVKWASPEV-------FSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDI--STGFRLYKPRLAST 585
Cdd:cd05042 159 DDKLWFPLRWTAPELvtefhdrLLVVDQTKYSNIWSLGVTLWELFENGAQPYSNLSDLDVLAQVvrEQDTKLPKPQLELP 238
                       250       260       270
                ....*....|....*....|....*....|
gi 15718680 586 HV---YQIMNHCWKErPEDRPAFSRLLRQL 612
Cdd:cd05042 239 YSdrwYEVLQFCWLS-PEQRPAAEDVHLLL 267
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
369-615 2.07e-42

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: 154.04  E-value: 2.07e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDkVAIKTIREG-----AMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14146   2 IGVGGFGKVYRATWKGQE-VAVKAARQDpdediKATAESVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAE--------TLLGMCLDVCEGMAYL-EEACV--IHRDLAARNCLVGE--------NQVIKVSDFGMT 504
Cdd:cd14146  81 NRALAAANAAPGPRrarripphILVNWAVQIARGMLYLhEEAVVpiLHRDLKSSNILLLEkiehddicNKTLKITDFGLA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 505 RFVLDDQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG-FRLYKPRLA 583
Cdd:cd14146 161 REWHRTTKMSAAGT---YAWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGVAVNkLTLPIPSTC 236
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 584 STHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14146 237 PEPFAKLMKECWEQDPHIRPSFALILEQLTAI 268
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
366-611 2.43e-42

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: 153.51  E-value: 2.43e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd14014   5 VRLLGRGGMGEVYRARDTLLGRpVAIKVLRPELAEDEEFRErflrEARALARLSHPNIVRVYDVGEDDGRPYIVMEYVEG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKF 520
Cdd:cd14014  85 GSLADLLR-ERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSVLG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 PVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTG----FRLYKPRLASThVYQIMNHCWK 596
Cdd:cd14014 164 TPAYMAPEQARGGPVDPRSDIYSLGVVLYELL-TGRPPFDGDSPAAVLAKHLQEapppPSPLNPDVPPA-LDAIILRALA 241
                       250
                ....*....|....*....
gi 15718680 597 ERPEDRP----AFSRLLRQ 611
Cdd:cd14014 242 KDPEERPqsaaELLAALRA 260
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
369-615 7.14e-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: 7.14e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWlNKDKVAIKTIREG-----AMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14148   2 IGVGGFGKVYKGLW-RGEEVAVKAARQDpdediAVTAENVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGAL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRglFAAETLLGMCLDVCEGMAYLE-EACV--IHRDLAARNCLVGE--------NQVIKVSDFGMTRFVLDDQY 512
Cdd:cd14148  81 NRALAGKK--VPPHVLVNWAVQIARGMNYLHnEAIVpiIHRDLKSSNILILEpienddlsGKTLKITDFGLAREWHKTTK 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG-FRLYKPRLASTHVYQIM 591
Cdd:cd14148 159 MSAAGT---YAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAMNkLTLPIPSTCPEPFARLL 234
                       250       260
                ....*....|....*....|....
gi 15718680 592 NHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14148 235 EECWDPDPHGRPDFGSILKRLEDI 258
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
363-612 1.12e-41

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: 152.35  E-value: 1.12e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYW-----LNKDKVAIKTIRE-GAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQA--PICLV 434
Cdd:cd05081   6 LKYISQLGKGNFGSVELCRYdplgdNTGALVAVKQLQHsGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGrrSLRLV 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ--Y 512
Cdd:cd05081  86 MEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKdyY 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSegkipYENRSNS-------------------EVVEDIST 573
Cdd:cd05081 166 VVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFT-----YCDKSCSpsaeflrmmgcerdvpalcRLLELLEE 240
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 15718680 574 GFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05081 241 GQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSALGPQL 279
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
355-620 1.57e-41

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: 155.18  E-value: 1.57e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLG--YWLNKD----KVAIKTIREGAMSEED--FIEEAEVMMKL-SHPKLVQLYGVC 425
Cdd:cd05105  31 RWEFPRDGLVLGRILGSGAFGKVVEGtaYGLSRSqpvmKVAVKMLKPTARSSEKqaLMSELKIMTHLgPHLNIVNLLGAC 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LEQAPICLVFEFMEHGCLSDYLRTQRGLF-------------------AAET---------------------------- 458
Cdd:cd05105 111 TKSGPIYIITEYCFYGDLVNYLHKNRDNFlsrhpekpkkdldifginpADEStrsyvilsfenkgdymdmkqadttqyvp 190
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 459 ------------------------------------------------LLGMCLDVCEGMAYLEEACVIHRDLAARNCLV 490
Cdd:cd05105 191 mleikeaskysdiqrsnydrpasykgsndsevknllsddgseglttldLLSFTYQVARGMEFLASKNCVHRDLAARNVLL 270
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 491 GENQVIKVSDFGMTRFVL-DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENR-SNSEVV 568
Cdd:cd05105 271 AQGKIVKICDFGLARDIMhDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMiVDSTFY 350
                       330       340       350       360       370
                ....*....|....*....|....*....|....*....|....*....|..
gi 15718680 569 EDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFsrllRQLAEIAESGL 620
Cdd:cd05105 351 NKIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSF----LHLSDIVESLL 398
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
233-338 1.16e-39

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: 140.85  E-value: 1.16e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 233 NLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPcIKHYHIKEtNDNpKRYYVAEKYV 312
Cdd:cd10398   2 NLEIYEWYHKNITRNQAERLLRQESKEGAFIVRDSRHLGSYTISVFTRARRSTEAS-IKHYQIKK-NDS-GQWYVAERHL 78
                        90       100
                ....*....|....*....|....*.
gi 15718680 313 FDSIPLLINYHQHNGGGLVTRLRYPV 338
Cdd:cd10398  79 FQSIPELIQYHQHNAAGLMSRLRYPV 104
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
359-612 1.49e-39

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: 145.94  E-value: 1.49e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSELTFVQEIGSGQFGLVHLGYWlNKDKVAIKTIREG-----AMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICL 433
Cdd:cd14147   1 SFQELRLEEVIGIGGFGKVYRGSW-RGELVAVKAARQDpdediSVTAESVRQEARLFAMLAHPNIIALKAVCLEEPNLCL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLE-EAC--VIHRDLAARNCLVG--------ENQVIKVSDFG 502
Cdd:cd14147  80 VMEYAAGGPLSRALAGRR--VPPHVLVNWAVQIARGMHYLHcEALvpVIHRDLKSNNILLLqpienddmEHKTLKITDFG 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 503 MTRFVLDDQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG-FRLYKPR 581
Cdd:cd14147 158 LAREWHKTTQMSAAGT---YAWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAVNkLTLPIPS 233
                       250       260       270
                ....*....|....*....|....*....|.
gi 15718680 582 LASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd14147 234 TCPEPFAQLMADCWAQDPHRRPDFASILQQL 264
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
363-615 1.59e-39

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: 146.23  E-value: 1.59e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYWLNK-----DKVAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQA--PICL 433
Cdd:cd05079   6 LKRIRDLGEGHFGKVELCRYDPEgdntgEQVAVKSLKPESGGNHiaDLKKEIEILRNLYHENIVKYKGICTEDGgnGIKL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ-- 511
Cdd:cd05079  86 IMEFLPSGSLKEYLPRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKey 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSegkipYENRSNS-------------------EVVEDIS 572
Cdd:cd05079 166 YTVKDDLDSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLT-----YCDSESSpmtlflkmigpthgqmtvtRLVRVLE 240
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 15718680 573 TGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd05079 241 EGKRLPRPPNCPEEVYQLMRKCWEFQPSKRTTFQNLIEGFEAI 283
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
232-339 3.34e-39

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). 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. It is crucial for the function of Tec PH domains and it's lack of presence in Txk 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. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 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: 198260 [Multi-domain]  Cd Length: 106  Bit Score: 139.20  E-value: 3.34e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 232 NNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPCiKHYHIKETNDNpkRYYVAEKY 311
Cdd:cd10397   1 DSLEMYEWYSKNMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSAGDPQGVI-RHYVVCSTPQS--QYYLAEKH 77
                        90       100
                ....*....|....*....|....*...
gi 15718680 312 VFDSIPLLINYHQHNGGGLVTRLRYPVC 339
Cdd:cd10397  78 LFSTIPELINYHQHNAAGLISRLKYPVS 105
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
370-612 7.52e-39

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: 143.17  E-value: 7.52e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 370 GSGQFGLVHLGYWLNKDK-VAIKTIREgamseedfIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYL 447
Cdd:cd14060   2 GGGSFGSVYRAIWVSQDKeVAVKKLLK--------IEkEAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSLFDYL 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 448 RTQRG-LFAAETLLGMCLDVCEGMAYL-EEA--CVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTkFPvk 523
Cdd:cd14060  74 NSNESeEMDMDQIMTWATDIAKGMHYLhMEApvKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSLVGT-FP-- 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 524 WASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSE----VVEDistGFRLYKPRLASTHVYQIMNHCWKERP 599
Cdd:cd14060 151 WMAPEVIQSLPVSETCDTYSYGVVLWEMLTR-EVPFKGLEGLQvawlVVEK---NERPTIPSSCPRSFAELMRRCWEADV 226
                       250
                ....*....|...
gi 15718680 600 EDRPAFSRLLRQL 612
Cdd:cd14060 227 KERPSFKQIIGIL 239
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
362-610 1.07e-38

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: 143.11  E-value: 1.07e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd05122   1 LFEILEKIGKGGFGVVYKARHKKTGQiVAIKKINlESKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS-TGT 518
Cdd:cd05122  81 GGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTRNTfVGT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 KFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTG--FRLYKPRLASTHVYQIMNHCWK 596
Cdd:cd05122 161 PY---WMAPEVIQGKPYGFKADIWSLGITAIEMA-EGKPPYSELPPMKALFLIATNgpPGLRNPKKWSKEFKDFLKKCLQ 236
                       250
                ....*....|....
gi 15718680 597 ERPEDRPAFSRLLR 610
Cdd:cd05122 237 KDPEKRPTAEQLLK 250
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
355-608 1.33e-38

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: 146.53  E-value: 1.33e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLV--HLGYWLNKD----KVAIKTIREGAMSEED--FIEEAEVMMKLSHPK-LVQLYGVC 425
Cdd:cd05106  32 KWEFPRDNLQFGKTLGAGAFGKVveATAFGLGKEdnvlRVAVKMLKASAHTDEReaLMSELKILSHLGQHKnIVNLLGAC 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LEQAPICLVFEFMEHGCLSDYLRTQrglfaAETLLGM---------------------------------CLD------- 465
Cdd:cd05106 112 THGGPVLVITEYCCYGDLLNFLRKK-----AETFLNFvmalpeisetssdyknitlekkyirsdsgfssqGSDtyvemrp 186
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 466 ----------------------------------VCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD- 510
Cdd:cd05106 187 vsssssqssdskdeedtedswpldlddllrfssqVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARDIMNDs 266
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 QYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRS-NSEVVEDISTGFRLYKPRLASTHVYQ 589
Cdd:cd05106 267 NYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILvNSKFYKMVKRGYQMSRPDFAPPEIYS 346
                       330
                ....*....|....*....
gi 15718680 590 IMNHCWKERPEDRPAFSRL 608
Cdd:cd05106 347 IMKMCWNLEPTERPTFSQI 365
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
369-610 1.97e-38

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: 142.66  E-value: 1.97e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGywLNKD---KVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd06606   8 LGKGSFGSVYLA--LNLDtgeLMAVKEVELSGDSEEEleaLEREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGGS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGLfaAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST----G 517
Cdd:cd06606  86 LASLLKKFGKL--PEPVVRKYTrQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIATGEGTkslrG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSN--SEVVEDISTGFRLYKPRLASTHVYQIMNHCW 595
Cdd:cd06606 164 TPY---WMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPWSELGNpvAALFKIGSSGEPPPIPEHLSEEAKDFLRKCL 239
                       250
                ....*....|....*
gi 15718680 596 KERPEDRPAFSRLLR 610
Cdd:cd06606 240 QRDPKKRPTADELLQ 254
SH3_ITK cd11908
Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) ...
174-229 3.47e-38

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212841 [Multi-domain]  Cd Length: 56  Bit Score: 134.76  E-value: 3.47e-38
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 174 TVVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEK 229
Cdd:cd11908   1 TLVIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRVQDKNGHEGYVPSSYLVEK 56
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
365-603 5.29e-38

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: 141.66  E-value: 5.29e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLG---YWLNKDKVAIKTIREGAMSEED--FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd05087   1 YLKEIGHGWFGKVFLGevnSGLSSTQVVVKELKASASVQDQmqFLEEAQPYRALQHTNLLQCLAQCAEVTPYLLVMEFCP 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRglfAAE-------TLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL-DDQ 511
Cdd:cd05087  81 LGDLKGYLRSCR---AAEsmapdplTLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCKYkEDY 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFPVKWASPEVFS-------FSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDI--STGFRLYKPRL 582
Cdd:cd05087 158 FVTADQLWVPLRWIAPELVDevhgnllVVDQTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLTYTvrEQQLKLPKPQL 237
                       250       260
                ....*....|....*....|....
gi 15718680 583 A---STHVYQIMNHCWKErPEDRP 603
Cdd:cd05087 238 KlslAERWYEVMQFCWLQ-PEQRP 260
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
354-614 6.71e-38

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 146.70  E-value: 6.71e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 354 GKWVIdpseltfVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQ 428
Cdd:COG0515   7 GRYRI-------LRLLGRGGMGVVYLARDLRLGRpVALKVLRPELAADPEARErfrrEARALARLNHPNIVRVYDVGEED 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 429 APICLVFEFMEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL 508
Cdd:COG0515  80 GRPYLVMEYVEGESLADLLR-RRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALG 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG----FRLYKPRLaS 584
Cdd:COG0515 159 GATLTQTGTVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREppppPSELRPDL-P 236
                       250       260       270
                ....*....|....*....|....*....|....
gi 15718680 585 THVYQIMNHCWKERPEDRP----AFSRLLRQLAE 614
Cdd:COG0515 237 PALDAIVLRALAKDPEERYqsaaELAAALRAVLR 270
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
365-612 1.17e-37

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: 140.77  E-value: 1.17e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDKVAIKTIRE-----GAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd05086   1 YIQEIGNGWFGKVLLGEIYTGTSVARVVVKElkasaNPKEQDDFLQQGEPYYILQHPNILQCVGQCVEAIPYLLVFEFCD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGLFAAET----LLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd05086  81 LGDLKTYLANQQEKLRGDSqimlLQRMACEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGFSRYKEDYIET 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 TGTKF-PVKWASPE-VFSF------SRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDI--STGFRLYKPRLA-- 583
Cdd:cd05086 161 DDKKYaPLRWTAPElVTSFqdgllaAEQTKYSNIWSLGVTLWELFENAAQPYSDLSDREVLNHVikERQVKLFKPHLEqp 240
                       250       260       270
                ....*....|....*....|....*....|
gi 15718680 584 -STHVYQIMNHCWKErPEDRPAFSRLLRQL 612
Cdd:cd05086 241 ySDRWYEVLQFCWLS-PEKRPTAEEVHRLL 269
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
369-614 2.87e-37

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: 139.20  E-value: 2.87e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKdKVAIKTIRE---GAMSEED-FIEEAEVMMKLSHPKLVQLYGVCLEQ-APICLVFEFMEHGCL 443
Cdd:cd14064   1 IGSGSFGKVYKGRCRNK-IVAIKRYRAntyCSKSDVDmFCREVSILCRLNHPCVIQFVGACLDDpSQFAIVTQYVSGGSL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEAC--VIHRDLAARNCLVGENQVIKVSDFGMTRFVL---DDQYTSSTGT 518
Cdd:cd14064  80 FSLLHEQKRVIDLQSKLIIAVDVAKGMEYLHNLTqpIIHRDLNSHNILLYEDGHAVVADFGESRFLQsldEDNMTKQPGN 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 kfpVKWASPEVFSFS-RYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDIStgFRLYKPRLAST---HVYQIMNHC 594
Cdd:cd14064 160 ---LRWMAPEVFTQCtRYSIKADVFSYALCLWELLT-GEIPFAHLKPAAAAADMA--YHHIRPPIGYSipkPISSLLMRG 233
                       250       260
                ....*....|....*....|
gi 15718680 595 WKERPEDRPAFSRLLRQLAE 614
Cdd:cd14064 234 WNAEPESRPSFVEIVALLEP 253
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
369-615 7.12e-37

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: 138.56  E-value: 7.12e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTIREGAM--SEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDY 446
Cdd:cd14066   1 IGSGGFGTVYKGVLENGTVVAVKRLNEMNCaaSKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDR 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 447 LRTQRGLFAA--ETLLGMCLDVCEGMAYLEEAC---VIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGtkfP 521
Cdd:cd14066  81 LHCHKGSPPLpwPQRLKIAKGIARGLEYLHEECpppIIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVSKTS---A 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 522 VKWAS----PEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIP-YENRSN-------SEVVEDISTGFR-LYKPRLASTHV- 587
Cdd:cd14066 158 VKGTIgylaPEYIRTGRVSTKSDVYSFGVVLLELLT-GKPAvDENRENasrkdlvEWVESKGKEELEdILDKRLVDDDGv 236
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 15718680 588 --------YQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14066 237 eeeevealLRLALLCTRSDPSLRPSMKEVVQMLEKL 272
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
363-617 4.29e-36

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: 136.95  E-value: 4.29e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHL-GYWLNKDK----VAIKTIRE--GAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP--ICL 433
Cdd:cd05080   6 LKKIRDLGEGHFGKVSLyCYDPTNDGtgemVAVKALKAdcGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEQGGksLQL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYL-RTQRGLfaaETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ- 511
Cdd:cd05080  86 IMEYVPLGSLRDYLpKHSIGL---AQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHe 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 -YTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEV-------------FSEGKIPYENRSNS-EVVEDISTGFR 576
Cdd:cd05080 163 yYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELlthcdssqspptkFLEMIGIAQGQMTVvRLIELLERGER 242
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 15718680 577 LYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAE 617
Cdd:cd05080 243 LPCPDKCPQEVYHLMKNCWETEASFRPTFENLIPILKTVHE 283
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
369-605 6.42e-36

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: 135.66  E-value: 6.42e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGY---WlnKDKVAIKTIREGAMSEE---DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd13978   1 LGSGGFGTVSKARhvsW--FGMVAIKCLHSSPNCIEerkALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENGS 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEAC--VIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKF 520
Cdd:cd13978  79 LKSLLEREIQDVPWSLRFRIIHEIALGMNFLHNMDppLLHHDLKPENILLDNHFHVKISDFGLSKLGMKSISANRRRGTE 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 P----VKWASPEVFS--FSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI-STGFR-------LYKPRLASTH 586
Cdd:cd13978 159 NlggtPIYMAPEAFDdfNKKPTSKSDVYSFAIVIWAVLT-RKEPFENAINPLLIMQIvSKGDRpslddigRLKQIENVQE 237
                       250
                ....*....|....*....
gi 15718680 587 VYQIMNHCWKERPEDRPAF 605
Cdd:cd13978 238 LISLMIRCWDGNPDARPTF 256
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
233-338 1.39e-35

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, 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. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. 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: 198262  Cd Length: 106  Bit Score: 129.30  E-value: 1.39e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 233 NLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNpCIKHYHIKETNDNpkRYYVAEKYV 312
Cdd:cd10399   2 NLDAYDWFAGNISRSQSEQLLRQKGKEGAFMVRNSSQVGMYTVSLFSKAVNDKKG-TVKHYHVHTNAEN--KLYLAENYC 78
                        90       100
                ....*....|....*....|....*.
gi 15718680 313 FDSIPLLINYHQHNGGGLVTRLRYPV 338
Cdd:cd10399  79 FDSIPKLIHYHQHNSAGMITRLRHPV 104
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
355-614 3.48e-35

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: 136.57  E-value: 3.48e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLV--HLGYWLNKD----KVAIKTIREGAMS--EEDFIEEAEVMMKL-SHPKLVQLYGVC 425
Cdd:cd05104  29 KWEFPRDRLRFGKTLGAGAFGKVveATAYGLAKAdsamTVAVKMLKPSAHSteREALMSELKVLSYLgNHINIVNLLGAC 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 426 LEQAPICLVFEFMEHGCLSDYLRTQRGLFA-------------------------------------------------- 455
Cdd:cd05104 109 TVGGPTLVITEYCCYGDLLNFLRRKRDSFIcpkfedlaeaalyrnllhqremacdslneymdmkpsvsyvvptkadkrrg 188
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 456 ------------------------AETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD- 510
Cdd:cd05104 189 vrsgsyvdqdvtseileedelaldTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIRNDs 268
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 QYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRS-NSEVVEDISTGFRLYKPRLASTHVYQ 589
Cdd:cd05104 269 NYVVKGNARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPvDSKFYKMIKEGYRMDSPEFAPSEMYD 348
                       330       340
                ....*....|....*....|....*
gi 15718680 590 IMNHCWKERPEDRPAFSRLLRQLAE 614
Cdd:cd05104 349 IMRSCWDADPLKRPTFKQIVQLIEQ 373
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
368-610 6.52e-33

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: 126.96  E-value: 6.52e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGywLNKDK---VAIKTIREGAMSEEDFIE---EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd06627   7 LIGRGAFGSVYKG--LNLNTgefVAIKQISLEKIPKSDLKSvmgEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRtQRGLFAaETLLGMCLD-VCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG----MTRfvLDDQYTSST 516
Cdd:cd06627  85 SLASIIK-KFGKFP-ESLVAVYIYqVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGvatkLNE--VEKDENSVV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNS----EVVEDISTGFrlykPRLASTHVYQIMN 592
Cdd:cd06627 161 GTPY---WMAPEVIEMSGVTTASDIWSVGCTVIELL-TGNPPYYDLQPMaalfRIVQDDHPPL----PENISPELRDFLL 232
                       250
                ....*....|....*...
gi 15718680 593 HCWKERPEDRPAFSRLLR 610
Cdd:cd06627 233 QCFQKDPTLRPSAKELLK 250
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
364-595 3.31e-32

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: 124.94  E-value: 3.31e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYW-LNKDKVAIKTIREGAMSEEDFI---EEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd14003   3 ELGKTLGEGSFGKVKLARHkLTGEKVAIKIIDKSKLKEEIEEkikREIEIMKLLNHPNIIKLYEVIETENKIYLVMEYAS 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGL--FAAETLLGMcldVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST- 516
Cdd:cd14003  83 GGELFDYIVNNGRLseDEARRFFQQ---LISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGGSLLKTFc 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 GTKFpvkWASPEVFSFSRY-SSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfRLYKPRLAST---------- 585
Cdd:cd14003 160 GTPA---YAAPEVLLGRKYdGPKADVWSLGVILYAMLT-GYLPFDDDNDSKLFRKILKG-KYPIPSHLSPdardlirrml 234
                       250
                ....*....|....*...
gi 15718680 586 --------HVYQIMNHCW 595
Cdd:cd14003 235 vvdpskriTIEEILNHPW 252
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
363-612 4.17e-31

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: 122.20  E-value: 4.17e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLG-------YWLNKDKVAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPIcLV 434
Cdd:cd05037   1 ITFHEHLGQGTFTNIYDGilrevgdGRVQEVEVLLKVLDsDHRDISESFFETASLMSQISHKHLVKLYGVCVADENI-MV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV------GENQVIKVSDFGMTRFVL 508
Cdd:cd05037  80 QEYVRYGPLDKYLRRMGNNVPLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNILLaregldGYPPFIKLSDPGVPITVL 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSStgtkfPVKWASPEVF--SFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLykPRLASTH 586
Cdd:cd05037 160 SREERVD-----RIPWIAPECLrnLQANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQL--PAPDCAE 232
                       250       260
                ....*....|....*....|....*.
gi 15718680 587 VYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05037 233 LAELIMQCWTYEPTKRPSFRAILRDL 258
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
364-574 7.44e-31

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: 121.43  E-value: 7.44e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYWLN-KDKVAIKTI---REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd05117   3 ELGKVLGRGSFGVVRLAVHKKtGEEYAVKIIdkkKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMELCT 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLrTQRGLF----AAEtllgMCLDVCEGMAYLEEACVIHRDLAARNCLV---GENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd05117  83 GGELFDRI-VKKGSFsereAAK----IMKQILSAVAYLHSQGIVHRDLKPENILLaskDPDSPIKIIDFGLAKIFEEGEK 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 513 TSST-GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd05117 158 LKTVcGTPY---YVAPEVLKGKGYGKKCDIWSLGVILYILLC-GYPPFYGETEQELFEKILKG 216
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
371-606 2.74e-30

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: 119.91  E-value: 2.74e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 371 SGQFGLVHLGYWLNKDKVAIKTIREGAMS---EEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYL 447
Cdd:cd14027   3 SGGFGKVSLCFHRTQGLVVLKTVYTGPNCiehNEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 448 RtqrglfAAETLLGM----CLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF---------------VL 508
Cdd:cd14027  83 K------KVSVPLSVkgriILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFkmwskltkeehneqrEV 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTKFpvkWASPEVFS--FSRYSSKSDVWSFGVLMWEVFSeGKIPYEN-RSNSEVVEDISTGFRlykPRLAS- 584
Cdd:cd14027 157 DGTAKKNAGTLY---YMAPEHLNdvNAKPTEKSDVYSFAIVLWAIFA-NKEPYENaINEDQIIMCIKSGNR---PDVDDi 229
                       250       260
                ....*....|....*....|....*..
gi 15718680 585 -----THVYQIMNHCWKERPEDRPAFS 606
Cdd:cd14027 230 teycpREIIDLMKLCWEANPEARPTFP 256
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
366-611 6.16e-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: 118.72  E-value: 6.16e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVhlgyWLNKDK-----VAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd08215   5 IRVIGKGSFGSA----YLVRRKsdgklYVLKEIDLSNMSEkerEEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQR---GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVLD---DQ 511
Cdd:cd08215  81 ADGGDLAQKIKKQKkkgQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISK-VLEsttDL 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfrLYK--PRLASTHVYQ 589
Cdd:cd08215 160 AKTVVGTPY---YLSPELCENKPYNYKSDIWALGCVLYELCT-LKHPFEANNLPALVYKIVKG--QYPpiPSQYSSELRD 233
                       250       260
                ....*....|....*....|..
gi 15718680 590 IMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd08215 234 LVNSMLQKDPEKRPSANEILSS 255
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
369-617 1.58e-29

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: 117.62  E-value: 1.58e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLR 448
Cdd:cd14156   1 IGSGFFSKVYKVTHGATGKVMVVKIYKNDVDQHKIVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLEELLA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 449 TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIK---VSDFGMTRFVLD------DQYTSSTGTK 519
Cdd:cd14156  81 REELPLSWREKVELACDISRGMVYLHSKNIYHRDLNSKNCLIRVTPRGReavVTDFGLAREVGEmpandpERKLSLVGSA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 520 FpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFseGKIPyenrSNSEVV---EDISTGFRLYKPRLAST--HVYQIMNHC 594
Cdd:cd14156 161 F---WMAPEMLRGEPYDRKVDVFSFGIVLCEIL--ARIP----ADPEVLprtGDFGLDVQAFKEMVPGCpePFLDLAASC 231
                       250       260
                ....*....|....*....|...
gi 15718680 595 WKERPEDRPAFSRLLRQLAEIAE 617
Cdd:cd14156 232 CRMDAFKRPSFAELLDELEDIAE 254
Pkinase pfam00069
Protein kinase domain;
363-610 1.63e-29

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 116.19  E-value: 1.63e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   363 LTFVQEIGSGQFGLVHLGY-WLNKDKVAIKTI---REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFM 438
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKhRDTGKIVAIKKIkkeKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   439 EHGCLSDYLRTQRGL-------FAAETLLGMcldvcegmayleeacvihrdlaarnclvgENQVikvsdfgmtrfvlddQ 511
Cdd:pfam00069  81 EGGSLFDLLSEKGAFsereakfIMKQILEGL-----------------------------ESGS---------------S 116
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   512 YTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI--STGFRLYKPRLASTHVYQ 589
Cdd:pfam00069 117 LTTFVGTPW---YMAPEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPGINGNEIYELIidQPYAFPELPSNLSEEAKD 192
                         250       260
                  ....*....|....*....|.
gi 15718680   590 IMNHCWKERPEDRPAFSRLLR 610
Cdd:pfam00069 193 LLKKLLKKDPSKRLTATQALQ 213
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
356-618 4.84e-29

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: 116.70  E-value: 4.84e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWlnKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVClEQAPIC 432
Cdd:cd14151   3 WEIPDGQITVGQRIGSGSFGTVYKGKW--HGDVAVKMLNVTAPTPQQlqaFKNEVGVLRKTRHVNILLFMGYS-TKPQLA 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM----TRFVL 508
Cdd:cd14151  80 IVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLatvkSRWSG 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTkfpVKWASPEVFSF---SRYSSKSDVWSFGVLMWEVFSeGKIPYENRSN-SEVVEDISTGFrlYKPRLAS 584
Cdd:cd14151 160 SHQFEQLSGS---ILWMAPEVIRMqdkNPYSFQSDVYAFGIVLYELMT-GQLPYSNINNrDQIIFMVGRGY--LSPDLSK 233
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 15718680 585 TH------VYQIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd14151 234 VRsncpkaMKRLMAECLKKKRDERPLFPQILASIELLARS 273
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
388-615 1.74e-28

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: 114.79  E-value: 1.74e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 388 VAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVC 467
Cdd:cd13992  28 VAIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNREIKMDWMFKSSFIKDIV 107
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 468 EGMAYLEEACVI-HRDLAARNCLVGENQVIKVSDFGMTRFVLD--DQYTSSTGTKFPVKWASPEVFSFS----RYSSKSD 540
Cdd:cd13992 108 KGMNYLHSSSIGyHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEqtNHQLDEDAQHKKLLWTAPELLRGSllevRGTQKGD 187
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 541 VWSFGVLMWEVFsEGKIPYENRSNSEVVED-ISTGFRLYKPRLASTH------VYQIMNHCWKERPEDRPAFSRLLRQLA 613
Cdd:cd13992 188 VYSFAIILYEIL-FRSDPFALEREVAIVEKvISGGNKPFRPELAVLLdefpprLVLLVKQCWAENPEKRPSFKQIKKTLT 266

                ..
gi 15718680 614 EI 615
Cdd:cd13992 267 EN 268
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
365-574 2.14e-28

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: 114.11  E-value: 2.14e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGywlnKDK-----VAIK-----TIREGAMsEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd14007   4 IGKPLGKGKFGNVYLA----REKksgfiVALKvisksQLQKSGL-EHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLI 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd14007  79 LEYAPNGELYKELKKQ-KRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSVHAPSNRRKT 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 STGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd14007 158 FCGT---LDYLPPEMVEGKEYDYKVDIWSLGVLCYE-LLVGKPPFESKSHQETYKRIQNV 213
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
362-612 2.21e-28

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: 114.75  E-value: 2.21e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWlnKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFM 438
Cdd:cd14063   1 ELEIKEVIGKGRFGRVHRGRW--HGDVAIKLLNIDYLNEEQleaFKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVTSLC 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIkVSDFGMTRFVLDDQYTSSTGT 518
Cdd:cd14063  79 KGRTLYSLIHERKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLENGRVV-ITDFGLFSLSGLLQPGRREDT 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 -KFPVKWA---SPEV----------FSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFrlyKPRLAS 584
Cdd:cd14063 158 lVIPNGWLcylAPEIiralspdldfEESLPFTKASDVYAFGTVWYELLA-GRWPFKEQPAESIIWQVGCGK---KQSLSQ 233
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 585 TH----VYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd14063 234 LDigreVKDILMQCWAYDPEKRPTFSDLLRML 265
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
363-610 2.31e-28

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: 114.23  E-value: 2.31e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYWLNK-DKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd06614   2 YKNLEKIGEGASGEVYKATDRATgKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDGG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLrTQRGLFAAETLLG-MCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG----MTRFVldDQYTSST 516
Cdd:cd06614  82 SLTDII-TQNPVRMNESQIAyVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGfaaqLTKEK--SKRNSVV 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGF--RLYKPRLASTHVYQIMNHC 594
Cdd:cd06614 159 GTPY---WMAPEVIKRKDYGPKVDIWSLGIMCIEM-AEGEPPYLEEPPLRALFLITTKGipPLKNPEKWSPEFKDFLNKC 234
                       250
                ....*....|....*.
gi 15718680 595 WKERPEDRPAFSRLLR 610
Cdd:cd06614 235 LVKDPEKRPSAEELLQ 250
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
369-571 2.78e-28

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: 114.19  E-value: 2.78e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLN-KDKVAIKTI--------REGAMS-------EEDFIEEAEVMMKLSHPKLVQLYGVC--LEQAP 430
Cdd:cd14008   1 LGRGSFGKVKLALDTEtGQLYAIKIFnksrlrkrREGKNDrgkiknaLDDVRREIAIMKKLDHPNIVRLYEVIddPESDK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGCLSDYLRTQRGL-FAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL- 508
Cdd:cd14008  81 LYLVLEYCEGGPVMELDSGDRVPpLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFEd 160
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 509 -DDQYTSSTGTkfPVkWASPEVFSFSR--YSSK-SDVWSFGVLMWeVFSEGKIPYENRSNSEVVEDI 571
Cdd:cd14008 161 gNDTLQKTAGT--PA-FLAPELCDGDSktYSGKaADIWALGVTLY-CLVFGRLPFNGDNILELYEAI 223
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
393-608 4.17e-28

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: 113.89  E-value: 4.17e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 393 IREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGlFAAETLLGMCLDVCEGMAY 472
Cdd:cd14222  27 IRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDFLRADDP-FPWQQKVSFAKGIASGMAY 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 473 LEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTgTKFPVK--------------------WASPEVFSF 532
Cdd:cd14222 106 LHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRLIVEEKKKPPP-DKPTTKkrtlrkndrkkrytvvgnpyWMAPEMLNG 184
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 533 SRYSSKSDVWSFGVLMWEVFseGKIpYENRSNSEVVEDISTGFRLYKPRLASTHV----YQIMNHCWKERPEDRPAFSRL 608
Cdd:cd14222 185 KSYDEKVDIFSFGIVLCEII--GQV-YADPDCLPRTLDFGLNVRLFWEKFVPKDCppafFPLAAICCRLEPDSRPAFSKL 261
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
369-612 6.09e-28

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: 112.87  E-value: 6.09e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKdkVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQApICLVFEFMEHGCLSD 445
Cdd:cd14062   1 IGSGSFGTVYKGRWHGD--VAVKKLNVTDPTPSQlqaFKNEVAVLRKTRHVNILLFMGYMTKPQ-LAIVTQWCEGSSLYK 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM----TRFVLDDQYTSSTGTkfp 521
Cdd:cd14062  78 HLHVLETKFEMLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLatvkTRWSGSQQFEQPTGS--- 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 522 VKWASPEVFSF---SRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEdISTGFRLYKPRLAS------THVYQIMN 592
Cdd:cd14062 155 ILWMAPEVIRMqdeNPYSFQSDVYAFGIVLYELLT-GQLPYSHINNRDQIL-FMVGRGYLRPDLSKvrsdtpKALRRLME 232
                       250       260
                ....*....|....*....|
gi 15718680 593 HCWKERPEDRPAFSRLLRQL 612
Cdd:cd14062 233 DCIKFQRDERPLFPQILASL 252
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
366-610 1.02e-27

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: 112.52  E-value: 1.02e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVhlgyWLNKDKVA--------IKTIREGAMSEEDFIE---EAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd08222   5 VRKLGSGNFGTV----YLVSDLKAtadeelkvLKEISVGELQPDETVDanrEAKLLSKLDHPAIVKFHDSFVEKESFCIV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQR---GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVgENQVIKVSDFGMTRFVL--D 509
Cdd:cd08222  81 TEYCEGGDLDDKISEYKksgTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFL-KNNVIKVGDFGISRILMgtS 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQ 589
Cdd:cd08222 160 DLATTFTGTPY---YMSPEVLKHEGYNSKSDIWSLGCILYEMCCL-KHAFDGQNLLSVMYKIVEGETPSLPDKYSKELNA 235
                       250       260
                ....*....|....*....|.
gi 15718680 590 IMNHCWKERPEDRPAFSRLLR 610
Cdd:cd08222 236 IYSRMLNKDPALRPSAAEILK 256
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
364-595 1.14e-26

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: 109.58  E-value: 1.14e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYW---LNKDKVAIKTIREgAMSEEDFIE-----EAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd14080   3 RLGKTIGEGSYSKVKLAEYtksGLKEKVACKIIDK-KKAPKDFLEkflprELEILRKLRHPNIIQVYSIFERGSKVFIFM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRGLFAAETLLgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY--T 513
Cdd:cd14080  82 EYAEHGDLLEYIQKRGALSESQARI-WFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLCPDDDGdvL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SST--GTKFpvkWASPEVFSFSRYSSK-SDVWSFGVLMWeVFSEGKIPYENRSNSEVVED-ISTGFRLYKPRL------- 582
Cdd:cd14080 161 SKTfcGSAA---YAAPEILQGIPYDPKkYDIWSLGVILY-IMLCGSMPFDDSNIKKMLKDqQNRKVRFPSSVKklspeck 236
                       250       260
                ....*....|....*....|....*
gi 15718680 583 ------------ASTHVYQIMNHCW 595
Cdd:cd14080 237 dlidqllepdptKRATIEEILNHPW 261
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
369-612 2.69e-26

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: 107.96  E-value: 2.69e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLR 448
Cdd:cd14065   1 LGKGFFGEVYKVTHRETGKVMVMKELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGTLEELLK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 449 TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGE---NQVIKVSDFGMTRFVLDDQYT--------SSTG 517
Cdd:cd14065  81 SMDEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREanrGRNAVVADFGLAREMPDEKTKkpdrkkrlTVVG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFseGKIPyenrSNSEVV---EDIS---TGFRLYKPRLASTHVYQIM 591
Cdd:cd14065 161 SPY---WMAPEMLRGESYDEKVDVFSFGIVLCEII--GRVP----ADPDYLprtMDFGldvRAFRTLYVPDCPPSFLPLA 231
                       250       260
                ....*....|....*....|.
gi 15718680 592 NHCWKERPEDRPAFSRLLRQL 612
Cdd:cd14065 232 IRCCQLDPEKRPSFVELEHHL 252
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
393-608 3.30e-26

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: 108.36  E-value: 3.30e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 393 IREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAY 472
Cdd:cd14154  27 IRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGGTLKDVLKDMARPLPWAQRVRFAKDIASGMAY 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 473 LEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ----YTSSTGTKFPVK---------------WASPEVFSFS 533
Cdd:cd14154 107 LHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLIVEERlpsgNMSPSETLRHLKspdrkkrytvvgnpyWMAPEMLNGR 186
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 534 RYSSKSDVWSFGVLMWEVFS--EGKIPYENRSnsevvEDISTGFRLYKPRLAST---HVYQIMNHCWKERPEDRPAFSRL 608
Cdd:cd14154 187 SYDEKVDIFSFGIVLCEIIGrvEADPDYLPRT-----KDFGLNVDSFREKFCAGcppPFFKLAFLCCDLDPEKRPPFETL 261
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
368-611 7.68e-26

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: 106.73  E-value: 7.68e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVH-LGYWLNKDKVAIKTIREGAMS---EEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd08529   7 KLGKGSFGVVYkVVRKVDGRVYALKQIDISRMSrkmREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYAENGDL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVLDDQYT-SST--GTK 519
Cdd:cd08529  87 HSLIKSQRGrPLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAK-ILSDTTNfAQTivGTP 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 520 FpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERP 599
Cdd:cd08529 166 Y---YLSPELCEDKPYNEKSDVWALGCVLYELCT-GKHPFEAQNQGALILKIVRGKYPPISASYSQDLSQLIDSCLTKDY 241
                       250
                ....*....|..
gi 15718680 600 EDRPAFSRLLRQ 611
Cdd:cd08529 242 RQRPDTTELLRN 253
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
369-615 9.34e-26

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: 107.20  E-value: 9.34e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTI-REG-AMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDY 446
Cdd:cd14664   1 IGRGGAGTVYKGVMPNGTLVAVKRLkGEGtQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGEL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 447 LRTQ---RGLFAAETLLGMCLDVCEGMAYLEEAC---VIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKF 520
Cdd:cd14664  81 LHSRpesQPPLDWETRQRIALGSARGLAYLHHDCsplIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMSSVAG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 PVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVeDISTGFR----------LYKPRLAST----- 585
Cdd:cd14664 161 SYGYIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRPFDEAFLDDGV-DIVDWVRglleekkveaLVDPDLQGVyklee 238
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 586 --HVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14664 239 veQVFQVALLCTQSSPMERPTMREVVRMLEGD 270
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
361-610 1.79e-25

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: 106.14  E-value: 1.79e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLG-YWLNKDKVAIKTIREGamSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd06623   1 SDLERVKVLGQGSSGVVYKVrHKPTGKIYALKKIHVD--GDEEFRKqllrELKTLRSCESPYVVKCYGAFYKEGEISIVL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYL-EEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD--DQY 512
Cdd:cd06623  79 EYMDGGSLADLLK-KVGKIPEPVLAYIARQILKGLDYLhTKRHIIHRDIKPSNLLINSKGEVKIADFGISKVLENtlDQC 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPYENRSNSEVVE--DISTGFRLYKPR--LASTHVY 588
Cdd:cd06623 158 NTFVGT---VTYMSPERIQGESYSYAADIWSLGLTLLE-CALGKFPFLPPGQPSFFElmQAICDGPPPSLPaeEFSPEFR 233
                       250       260
                ....*....|....*....|..
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd06623 234 DFISACLQKDPKKRPSAAELLQ 255
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
367-610 2.18e-25

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: 105.61  E-value: 2.18e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGY-WLNKDKVAIKTIR-EGAMSEE---DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFmehg 441
Cdd:cd06607   7 REIGHGSFGAVYYARnKRTSEVVAIKKMSySGKQSTEkwqDIIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVMEY---- 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CL---SDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVldDQYTSSTGT 518
Cdd:cd06607  83 CLgsaSDIVEVHKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLV--CPANSFVGT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 KFpvkWASPEV---FSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGfrlYKPRLASTH----VYQIM 591
Cdd:cd06607 161 PY---WMAPEVilaMDEGQYDGKVDVWSLGITCIEL-AERKPPLFNMNAMSALYHIAQN---DSPTLSSGEwsddFRNFV 233
                       250
                ....*....|....*....
gi 15718680 592 NHCWKERPEDRPAFSRLLR 610
Cdd:cd06607 234 DSCLQKIPQDRPSAEDLLK 252
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
369-615 3.37e-25

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: 106.04  E-value: 3.37e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYwLNKDKVAIKTIRE--GAMSEE---DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14158  23 LGEGGFGVVFKGY-INDKNVAVKKLAAmvDISTEDltkQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVYTYMPNGSL 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTqrglfAAETL---LGMCLDVCEGMA----YLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR----FVLDDQY 512
Cdd:cd14158 102 LDRLAC-----LNDTPplsWHMRCKIAQGTAnginYLHENNHIHRDIKSANILLDETFVPKISDFGLARasekFSQTIMT 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTkfpVKWASPEVFSfSRYSSKSDVWSFGVLMWEVFSeGKIPY-ENRSNS------EVVEDISTGFRLYKPRLAST 585
Cdd:cd14158 177 ERIVGT---TAYMAPEALR-GEITPKSDIFSFGVVLLEIIT-GLPPVdENRDPQllldikEEIEDEEKTIEDYVDKKMGD 251
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 15718680 586 -------HVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14158 252 wdstsieAMYSVASQCLNDKKNRRPDIAKVQQLLQEL 288
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
369-611 3.69e-25

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: 104.78  E-value: 3.69e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd08530   8 LGKGSYGSVYKVKRLSDNQVyALKEVNLGSLSQkerEDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYAPFGDLS 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYL---RTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVLDDQYT-SSTGTKF 520
Cdd:cd08530  88 KLIskrKKKRRLFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISK-VLKKNLAkTQIGTPL 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 pvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPE 600
Cdd:cd08530 167 ---YAAPEVWKGRPYDYKSDIWSLGCLLYEMAT-FRPPFEARTMQELRYKVCRGKFPPIPPVYSQDLQQIIRSLLQVNPK 242
                       250
                ....*....|.
gi 15718680 601 DRPAFSRLLRQ 611
Cdd:cd08530 243 KRPSCDKLLQS 253
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
365-610 4.10e-25

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK 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: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 105.13  E-value: 4.10e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWL-NKDKVAIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd06610   5 LIEVIGSGATAVVYAAYCLpKKEKVAIKRIDLEKCQTsmDELRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLLSGG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQ--RGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD-QYTSSTGT 518
Cdd:cd06610  85 SLLDIMKSSypRGGLDEAIIATVLKEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSASLATGgDRTRKVRK 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 KF---PVkWASPEVFSFSR-YSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGfrlYKPRL---ASTHVY--- 588
Cdd:cd06610 165 TFvgtPC-WMAPEVMEQVRgYDFKADIWSFGITAIEL-ATGAAPYSKYPPMKVLMLTLQN---DPPSLetgADYKKYsks 239
                       250       260
                ....*....|....*....|....
gi 15718680 589 --QIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd06610 240 frKMISLCLQKDPSKRPTAEELLK 263
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
364-553 4.49e-25

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: 105.31  E-value: 4.49e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYWL-NKDKVAIKTIREGAMSEEDFIEEAEV--MMKL-SHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd07830   2 KVIKQLGDGTFGSVYLARNKeTGELVAIKKMKKKFYSWEECMNLREVksLRKLnEHPNIVKLKEVFRENDELYFVFEYME 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGcLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD-DQYTSSTG 517
Cdd:cd07830  82 GN-LYQLMKDRKGkPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRSrPPYTDYVS 160
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 15718680 518 TkfpvKW-ASPEVFSFSR-YSSKSDVWSFGVLMWEVFS 553
Cdd:cd07830 161 T----RWyRAPEILLRSTsYSSPVDIWALGCIMAELYT 194
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
369-553 4.53e-25

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: 104.62  E-value: 4.53e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLN-KDKVAIKTIREGAMSEEDFIEEAEVMMKL----SHPKLVQLYGVCLEQAP--ICLVFEFMEHG 441
Cdd:cd05118   7 IGEGAFGTVWLARDKVtGEKVAIKKIKNDFRHPKAALREIKLLKHLndveGHPNIVKLLDVFEHRGGnhLCLVFELMGMN 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 cLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV-GENQVIKVSDFGMTRFVLDDQYTSSTGTKF 520
Cdd:cd05118  87 -LYELIKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILInLELGQLKLADFGLARSFTSPPYTPYVATRW 165
                       170       180       190
                ....*....|....*....|....*....|....
gi 15718680 521 pvkWASPEV-FSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd05118 166 ---YRAPEVlLGAKPYGSSIDIWSLGCILAELLT 196
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
175-228 9.45e-25

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. 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 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. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212702 [Multi-domain]  Cd Length: 54  Bit Score: 96.96  E-value: 9.45e-25
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 15718680 175 VVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVE 228
Cdd:cd11768   1 IVVALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRARDKNGNEGYIPSNYVTE 54
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
361-609 1.40e-24

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: 103.58  E-value: 1.40e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEED--FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd06605   1 DDLEYLGELGEGNGGVVSKVRHRPSGQImAVKVIRLEIDEALQkqILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQRGLfaAETLLG-MCLDVCEGMAYLEEAC-VIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd06605  81 MDGGSLDKILKEVGRI--PERILGkIAVAVVKGLIYLHEKHkIIHRDVKPSNILVNSRGQVKLCDFGVSGQLVDSLAKTF 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 TGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENrsnsEVVEDISTGFRLYK-------PRLAStHVY 588
Cdd:cd06605 159 VGTR---SYMAPERISGGKYTVKSDIWSLGLSLVEL-ATGRFPYPP----PNAKPSMMIFELLSyivdeppPLLPS-GKF 229
                       250       260
                ....*....|....*....|....*.
gi 15718680 589 -----QIMNHCWKERPEDRPAFSRLL 609
Cdd:cd06605 230 spdfqDFVSQCLQKDPTERPSYKELM 255
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
369-605 1.54e-24

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: 103.07  E-value: 1.54e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTI---REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14009   1 IGRGSFATVWKGRHKQTGEvVAIKEIsrkKLNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARNCLV---GENQVIKVSDFGMTRFvLDDQYTSSTGTKFP 521
Cdd:cd14009  81 QYIRKRGRLPEAVARHFM-QQLASGLKFLRSKNIIHRDLKPQNLLLstsGDDPVLKIADFGFARS-LQPASMAETLCGSP 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 522 VKWAsPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG---FRLYKPRLASTHVYQIMNHCWKER 598
Cdd:cd14009 159 LYMA-PEILQFQKYDAKADLWSVGAILFEMLV-GKPPFRGSNHVQLLRNIERSdavIPFPIAAQLSPDCKDLLRRLLRRD 236

                ....*..
gi 15718680 599 PEDRPAF 605
Cdd:cd14009 237 PAERISF 243
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
369-574 1.82e-24

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: 103.24  E-value: 1.82e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNK-DKVAIKTI---------REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFM 438
Cdd:cd14084  14 LGSGACGEVKLAYDKSTcKKVAIKIInkrkftigsRREINKPRNIETEIEILKKLSHPCIIKIEDFFDAEDDYYIVLELM 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQRGLFAAETLL---GMCLDVcegmAYLEEACVIHRDLAARNCLVGENQ---VIKVSDFGMTRFVLDDQY 512
Cdd:cd14084  94 EGGELFDRVVSNKRLKEAICKLyfyQMLLAV----KYLHSNGIIHRDLKPENVLLSSQEeecLIKITDFGLSKILGETSL 169
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 513 TSS-TGTkfpVKWASPEVF-SFSR--YSSKSDVWSFGVLMWEVFSeGKIPY-ENRSNSEVVEDISTG 574
Cdd:cd14084 170 MKTlCGT---PTYLAPEVLrSFGTegYTRAVDCWSLGVILFICLS-GYPPFsEEYTQMSLKEQILSG 232
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
366-611 2.31e-24

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: 102.73  E-value: 2.31e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGywlnKDKV-----AIKTIREGAMS-EEDFIEEAEVMM--KLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd08225   5 IKKIGEGSFGKIYLA----KAKSdsehcVIKEIDLTKMPvKEKEASKKEVILlaKMKHPNIVTFFASFQENGRLFIVMEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGEN-QVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd08225  81 CDGGDLMKRINRQRGvLFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNgMVAKLGDFGIARQLNDSMELAY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 T--GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTG-FRLYKPRLaSTHVYQIMN 592
Cdd:cd08225 161 TcvGTPY---YLSPEICQNRPYNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGyFAPISPNF-SRDLRSLIS 235
                       250
                ....*....|....*....
gi 15718680 593 HCWKERPEDRPAFSRLLRQ 611
Cdd:cd08225 236 QLFKVSPRDRPSITSILKR 254
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
365-595 8.52e-24

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: 100.93  E-value: 8.52e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAM-SEEDFI---EEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd14073   5 LLETLGKGTYGKVKLAIERATGReVAIKSIKKDKIeDEQDMVrirREIEIMSSLNHPHIIRIYEVFENKDKIVIVMEYAS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGLFAAETlLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTsSTGTK 519
Cdd:cd14073  85 GGELYDYISERRRLPEREA-RRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKDKLL-QTFCG 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 520 FPVkWASPEVFSFSRYSS-KSDVWSFGVLMWE-VFseGKIPYENRSNSEVVEDISTGfRLYKPRLASTH----------- 586
Cdd:cd14073 163 SPL-YASPEIVNGTPYQGpEVDCWSLGVLLYTlVY--GTMPFDGSDFKRLVKQISSG-DYREPTQPSDAsglirwmltvn 238
                       250
                ....*....|....*
gi 15718680 587 ------VYQIMNHCW 595
Cdd:cd14073 239 pkrratIEDIANHWW 253
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
362-618 1.19e-23

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: 100.86  E-value: 1.19e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWlnKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVcLEQAPICLVFEFM 438
Cdd:cd14150   1 EVSMLKRIGTGSFGTVFRGKW--HGDVAVKILKVTEPTPEQlqaFKNEMQVLRKTRHVNILLFMGF-MTRPNFAIITQWC 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM----TRFVLDDQYTS 514
Cdd:cd14150  78 EGSSLYRHLHVTETRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLatvkTRWSGSQQVEQ 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 STGTkfpVKWASPEVFSF---SRYSSKSDVWSFGVLMWEVFSeGKIPYENRSN-SEVVEDISTGFrlYKPRLASTH---- 586
Cdd:cd14150 158 PSGS---ILWMAPEVIRMqdtNPYSFQSDVYAYGVVLYELMS-GTLPYSNINNrDQIIFMVGRGY--LSPDLSKLSsncp 231
                       250       260       270
                ....*....|....*....|....*....|....
gi 15718680 587 --VYQIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd14150 232 kaMKRLLIDCLKFKREERPLFPQILVSIELLQRL 265
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
367-610 1.32e-23

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: 100.55  E-value: 1.32e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGywLNKDK---VAIKTIR---EGAMSEEDFIE-EAEVMM--KLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd06632   6 QLLGSGSFGSVYEG--FNGDTgdfFAVKEVSlvdDDKKSRESVKQlEQEIALlsKLRHPNIVQYYGTEREEDNLYIFLEY 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS-T 516
Cdd:cd06632  84 VPGGSIHKLLQ-RYGAFEEPVIRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVEAFSFAKSfK 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 GTKFpvkWASPEVFS--FSRYSSKSDVWSFGVLMWEVfSEGKIPYenrSNSEVVEDIstgFRLYK-------PRLASTHV 587
Cdd:cd06632 163 GSPY---WMAPEVIMqkNSGYGLAVDIWSLGCTVLEM-ATGKPPW---SQYEGVAAI---FKIGNsgelppiPDHLSPDA 232
                       250       260
                ....*....|....*....|...
gi 15718680 588 YQIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd06632 233 KDFIRLCLQRDPEDRPTASQLLE 255
SH2 pfam00017
SH2 domain;
239-323 1.40e-23

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 94.59  E-value: 1.40e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   239 WYNKSISRDKAEKLLLDTGKEGAFMVRDS-RTAGTYTVSVFTKAVVsennpciKHYHIKETNDnpKRYYVAEKYVFDSIP 317
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESeSTPGGYTLSVRDDGKV-------KHYKIQSTDN--GGYYISGGVKFSSLA 71

                  ....*.
gi 15718680   318 LLINYH 323
Cdd:pfam00017  72 ELVEHY 77
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
369-609 1.41e-23

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: 100.43  E-value: 1.41e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKD-KVAIKTIR--EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 445
Cdd:cd08219   8 VGEGSFGRALLVQHVNSDqKYAMKEIRlpKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEYCDGGDLMQ 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST--GTKFpv 522
Cdd:cd08219  88 KIKLQRGkLFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTSPGAYACTyvGTPY-- 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 523 kWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTGfrLYKPrLASTHVYQ---IMNHCWKERP 599
Cdd:cd08219 166 -YVPPEIWENMPYNNKSDIWSLGCILYELCTL-KHPFQANSWKNLILKVCQG--SYKP-LPSHYSYElrsLIKQMFKRNP 240
                       250
                ....*....|
gi 15718680 600 EDRPAFSRLL 609
Cdd:cd08219 241 RSRPSATTIL 250
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
358-610 1.97e-23

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: 100.59  E-value: 1.97e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSEL-TFVQEIGSGQFGLVHLGYWLNKD-KVAIKTIREGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd06611   1 VNPNDIwEIIGELGDGAFGKVYKAQHKETGlFAAAKIIQIESEEElEDFMVEIDILSECKHPNIVGLYEAYFYENKLWIL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSD-YLRTQRGLFAAEtLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd06611  81 IEFCDGGALDSiMLELERGLTEPQ-IRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSAKNKSTLQK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SST--GTKFpvkWASPEV-----FSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDI--STGFRLYKPRLAS 584
Cdd:cd06611 160 RDTfiGTPY---WMAPEVvacetFKDNPYDYKADIWSLGITLIEL-AQMEPPHHELNPMRVLLKIlkSEPPTLDQPSKWS 235
                       250       260
                ....*....|....*....|....*.
gi 15718680 585 THVYQIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd06611 236 SSFNDFLKSCLVKDPDDRPTAAELLK 261
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
401-612 2.56e-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: 99.59  E-value: 2.56e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 401 EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPIcLVFEFMEHGCLSDYLRTQ--RGLFAAETLLGMCLDVCEGMAYLEEACV 478
Cdd:cd14208  47 ESFLEAASIMSQISHKHLVLLHGVCVGKDSI-MVQEFVCHGALDLYLKKQqqKGPVAISWKLQVVKQLAYALNYLEDKQL 125
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 479 IHRDLAARNCLV------GENQVIKVSDFGMTRFVLDDQYTSSTgtkfpVKWASPEVFSFSR-YSSKSDVWSFGVLMWEV 551
Cdd:cd14208 126 VHGNVSAKKVLLsregdkGSPPFIKLSDPGVSIKVLDEELLAER-----IPWVAPECLSDPQnLALEADKWGFGATLWEI 200
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 552 FSEGKIPYEnrsnsevVEDISTGFRLYKPRLAS-----THVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd14208 201 FSGGHMPLS-------ALDPSKKLQFYNDRKQLpaphwIELASLIQQCMSYNPLLRPSFRAIIRDL 259
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
367-610 2.83e-23

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: 99.76  E-value: 2.83e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNK-DKVAIK------TIREGAMSEEDFI-----EEAEVMMKLSHPKLVQLYGvCLEQAPICLV 434
Cdd:cd06629   7 ELIGKGTYGRVYLAMNATTgEMLAVKqvelpkTSSDRADSRQKTVvdalkSEIDTLKDLDHPNIVQYLG-FEETEDYFSI 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 F-EFMEHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD---- 509
Cdd:cd06629  86 FlEYVPGGSIGSCLRKY-GKFEEDLVRFFTRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISKKSDDiygn 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGTKFpvkWASPEVFSFSR--YSSKSDVWSFGVLMWEVFSeGKIPYenrSNSEVVEDIstgFRLYKPRLA---- 583
Cdd:cd06629 165 NGATSMQGSVF---WMAPEVIHSQGqgYSAKVDIWSLGCVVLEMLA-GRRPW---SDDEAIAAM---FKLGNKRSAppvp 234
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 584 -----STHVYQIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd06629 235 edvnlSPEALDFLNACFAIDPRDRPTAAELLS 266
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
356-618 2.96e-23

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: 100.11  E-value: 2.96e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIDPSELTFVQEIGSGQFGLVHLGYWlnKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVcLEQAPIC 432
Cdd:cd14149   7 WEIEASEVMLSTRIGSGSFGTVYKGKW--HGDVAVKILKVVDPTPEQfqaFRNEVAVLRKTRHVNILLFMGY-MTKDNLA 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM----TRFVL 508
Cdd:cd14149  84 IVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLatvkSRWSG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTkfpVKWASPEVFSF---SRYSSKSDVWSFGVLMWEVFSeGKIPYEN-RSNSEVVEDISTGF------RLY 578
Cdd:cd14149 164 SQQVEQPTGS---ILWMAPEVIRMqdnNPFSFQSDVYSYGIVLYELMT-GELPYSHiNNRDQIIFMVGRGYaspdlsKLY 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 15718680 579 KPrlASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd14149 240 KN--CPKAMKRLVADCIKKVKEERPLFPQILSSIELLQHS 277
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
341-611 3.40e-23

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: 100.50  E-value: 3.40e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 341 GRQKAPVTAGLRYGKwviDPSELtFV--QEIGSGQFGLVHLGYWLNKDK-VAIKTIR-EGAMSEE---DFIEEAEVMMKL 413
Cdd:cd06633   3 GVLKDPEIADLFYKD---DPEEI-FVdlHEIGHGSFGAVYFATNSHTNEvVAIKKMSySGKQTNEkwqDIIKEVKFLQQL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 414 SHPKLVQLYGVCLEQAPICLVFEFMeHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGEN 493
Cdd:cd06633  79 KHPNTIEYKGCYLKDHTAWLVMEYC-LGSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEP 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 494 QVIKVSDFGMTRFVldDQYTSSTGTKFpvkWASPEV---FSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVED 570
Cdd:cd06633 158 GQVKLADFGSASIA--SPANSFVGTPY---WMAPEVilaMDEGQYDGKVDIWSLGITCIEL-AERKPPLFNMNAMSALYH 231
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 15718680 571 ISTGfrlYKPRLASTH----VYQIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06633 232 IAQN---DSPTLQSNEwtdsFRGFVDYCLQKIPQERPSSAELLRH 273
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
359-611 3.70e-23

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: 99.74  E-value: 3.70e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL-TFVQEIGSGQFGLVHLGY-WLNKDKVAIKTIR-EGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd06640   1 DPEELfTKLERIGKGSFGEVFKGIdNRTQQVVAIKIIDlEEAEDEiEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTqrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd06640  81 MEYLGGGSALDLLRA--GPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 ST--GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDIStgfRLYKPRLA---STHVYQ 589
Cdd:cd06640 159 NTfvGTPF---WMAPEVIQQSAYDSKADIWSLGITAIEL-AKGEPPNSDMHPMRVLFLIP---KNNPPTLVgdfSKPFKE 231
                       250       260
                ....*....|....*....|..
gi 15718680 590 IMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06640 232 FIDACLNKDPSFRPTAKELLKH 253
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
358-610 4.12e-23

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: 99.82  E-value: 4.12e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAP-ICL 433
Cdd:cd06620   2 LKNQDLETLKDLGAGNGGSVSKVLHIPTGTImAKKVIHIDAKSSvrKQILRELQILHECHSPYIVSFYGAFLNENNnIII 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYL-EEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd06620  82 CMEYMDCGSLDKILK-KKGPFPEEVLGKIAVAVLEGLTYLyNVHRIIHRDIKPSNILVNSKGQIKLCDFGVSGELINSIA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGF-------------RLYK 579
Cdd:cd06620 161 DTFVGTS---TYMSPERIQGGKYSVKSDVWSLGLSIIELAL-GEFPFAGSNDDDDGYNGPMGIldllqrivnepppRLPK 236
                       250       260       270
                ....*....|....*....|....*....|.
gi 15718680 580 PRLASTHVYQIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd06620 237 DRIFPKDLRDFVDRCLLKDPRERPSPQLLLD 267
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
403-612 4.80e-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: 99.23  E-value: 4.80e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 403 FIEEAEVMMKLSHPKLVQLYGVCLEqaPICLVFEFMEHGCLSDYLRTQRGLFAA---ETLLGMCLDVCEGMAYLEEACVI 479
Cdd:cd14000  57 LRQELTVLSHLHHPSIVYLLGIGIH--PLMLVLELAPLGSLDHLLQQDSRSFASlgrTLQQRIALQVADGLRYLHSAMII 134
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 480 HRDLAARNCLVGENQV-----IKVSDFGMTRFVLDDQYTSSTGTKfpvKWASPEVFSFS-RYSSKSDVWSFGVLMWEVFS 553
Cdd:cd14000 135 YRDLKSHNVLVWTLYPnsaiiIKIADYGISRQCCRMGAKGSEGTP---GFRAPEIARGNvIYNEKVDVFSFGMLLYEILS 211
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680 554 eGKIPYENRSNSEVVEDISTGFR--LYKPRLAS-THVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd14000 212 -GGAPMVGHLKFPNEFDIHGGLRppLKQYECAPwPEVEVLMKKCWKENPQQRPTAVTVVSIL 272
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
361-559 5.48e-23

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: 99.24  E-value: 5.48e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIR-EGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd06609   1 ELFTLLERIGKGSFGEVYKGIDKRTNQvVAIKVIDlEEAEDEiEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRtqRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTrfvldDQYTSST- 516
Cdd:cd06609  81 CGGGSVLDLLK--PGPLDETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVS-----GQLTSTMs 153
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 517 ------GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPY 559
Cdd:cd06609 154 krntfvGTPF---WMAPEVIKQSGYDEKADIWSLGITAIELAK-GEPPL 198
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
393-608 7.37e-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: 7.37e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 393 IREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAY 472
Cdd:cd14221  27 IRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSHYPWSQRVSFAKDIASGMAY 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 473 LEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVK-------------WASPEVFSFSRYSSKS 539
Cdd:cd14221 107 LHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDEKTQPEGLRSLKKPdrkkrytvvgnpyWMAPEMINGRSYDEKV 186
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 540 DVWSFGVLMWEVFseGKI----PYENRSnSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRL 608
Cdd:cd14221 187 DVFSFGIVLCEII--GRVnadpDYLPRT-MDFGLNVRGFLDRYCPPNCPPSFFPIAVLCCDLDPEKRPSFSKL 256
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
363-612 1.56e-22

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: 97.33  E-value: 1.56e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGY--------WLNKDKVAIKTIREGAMS-EEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICL 433
Cdd:cd05078   1 LIFNESLGQGTFTKIFKGIrrevgdygQLHETEVLLKVLDKAHRNySESFFEAASMMSQLSHKHLVLNYGVCVCGDENIL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV--------GENQVIKVSDFGMTR 505
Cdd:cd05078  81 VQEYVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEEKTLVHGNVCAKNILLireedrktGNPPFIKLSDPGISI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 FVLDDQYTSSTgtkfpVKWASPEVFSFSRY-SSKSDVWSFGVLMWEVFSEGKIP---YENRSNSEVVEDistgfRLYKPR 581
Cdd:cd05078 161 TVLPKDILLER-----IPWVPPECIENPKNlSLATDKWSFGTTLWEICSGGDKPlsaLDSQRKLQFYED-----RHQLPA 230
                       250       260       270
                ....*....|....*....|....*....|.
gi 15718680 582 LASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05078 231 PKWTELANLINNCMDYEPDHRPSFRAIIRDL 261
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
403-612 2.21e-22

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: 97.29  E-value: 2.21e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 403 FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRD 482
Cdd:cd05076  62 FFETASLMSQVSHTHLVFVHGVCVRGSENIMVEEFVEHGPLDVWLRKEKGHVPMAWKFVVARQLASALSYLENKNLVHGN 141
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 483 LAARNCLV-------GENQVIKVSDFGMTRFVLDDQYTSSTgtkfpVKWASPE-VFSFSRYSSKSDVWSFGVLMWEVFSE 554
Cdd:cd05076 142 VCAKNILLarlgleeGTSPFIKLSDPGVGLGVLSREERVER-----IPWIAPEcVPGGNSLSTAADKWGFGATLLEICFN 216
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 555 GKIPYENRSNSEVVEDISTGFRLYKPrlASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05076 217 GEAPLQSRTPSEKERFYQRQHRLPEP--SCPELATLISQCLTYEPTQRPSFRTILRDL 272
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
365-574 2.28e-22

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: 96.95  E-value: 2.28e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAM-SEEDFIE---EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd14161   7 FLETLGKGTYGRVKKARDSSGRLVAIKSIRKDRIkDEQDLLHirrEIEIMSSLNHPHIISVYEVFENSSKIVIVMEYASR 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQRGLFAAETLlGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTsSTGTKF 520
Cdd:cd14161  87 GDLYDYISERQRLSELEAR-HFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDKFL-QTYCGS 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15718680 521 PVkWASPEVFSFSRYSS-KSDVWSFGVLMWeVFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd14161 165 PL-YASPEIVNGRPYIGpEVDSWSLGVLLY-ILVHGTMPFDGHDYKILVKQISSG 217
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
369-610 3.40e-22

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: 96.27  E-value: 3.40e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE------EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd06625   8 LGQGAFGQVYLCYDADTGReLAVKQVEIDPINTEASKEvkalecEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEYMPGG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGLfaAETLLG-MCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR----FVLDDQYTSST 516
Cdd:cd06625  88 SVKDEIKAYGAL--TENVTRkYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKrlqtICSSTGMKSVT 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTGFRLYK-PRLASTHVYQIMNHCW 595
Cdd:cd06625 166 GTPY---WMSPEVINGEGYGRKADIWSVGCTVVEMLTT-KPPWAEFEPMAAIFKIATQPTNPQlPPHVSEDARDFLSLIF 241
                       250
                ....*....|....*
gi 15718680 596 KERPEDRPAFSRLLR 610
Cdd:cd06625 242 VRNKKQRPSAEELLS 256
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
369-610 3.80e-22

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: 96.39  E-value: 3.80e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEED-----FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd14098   8 LGSGTFAEVKKAVEVETGKMrAIKQIVKRKVAGNDknlqlFQREINILKSLEHPGIVRLIDWYEDDQHIYLVMEYVEGGD 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGL--FAAETLLgmcLDVCEGMAYLEEACVIHRDLAARNCLVGENQ--VIKVSDFGMTRFVLDDQYTSS-TG 517
Cdd:cd14098  88 LMDFIMAWGAIpeQHARELT---KQILEAMAYTHSMGITHRDLKPENILITQDDpvIVKISDFGLAKVIHTGTFLVTfCG 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TkfpVKWASPEVFsFSR-------YSSKSDVWSFGVLMWeVFSEGKIPYENRSNSEVVEDISTGfRLYKPRLASTHVYQ- 589
Cdd:cd14098 165 T---MAYLAPEIL-MSKeqnlqggYSNLVDMWSVGCLVY-VMLTGALPFDGSSQLPVEKRIRKG-RYTQPPLVDFNISEe 238
                       250       260
                ....*....|....*....|....
gi 15718680 590 ---IMNHCWKERPEDRPAFSRLLR 610
Cdd:cd14098 239 aidFILRLLDVDPEKRMTAAQALD 262
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
359-610 4.34e-22

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: 95.97  E-value: 4.34e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DP-SELTFVQEIGSGQFGLVHLGYWLNKD-KVAIKT--IREGAMSEEDFiEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd06648   4 DPrSDLDNFVKIGEGSTGIVCIATDKSTGrQVAVKKmdLRKQQRRELLF-NEVVIMRDYQHPNIVEMYSSYLVGDELWVV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD--QY 512
Cdd:cd06648  83 MEFLEGGALTDIVTHTR--MNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKEvpRR 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTGF--RLYKPRLASTHVYQI 590
Cdd:cd06648 161 KSLVGTPY---WMAPEVISRLPYGTEVDIWSLGIMVIEMV-DGEPPYFNEPPLQAMKRIRDNEppKLKNLHKVSPRLRSF 236
                       250       260
                ....*....|....*....|
gi 15718680 591 MNHCWKERPEDRPAFSRLLR 610
Cdd:cd06648 237 LDRMLVRDPAQRATAAELLN 256
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
369-561 4.53e-22

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: 95.83  E-value: 4.53e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLN-KDKVAIKTIREGAMSEeDFIE-----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd14162   8 LGHGSYAVVKKAYSTKhKCKVAIKIVSKKKAPE-DYLQkflprEIEVIKGLKHPNLICFYEAIETTSRVYIIMELAENGD 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGLFAAETLLGMClDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG---------MTRFVLDDQYT 513
Cdd:cd14162  87 LLDYIRKNGALPEPQARRWFR-QLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGfargvmktkDGKPKLSETYC 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 514 SSTGtkfpvkWASPEVFSFSRYSSK-SDVWSFGVLMWEVFSeGKIPYEN 561
Cdd:cd14162 166 GSYA------YASPEILRGIPYDPFlSDIWSMGVVLYTMVY-GRLPFDD 207
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
369-574 4.87e-22

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: 95.78  E-value: 4.87e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLG-YWLNKDKVAIKTIREGAMSEED---FIEEAEVMMKL-SHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14081   9 LGKGQTGLVKLAkHCVTGQKVAIKIVNKEKLSKESvlmKVEREIAIMKLiEHPNVLKLYDVYENKKYLYLVLEYVSGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAETL--LGMCLDvceGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY-TSSTGTkf 520
Cdd:cd14081  89 FDYLVKKGRLTEKEARkfFRQIIS---ALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMASLQPEGSLlETSCGS-- 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15718680 521 PvKWASPEVFSFSRY-SSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd14081 164 P-HYACPEVIKGEKYdGRKADIWSCGVILYALLV-GALPFDDDNLRQLLEKVKRG 216
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
365-609 6.32e-22

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: 95.41  E-value: 6.32e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEdFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd06612   7 ILEKLGEGSYGSVYKAIHKETGQvVAIKVVPVEEDLQE-IIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYCGAGSV 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLR-TQRGLFAAETLLgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST--GTKF 520
Cdd:cd06612  86 SDIMKiTNKTLTEEEIAA-ILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTDTMAKRNTviGTPF 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 pvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDIST----GFRlyKPRLASTHVYQIMNHCWK 596
Cdd:cd06612 165 ---WMAPEVIQEIGYNNKADIWSLGITAIEMA-EGKPPYSDIHPMRAIFMIPNkpppTLS--DPEKWSPEFNDFVKKCLV 238
                       250
                ....*....|...
gi 15718680 597 ERPEDRPAFSRLL 609
Cdd:cd06612 239 KDPEERPSAIQLL 251
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
403-612 7.17e-22

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: 95.77  E-value: 7.17e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 403 FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRD 482
Cdd:cd05077  55 FFETASMMRQVSHKHIVLLYGVCVRDVENIMVEEFVEFGPLDLFMHRKSDVLTTPWKFKVAKQLASALSYLEDKDLVHGN 134
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 483 LAARNCLVGENQV-------IKVSDFGMTRFVLDDQYTSSTgtkfpVKWASPEVFSFSR-YSSKSDVWSFGVLMWEVFSE 554
Cdd:cd05077 135 VCTKNILLAREGIdgecgpfIKLSDPGIPITVLSRQECVER-----IPWIAPECVEDSKnLSIAADKWSFGTTLWEICYN 209
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 555 GKIPYENRSNSEVVEDISTGFRLYKPrlASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd05077 210 GEIPLKDKTLAEKERFYEGQCMLVTP--SCKELADLMTHCMNYDPNQRPFFRAIMRDI 265
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
369-610 8.59e-22

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: 95.58  E-value: 8.59e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTI------REGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd06631   9 LGKGAYGTVYCGLTSTGQLIAVKQVeldtsdKEKAEKEyEKLQEEVDLLKTLKHVNIVGYLGTCLEDNVVSIFMEFVPGG 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST----- 516
Cdd:cd06631  89 SIASILA-RFGALEEPVFCRYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLCINLSSGSQsqllk 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 ---GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLyKPRL---ASTHVYQI 590
Cdd:cd06631 168 smrGTPY---WMAPEVINETGHGRKSDIWSIGCTVFEMAT-GKPPWADMNPMAAIFAIGSGRKP-VPRLpdkFSPEARDF 242
                       250       260
                ....*....|....*....|
gi 15718680 591 MNHCWKERPEDRPAFSRLLR 610
Cdd:cd06631 243 VHACLTRDQDERPSAEQLLK 262
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
355-609 9.00e-22

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: 95.02  E-value: 9.00e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTfvQEIGSGQFGLVHLGY-----WLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQA 429
Cdd:cd14116   1 QWALEDFEIG--RPLGKGKFGNVYLARekqskFILALKVLFKAQLEKAGVEHQLRREVEIQSHLRHPNILRLYGYFHDAT 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEHGCLsdYLRTQR-GLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL 508
Cdd:cd14116  79 RVYLILEYAPLGTV--YRELQKlSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVHAP 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPYENRSNSEVVEDISTGFRLYkPRLASTHVY 588
Cdd:cd14116 157 SSRRTTLCGT---LDYLPPEMIEGRMHDEKVDLWSLGVLCYE-FLVGKPPFEANTYQETYKRISRVEFTF-PDFVTEGAR 231
                       250       260
                ....*....|....*....|.
gi 15718680 589 QIMNHCWKERPEDRPAFSRLL 609
Cdd:cd14116 232 DLISRLLKHNPSQRPMLREVL 252
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
365-610 1.08e-21

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: 94.92  E-value: 1.08e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHlgywlnkdKV---------AIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYG--VCLEQAP 430
Cdd:cd08217   4 VLETIGKGSFGTVR--------KVrrksdgkilVWKEIDYGKMSEKEkqqLVSEVNILRELKHPNIVRYYDriVDRANTT 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGCLSDYL---RTQRGLFAAETLLGMCLDVCEGMAYleeaC---------VIHRDLAARNCLVGENQVIKV 498
Cdd:cd08217  76 LYIVMEYCEGGDLAQLIkkcKKENQYIPEEFIWKIFTQLLLALYE----ChnrsvgggkILHRDLKPANIFLDSDNNVKL 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 499 SDFGMTRFVLDDQYTSST--GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFR 576
Cdd:cd08217 152 GDFGLARVLSHDSSFAKTyvGTPY---YMSPELLNEQSYDEKSDIWSLGCLIYELCA-LHPPFQAANQLELAKKIKEGKF 227
                       250       260       270
                ....*....|....*....|....*....|....
gi 15718680 577 LYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd08217 228 PRIPSRYSSELNEVIKSMLNVDPDKRPSVEELLQ 261
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
369-550 1.11e-21

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: 95.72  E-value: 1.11e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEE----DF--IEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEhG 441
Cdd:cd07841   8 LGEGTYAVVYKARDKETGRiVAIKKIKLGERKEAkdgiNFtaLREIKLLQELKHPNIIGLLDVFGHKSNINLVFEFME-T 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGLFAA---ETLLGMCLdvcEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD--QYTSST 516
Cdd:cd07841  87 DLEKVIKDKSIVLTPadiKSYMLMTL---RGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLARSFGSPnrKMTHQV 163
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15718680 517 GTKFpvkWASPEVFSFSR-YSSKSDVWSFGVLMWE 550
Cdd:cd07841 164 VTRW---YRAPELLFGARhYGVGVDMWSVGCIFAE 195
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
369-617 1.14e-21

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: 94.85  E-value: 1.14e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLR 448
Cdd:cd14155   1 IGSGFFSEVYKVRHRTSGQVMALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGNLEQLLD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 449 TQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV--GENQVIK-VSDFGMTRFVLDDQYTSStgtKFPV--- 522
Cdd:cd14155  81 SNEPL-SWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrDENGYTAvVGDFGLAEKIPDYSDGKE---KLAVvgs 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 523 -KWASPEVFSFSRYSSKSDVWSFGVLMWEVFseGKIP----YENRSNS---------EVVEDISTGFrlykprlasthvY 588
Cdd:cd14155 157 pYWMAPEVLRGEPYNEKADVFSYGIILCEII--ARIQadpdYLPRTEDfgldydafqHMVGDCPPDF------------L 222
                       250       260
                ....*....|....*....|....*....
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQLAEIAE 617
Cdd:cd14155 223 QLAFNCCNMDPKSRPSFHDIVKTLEEILE 251
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
369-610 1.16e-21

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: 94.91  E-value: 1.16e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLG-YWLNKDKVAIKTIR------EGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd06628   8 IGSGSFGSVYLGmNASSGELMAVKQVElpsvsaENKDRKKSMLDalqrEIALLRELQHENIVQYLGSSSDANHLNIFLEY 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd06628  88 VPGGSVATLL-NNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANSLSTKNN 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKFP-----VKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMN 592
Cdd:cd06628 167 GARPslqgsVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFPDCTQMQAIFKIGENASPTIPSNISSEARDFLE 245
                       250
                ....*....|....*...
gi 15718680 593 HCWKERPEDRPAFSRLLR 610
Cdd:cd06628 246 KTFEIDHNKRPTADELLK 263
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
369-560 1.42e-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: 94.38  E-value: 1.42e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLG-YWLNKDKVAIKTIREGAMSEEDF---IEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14071   8 IGKGNFAVVKLArHRITKTEVAIKIIDKSQLDEENLkkiYREVQIMKMLNHPHIIKLYQVMETKDMLYLVTEYASNGEIF 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPvkW 524
Cdd:cd14071  88 DYL-AQHGRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKPGELLKTWCGSPP--Y 164
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15718680 525 ASPEVFSFSRYSS-KSDVWSFGVLMWeVFSEGKIPYE 560
Cdd:cd14071 165 AAPEVFEGKEYEGpQLDIWSLGVVLY-VLVCGALPFD 200
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
359-611 1.64e-21

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: 94.75  E-value: 1.64e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL-TFVQEIGSGQFGLVHLGY-WLNKDKVAIKTI--REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd06641   1 DPEELfTKLEKIGKGSFGEVFKGIdNRTQKVVAIKIIdlEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLrtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd06641  81 MEYLGGGSALDLL--EPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 S--TGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMN 592
Cdd:cd06641 159 N*fVGTPF---WMAPEVIKQSAYDSKADIWSLGITAIEL-ARGEPPHSELHPMKVLFLIPKNNPPTLEGNYSKPLKEFVE 234
                       250
                ....*....|....*....
gi 15718680 593 HCWKERPEDRPAFSRLLRQ 611
Cdd:cd06641 235 ACLNKEPSFRPTAKELLKH 253
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
359-611 1.80e-21

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: 94.74  E-value: 1.80e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL-TFVQEIGSGQFGLVHLGYW-LNKDKVAIKTIR-EGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd06642   1 DPEELfTKLERIGKGSFGEVYKGIDnRTKEVVAIKIIDlEEAEDEiEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTqrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd06642  81 MEYLGGGSALDLLKP--GPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 ST--GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGfrlYKPRLASTH---VYQ 589
Cdd:cd06642 159 NTfvGTPF---WMAPEVIKQSAYDFKADIWSLGITAIEL-AKGEPPNSDLHPMRVLFLIPKN---SPPTLEGQHskpFKE 231
                       250       260
                ....*....|....*....|..
gi 15718680 590 IMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06642 232 FVEACLNKDPRFRPTAKELLKH 253
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
367-609 1.95e-21

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: 93.99  E-value: 1.95e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLG-YWLNKDKVAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14078   9 ETIGSGGFAKVKLAtHILTGEKVAIKIMDKKALGDDlpRVKTEIEALKNLSHQHICRLYHVIETDNKIFMVLEYCPGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAETLlGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM---TRFVLDDQYTSSTGTkf 520
Cdd:cd14078  89 FDYIVAKDRLSEDEAR-VFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLcakPKGGMDHHLETCCGS-- 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 PVkWASPEVFSFSRY-SSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfRLYKPRLASTHVYQIMNHCWKERP 599
Cdd:cd14078 166 PA-YAAPELIQGKPYiGSEADVWSMGVLLYALLC-GFLPFDDDNVMALYRKIQSG-KYEEPEWLSPSSKLLLDQMLQVDP 242
                       250
                ....*....|
gi 15718680 600 EDRPAFSRLL 609
Cdd:cd14078 243 KKRITVKELL 252
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
362-611 2.57e-21

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: 93.66  E-value: 2.57e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHL--------GYWLNKDKVAIKTIREGAMSEEdfieEAEVMMKLSHPKLVQlYGVCLE--QAPI 431
Cdd:cd08223   1 EYQFLRVIGKGSYGEVWLvrhkrdrkQYVIKKLNLKNASKRERKAAEQ----EAKLLSKLKHPNIVS-YKESFEgeDGFL 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDYLRTQRGLFAAET-LLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVLDD 510
Cdd:cd08223  76 YIVMGFCEGGDLYTRLKEQKGVLLEERqVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIAR-VLES 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 QYTSST---GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHV 587
Cdd:cd08223 155 SSDMATtliGTPY---YMSPELFSNKPYNHKSDVWALGCCVYEM-ATLKHAFNAKDMNSLVYKILEGKLPPMPKQYSPEL 230
                       250       260
                ....*....|....*....|....
gi 15718680 588 YQIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd08223 231 GELIKAMLHQDPEKRPSVKRILRQ 254
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
366-611 4.41e-21

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: 93.26  E-value: 4.41e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd08220   5 IRVVGRGAYGTVYLCRRKDDNKlVIIKQIPVEQMTKEErqaALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYAPGG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ-VIKVSDFGMTRfVLDDQYTSSTGTK 519
Cdd:cd08220  85 TLFEYIQQRKGsLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKKRtVVKIGDFGISK-ILSSKSKAYTVVG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 520 FPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERP 599
Cdd:cd08220 164 TPC-YISPELCEGKPYNQKSDIWALGCVLYEL-ASLKRAFEAANLPALVLKIMRGTFAPISDRYSEELRHLILSMLHLDP 241
                       250
                ....*....|..
gi 15718680 600 EDRPAFSRLLRQ 611
Cdd:cd08220 242 NKRPTLSEIMAQ 253
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
359-611 4.63e-21

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: 94.32  E-value: 4.63e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL-TFVQEIGSGQFGLVHLGYWL-NKDKVAIKTIR-EGAMSEE---DFIEEAEVMMKLSHPKLVQLYGVCLEQAPIC 432
Cdd:cd06634  12 DPEKLfSDLREIGHGSFGAVYFARDVrNNEVVAIKKMSySGKQSNEkwqDIIKEVKFLQKLRHPNTIEYRGCYLREHTAW 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMeHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVldDQY 512
Cdd:cd06634  92 LVMEYC-LGSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIM--APA 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKFpvkWASPEV---FSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGfrlYKPRLASTH--- 586
Cdd:cd06634 169 NSFVGTPY---WMAPEVilaMDEGQYDGKVDVWSLGITCIEL-AERKPPLFNMNAMSALYHIAQN---ESPALQSGHwse 241
                       250       260
                ....*....|....*....|....*.
gi 15718680 587 -VYQIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06634 242 yFRNFVDSCLQKIPQDRPTSDVLLKH 267
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
401-609 5.00e-21

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: 93.26  E-value: 5.00e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 401 EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSdYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIH 480
Cdd:cd06630  48 EAIREEIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAGGSVA-SLLSKYGAFSENVIINYTLQILRGLAYLHDNQIIH 126
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 481 RDLAARNCLV-GENQVIKVSDFGmTRFVLDDQYTSS-------TGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVF 552
Cdd:cd06630 127 RDLKGANLLVdSTGQRLRIADFG-AAARLASKGTGAgefqgqlLGT---IAFMAPEVLRGEQYGRSCDVWSVGCVIIEMA 202
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 553 SeGKIPYENrsnsevvEDISTGFRL-YK----------PRLASTHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd06630 203 T-AKPPWNA-------EKISNHLALiFKiasattpppiPEHLSPGLRDVTLRCLELQPEDRPPARELL 262
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
368-615 5.29e-21

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: 93.49  E-value: 5.29e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYWlNKDKVAIKTI--REgamsEEDFIEEAE----VMmkLSHPKLVQLY-------GVCLEqapICLV 434
Cdd:cd14056   2 TIGKGRYGEVWLGKY-RGEKVAVKIFssRD----EDSWFRETEiyqtVM--LRHENILGFIaadikstGSWTQ---LWLI 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLrtQRGLFAAETLLGMCLDVCEGMAYLEEA--------CVIHRDLAARNCLVGENQVIKVSDFG---- 502
Cdd:cd14056  72 TEYHEHGSLYDYL--QRNTLDTEEALRLAYSAASGLAHLHTEivgtqgkpAIAHRDLKSKNILVKRDGTCCIADLGlavr 149
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 503 --MTRFVLDDQYTSSTGTKfpvKWASPEV----FSFSRYSS--KSDVWSFGVLMWEVF---------SEGKIPYE----N 561
Cdd:cd14056 150 ydSDTNTIDIPPNPRVGTK---RYMAPEVlddsINPKSFESfkMADIYSFGLVLWEIArrceiggiaEEYQLPYFgmvpS 226
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680 562 RSNSEVVEDISTGFRLyKPRL--------ASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14056 227 DPSFEEMRKVVCVEKL-RPPIpnrwksdpVLRSMVKLMQECWSENPHARLTALRVKKTLAKL 287
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
237-329 5.40e-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: 87.28  E-value: 5.40e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680    237 YEWYNKSISRDKAEKLLLDTGkEGAFMVRDSRT-AGTYTVSVFTKAvvsennpCIKHYHIKETNDNpkRYYVAEKYVFDS 315
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG-DGDFLVRDSESsPGDYVLSVRVKG-------KVKHYRIRRNEDG--KFYLEGGRKFPS 70
                           90
                   ....*....|....
gi 15718680    316 IPLLINYHQHNGGG 329
Cdd:smart00252  71 LVELVEHYQKNSLG 84
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
341-612 5.43e-21

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: 94.35  E-value: 5.43e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 341 GRQKAPVTAGLRYGKwviDPSEL-TFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIR-EGAMSEE---DFIEEAEVMMKLS 414
Cdd:cd06635   7 GSLKDPDIAELFFKE---DPEKLfSDLREIGHGSFGAVYFARDVRTSEVvAIKKMSySGKQSNEkwqDIIKEVKFLQRIK 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 415 HPKLVQLYGVCLEQAPICLVFEFMeHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ 494
Cdd:cd06635  84 HPNSIEYKGCYLREHTAWLVMEYC-LGSASDLLEVHKKPLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPG 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 495 VIKVSDFGMTRFVldDQYTSSTGTKFpvkWASPEV---FSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDI 571
Cdd:cd06635 163 QVKLADFGSASIA--SPANSFVGTPY---WMAPEVilaMDEGQYDGKVDVWSLGITCIEL-AERKPPLFNMNAMSALYHI 236
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 15718680 572 STGfrlYKPRLAST----HVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd06635 237 AQN---ESPTLQSNewsdYFRNFVDSCLQKIPQDRPTSEELLKHM 278
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
369-566 5.44e-21

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: 93.14  E-value: 5.44e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLV---HLGYWLNKDKVAIKTIREGAMSEED------FIEEAEVMMKLSHPKLVQLYGVCLEQAP-ICLVFEFM 438
Cdd:cd13994   1 IGKGATSVVrivTKKNPRSGVLYAVKEYRRRDDESKRkdyvkrLTSEYIISSKLHHPNIVKVLDLCQDLHGkWCLVMEYC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQRGLFAAETLLgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGmTRFVLDDQYTSST-- 516
Cdd:cd13994  81 PGGDLFTLIEKADSLSLEEKDC-FFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFG-TAEVFGMPAEKESpm 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 517 -----GTKfpvKWASPEVFSFSRYSSKS-DVWSFGVLMWEVFSeGKIPYENRSNSE 566
Cdd:cd13994 159 saglcGSE---PYMAPEVFTSGSYDGRAvDVWSCGIVLFALFT-GRFPWRSAKKSD 210
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
359-610 7.09e-21

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: 92.75  E-value: 7.09e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL-TFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIEEAEVMMKLS-HPKLVQLYGVCLEQAPIC--- 432
Cdd:cd06608   3 DPAGIfELVEVIGEGTYGKVYKARHKKTGQlAAIKIMDIIEDEEEEIKLEINILRKFSnHPNIATFYGAFIKKDPPGgdd 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 ---LVFEFMEHGCLSDYLRT--QRGLFAAETLLG-MCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRf 506
Cdd:cd06608  83 qlwLVMEYCGGGSVTDLVKGlrKKGKRLKEEWIAyILRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSA- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 vlddQYTS-------STGTKFpvkWASPEVFSFSR-----YSSKSDVWSFGVLMWEVfSEGKIPYEN----RSNSEVVED 570
Cdd:cd06608 162 ----QLDStlgrrntFIGTPY---WMAPEVIACDQqpdasYDARCDVWSLGITAIEL-ADGKPPLCDmhpmRALFKIPRN 233
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 15718680 571 ISTgfRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd06608 234 PPP--TLKSPEKWSKEFNDFISECLIKNYEQRPFTEELLE 271
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
366-611 9.56e-21

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: 92.18  E-value: 9.56e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE---EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd08218   5 IKKIGEGSFGKALLVKSKEDGKqYVIKEINISKMSPKEREEsrkEVAVLSKMKHPNIVQYQESFEENGNLYIVMDYCDGG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST--GT 518
Cdd:cd08218  85 DLYKRINAQRGvLFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTVELARTciGT 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 KFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKER 598
Cdd:cd08218 165 PY---YLSPEICENKPYNNKSDIWALGCVLYEMCTL-KHAFEAGNMKNLVLKIIRGSYPPVPSRYSYDLRSLVSQLFKRN 240
                       250
                ....*....|...
gi 15718680 599 PEDRPAFSRLLRQ 611
Cdd:cd08218 241 PRDRPSINSILEK 253
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
359-611 1.45e-20

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: 91.53  E-value: 1.45e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPS-ELTFVQEIGSGQFGLVHLGYWLNKD-KVAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd06647   4 DPKkKYTRFEKIGQGASGTVYTAIDVATGqEVAIKQMNlQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVM 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLR---TQRGLFAAetllgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd06647  84 EYLAGGSLTDVVTetcMDEGQIAA-----VCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQS 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSST--GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTGFR--LYKPRLASTHVY 588
Cdd:cd06647 159 KRSTmvGTPY---WMAPEVVTRKAYGPKVDIWSLGIMAIEMV-EGEPPYLNENPLRALYLIATNGTpeLQNPEKLSAIFR 234
                       250       260
                ....*....|....*....|...
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06647 235 DFLNRCLEMDVEKRGSAKELLQH 257
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
364-550 1.56e-20

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: 92.16  E-value: 1.56e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIReGAMSEEDF----IEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFM 438
Cdd:cd07829   2 EKLEKLGEGTYGVVYKAKDKKTGEiVALKKIR-LDNEEEGIpstaLREISLLKELKHPNIVKLLDVIHTENKLYLVFEYC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVlddqytsstgt 518
Cdd:cd07829  81 DQD-LKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAF----------- 148
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 15718680 519 KFPVKWASPEV-----------FSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd07829 149 GIPLRTYTHEVvtlwyrapeilLGSKHYSTAVDIWSVGCIFAE 191
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
369-612 1.63e-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: 1.63e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVhlgyWLNKDKV-----AIKTIR--EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd13996  14 LGSGGFGSV----YKVRNKVdgvtyAIKKIRltEKSSASEKVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEGG 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGLFAAETLLgmCLD----VCEGMAYLEEACVIHRDLAARNCLV-GENQVIKVSDFGMTRFV--------- 507
Cdd:cd13996  90 TLRDWIDRRNSSSKNDRKL--ALElfkqILKGVSYIHSKGIVHRDLKPSNIFLdNDDLQVKIGDFGLATSIgnqkrelnn 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 508 -------LDDQYTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYEnRSNsevvedISTGFRLYK- 579
Cdd:cd13996 168 lnnnnngNTSNNSVGIGTPL---YASPEQLDGENYNEKADIYSLGIILFEMLHPFKTAME-RST------ILTDLRNGIl 237
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 15718680 580 -PRLASTH--VYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd13996 238 pESFKAKHpkEADLIQSLLSKNPEERPSAEQLLRSL 273
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
369-550 2.80e-20

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: 91.62  E-value: 2.80e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKT---------IREGAMSEEDFIEEAEvmmklSHPKLVQLYGVCLEQAPICLVFEFM 438
Cdd:cd07832   8 IGEGAHGIVFKAKDRETGEtVALKKvalrkleggIPNQALREIKALQACQ-----GHPYVVKLRDVFPHGTGFVLVFEYM 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGcLSDYLR-TQRGLFAAET--LLGMCLdvcEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD---QY 512
Cdd:cd07832  83 LSS-LSEVLRdEERPLTEAQVkrYMRMLL---KGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEdprLY 158
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 15718680 513 TSSTGTKFpvkWASPEVFSFSR-YSSKSDVWSFGVLMWE 550
Cdd:cd07832 159 SHQVATRW---YRAPELLYGSRkYDEGVDLWAVGCIFAE 194
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
369-609 3.20e-20

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: 90.69  E-value: 3.20e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKD-KVAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14186   9 LGKGSFACVYRARSLHTGlEVAIKMIDKKAMQKAGMVQrvrnEVEIHCQLKHPSILELYNYFEDSNYVYLVLEMCHNGEM 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM-TRFVL-DDQYTSSTGTKfp 521
Cdd:cd14186  89 SRYLKNRKKPFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLaTQLKMpHEKHFTMCGTP-- 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 522 vKWASPEVFSFSRYSSKSDVWSFGVlMWEVFSEGKIPYE-----NRSNSEVVEDISTgfrlykPRLASTHVYQIMNHCWK 596
Cdd:cd14186 167 -NYISPEIATRSAHGLESDVWSLGC-MFYTLLVGRPPFDtdtvkNTLNKVVLADYEM------PAFLSREAQDLIHQLLR 238
                       250
                ....*....|...
gi 15718680 597 ERPEDRPAFSRLL 609
Cdd:cd14186 239 KNPADRLSLSSVL 251
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
362-609 3.60e-20

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: 90.95  E-value: 3.60e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVhlgywlnkDK---------VAIKTIREGAMSEED--FIEEAEVMMKLSH-PKLVQLYGVCLEQA 429
Cdd:cd06617   2 DLEVIEELGRGAYGVV--------DKmrhvptgtiMAVKRIRATVNSQEQkrLLMDLDISMRSVDcPYTVTFYGALFREG 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEhGCLSDYLRT--QRGLFAAETLLG-MCLDVCEGMAYLEEAC-VIHRDLAARNCLVGENQVIKVSDFGMTR 505
Cdd:cd06617  74 DVWICMEVMD-TSLDKFYKKvyDKGLTIPEDILGkIAVSIVKALEYLHSKLsVIHRDVKPSNVLINRNGQVKLCDFGISG 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 FVLDD-QYTSSTGTKfpvKWASPEVF----SFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSN-----SEVVEDIStgf 575
Cdd:cd06617 153 YLVDSvAKTIDAGCK---PYMAPERInpelNQKGYDVKSDVWSLGITMIEL-ATGRFPYDSWKTpfqqlKQVVEEPS--- 225
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 15718680 576 rlykPRLA----STHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd06617 226 ----PQLPaekfSPEFQDFVNKCLKKNYKERPNYPELL 259
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
367-579 3.93e-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: 90.62  E-value: 3.93e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKD------KVAIKTIREGAMSEED----FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFE 436
Cdd:cd14076   7 RTLGEGEFGKVKLGWPLPKAnhrsgvQVAIKLIRRDTQQENCqtskIMREINILKGLTHPNIVRLLDVLKTKKYIGIVLE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGCLSDYLRTQRGL--FAAETLLGMCLdvcEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM-TRFVLDDQYT 513
Cdd:cd14076  87 FVSGGELFDYILARRRLkdSVACRLFAQLI---SGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFaNTFDHFNGDL 163
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 514 SSTGTKFPVkWASPE-VFSFSRYS-SKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDIStgfRLYK 579
Cdd:cd14076 164 MSTSCGSPC-YAAPElVVSDSMYAgRKADIWSCGVILYAMLA-GYLPFDDDPHNPNGDNVP---RLYR 226
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
369-576 5.70e-20

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: 89.63  E-value: 5.70e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGY-WLNKDKVAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14079  10 LGVGSFGKVKLAEhELTGHKVAVKILNRQKIKSLDMEEkirrEIQILKLFRHPHIIRLYEVIETPTDIFMVMEYVSGGEL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY-TSSTGTkfPv 522
Cdd:cd14079  90 FDYI-VQKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLSNIMRDGEFlKTSCGS--P- 165
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15718680 523 KWASPEVFSFSRYS-SKSDVWSFGVLMWeVFSEGKIPYENrsnsevvEDISTGFR 576
Cdd:cd14079 166 NYAAPEVISGKLYAgPEVDVWSCGVILY-ALLCGSLPFDD-------EHIPNLFK 212
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
361-550 6.26e-20

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: 90.33  E-value: 6.26e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTiregaMSEEDFIE---------EAEVMMKLSHPKLVQLYGVCLEQAP 430
Cdd:cd05580   1 DDFEFLKTLGTGSFGRVRLVKHKDSGKyYALKI-----LKKAKIIKlkqvehvlnEKRILSEVRHPFIVNLLGSFQDDRN 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGCLSDYLRtQRGLF--------AAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFG 502
Cdd:cd05580  76 LYMVMEYVPGGELFSLLR-RSGRFpndvakfyAAEVVLAL--------EYLHSLDIVYRDLKPENLLLDSDGHIKITDFG 146
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 15718680 503 MTRFVLDDQYTsSTGTkfPvKWASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd05580 147 FAKRVKDRTYT-LCGT--P-EYLAPEIILSKGHGKAVDWWALGILIYE 190
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
359-611 6.66e-20

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: 90.55  E-value: 6.66e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSE-LTFVQEIGSGQFGLVHLGYWLN-KDKVAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd06655  16 DPKKkYTRYEKIGQGASGTVFTAIDVAtGQEVAIKQINlQKQPKKELIINEILVMKELKNPNIVNFLDSFLVGDELFVVM 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLrTQRGLFAAEtLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd06655  96 EYLAGGSLTDVV-TETCMDEAQ-IAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQSKRS 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 TGTKFPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTGF--RLYKPRLASTHVYQIMNH 593
Cdd:cd06655 174 TMVGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMV-EGEPPYLNENPLRALYLIATNGtpELQNPEKLSPIFRDFLNR 251
                       250
                ....*....|....*...
gi 15718680 594 CWKERPEDRPAFSRLLRQ 611
Cdd:cd06655 252 CLEMDVEKRGSAKELLQH 269
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
358-609 8.02e-20

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: 90.09  E-value: 8.02e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSEL-TFVQEIGSGQFGLVHLGYwlNKDK---VAIKTIREGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPIC 432
Cdd:cd06644   8 LDPNEVwEIIGELGDGAFGKVYKAK--NKETgalAAAKVIETKSEEElEDYMVEIEILATCNHPYIVKLLGAFYWDGKLW 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCL-SDYLRTQRGLFAAETLLgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD-- 509
Cdd:cd06644  86 IMIEFCPGGAVdAIMLELDRGLTEPQIQV-ICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSAKNVKtl 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGTKFpvkWASPEV-----FSFSRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDI--STGFRLYKPRL 582
Cdd:cd06644 165 QRRDSFIGTPY---WMAPEVvmcetMKDTPYDYKADIWSLGITLIEM-AQIEPPHHELNPMRVLLKIakSEPPTLSQPSK 240
                       250       260
                ....*....|....*....|....*..
gi 15718680 583 ASTHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd06644 241 WSMEFRDFLKTALDKHPETRPSAAQLL 267
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
368-549 8.24e-20

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: 89.32  E-value: 8.24e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYW-LNKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14075   9 ELGSGNFSQVKLGIHqLTKEKVAIKILDKTKLDQKTqrlLSREISSMEKLHHPNIIRLYEVVETLSKLHLVMEYASGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLrTQRGLFA---AETLLGmclDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQyTSSTGTKF 520
Cdd:cd14075  89 YTKI-STEGKLSeseAKPLFA---QIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFSTHAKRGE-TLNTFCGS 163
                       170       180       190
                ....*....|....*....|....*....|
gi 15718680 521 PvKWASPEVFSFSRYSSKS-DVWSFGVLMW 549
Cdd:cd14075 164 P-PYAAPELFKDEHYIGIYvDIWALGVLLY 192
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
369-605 8.47e-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: 89.68  E-value: 8.47e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKD--KVAIKTIREG--AMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14202  10 IGHGAFAVVFKGRHKEKHdlEVAVKCINKKnlAKSQTLLGKEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGGDLA 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVG---------ENQVIKVSDFGMTRFvLDDQYTSS 515
Cdd:cd14202  90 DYLHTMRTL-SEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSysggrksnpNNIRIKIADFGFARY-LQNNMMAA 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 TGTKFPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYK--PRLASTHVYQIMNH 593
Cdd:cd14202 168 TLCGSPM-YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPFQASSPQDLRLFYEKNKSLSPniPRETSSHLRQLLLG 245
                       250
                ....*....|..
gi 15718680 594 CWKERPEDRPAF 605
Cdd:cd14202 246 LLQRNQKDRMDF 257
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
362-616 8.50e-20

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: 89.98  E-value: 8.50e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWlnKDKVAIKTIR----EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd14026   1 DLRYLSRGAFGTVSRARHADW--RVTVAIKCLKldspVGDSERNCLLKEAEILHKARFSYILPILGICNEPEFLGIVTEY 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYL--RTQRGLFAAETLLGMCLDVCEGMAYLEEAC--VIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd14026  79 MTNGSLNELLheKDIYPDVAWPLRLRILYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSKWRQLSISQ 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTGTKFP----VKWASPEVFSFS---RYSSKSDVWSFGVLMWEVFSEgKIPYENRSNS-EVVEDISTGFRlykPRLAST 585
Cdd:cd14026 159 SRSSKSAPeggtIIYMPPEEYEPSqkrRASVKHDIYSYAIIMWEVLSR-KIPFEEVTNPlQIMYSVSQGHR---PDTGED 234
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 15718680 586 H----------VYQIMNHCWKERPEDRPAFSR-------LLRQLAEIA 616
Cdd:cd14026 235 SlpvdiphratLINLIESGWAQNPDERPSFLKclielepVLRTFDEID 282
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
367-606 9.98e-20

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: 89.48  E-value: 9.98e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVH---LGYWlnKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEqaPICLVFEFMEH 440
Cdd:cd14025   2 EKVGSGGFGQVYkvrHKHW--KTWLAIKCPPSLHVDDSErmeLLEEAKKMEMAKFRHILPVYGICSE--PVGLVMEYMET 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDylrtqrgLFAAETL-----LGMCLDVCEGMAYLE--EACVIHRDLAARNCLVGENQVIKVSDFGMTRF--VLDDQ 511
Cdd:cd14025  78 GSLEK-------LLASEPLpwelrFRIIHETAVGMNFLHcmKPPLLHLDLKPANILLDAHYHVKISDFGLAKWngLSHSH 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFPVKWASPEVFSFSR--YSSKSDVWSFGVLMWEVFSEGKiPYENRSN-SEVVEDISTGFRlykPRL------ 582
Cdd:cd14025 151 DLSRDGLRGTIAYLPPERFKEKNrcPDTKHDVYSFAIVIWGILTQKK-PFAGENNiLHIMVKVVKGHR---PSLspiprq 226
                       250       260
                ....*....|....*....|....*..
gi 15718680 583 ---ASTHVYQIMNHCWKERPEDRPAFS 606
Cdd:cd14025 227 rpsECQQMICLMKRCWDQDPRKRPTFQ 253
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
366-553 1.02e-19

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: 89.93  E-value: 1.02e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGywLNK---DKVAIKTIRegaMSEED------FIEEAEVMMKLSHPKLVQLYGVCLEQAP------ 430
Cdd:cd07840   4 IAQIGEGTYGQVYKA--RNKktgELVALKKIR---MENEKegfpitAIREIKLLQKLDHPNVVRLKEIVTSKGSakykgs 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD 510
Cdd:cd07840  79 IYMVFEYMDHD-LTGLLDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYTKE 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 15718680 511 Q---YTSSTGTkfpvKW-ASPEV-FSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd07840 158 NnadYTNRVIT----LWyRPPELlLGATRYGPEVDMWSVGCILAELFT 201
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
369-611 1.20e-19

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: 88.93  E-value: 1.20e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE------EAEVMMKLSHPKLVQLYGvCL---EQAPICLVFEFM 438
Cdd:cd06653  10 LGRGAFGEVYLCYDADTGReLAVKQVPFDPDSQETSKEvnalecEIQLLKNLRHDRIVQYYG-CLrdpEEKKLSIFVEYM 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVlDDQYTSSTGT 518
Cdd:cd06653  89 PGGSVKDQLKAY-GALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRI-QTICMSGTGI 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 KFPVK---WASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTgfRLYKPRL---ASTHVYQIMN 592
Cdd:cd06653 167 KSVTGtpyWMSPEVISGEGYGRKADVWSVACTVVEMLTE-KPPWAEYEAMAAIFKIAT--QPTKPQLpdgVSDACRDFLR 243
                       250
                ....*....|....*....
gi 15718680 593 HCWKERpEDRPAFSRLLRQ 611
Cdd:cd06653 244 QIFVEE-KRRPTAEFLLRH 261
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
369-546 1.42e-19

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: 88.44  E-value: 1.42e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGywlnKDKV-----AIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd14103   1 LGRGKFGTVYRC----VEKAtgkelAAKFIKcRKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 L------SDYLRTQRglfaaETLLGMClDVCEGMAYLEEACVIHRDLAARN--CLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd14103  77 LfervvdDDFELTER-----DCILFMR-QICEGVQYMHKQGILHLDLKPENilCVSRTGNQIKIIDFGLARKYDPDKKLK 150
                       170       180       190
                ....*....|....*....|....*....|...
gi 15718680 515 -STGTkfPvKWASPEVFSFSRYSSKSDVWSFGV 546
Cdd:cd14103 151 vLFGT--P-EFVAPEVVNYEPISYATDMWSVGV 180
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
369-571 1.48e-19

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: 88.50  E-value: 1.48e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYW--LNKDKVAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14121   3 LGSGTYATVYKAYRksGAREVVAVKCVSKSSLNKastENLLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLfaAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLV--GENQVIKVSDFGMTRFV-LDDQYTSSTGTk 519
Cdd:cd14121  83 SRFIRSRRTL--PESTVRRFLqQLASALQFLREHNISHMDLKPQNLLLssRYNPVLKLADFGFAQHLkPNDEAHSLRGS- 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 15718680 520 fPVKWAsPEVFSFSRYSSKSDVWSFGVLMWE-VFseGKIPYENRSNSEVVEDI 571
Cdd:cd14121 160 -PLYMA-PEMILKKKYDARVDLWSVGVILYEcLF--GRAPFASRSFEELEEKI 208
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
369-571 1.50e-19

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: 88.34  E-value: 1.50e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd05123   1 LGKGSFGKVLLVRKKDTGKLyAMKVLRKKEIIKRKEVEhtlnERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVPGGEL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGL-------FAAETLLGmcLDvcegmaYLEEACVIHRDLAARNCLVGENQVIKVSDFGM-TRFVLDDQYTSS 515
Cdd:cd05123  81 FSHLSKEGRFpeerarfYAAEIVLA--LE------YLHSLGIIYRDLKPENILLDSDGHIKLTDFGLaKELSSDGDRTYT 152
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 516 -TGTKFPVkwaSPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05123 153 fCGTPEYL---APEVLLGKGYGKAVDWWSLGVLLYEMLT-GKPPFYAENRKEIYEKI 205
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
369-574 1.69e-19

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: 88.47  E-value: 1.69e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHL-GYWLNKDKVAIKTIREGAM-SEEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 445
Cdd:cd14185   8 IGDGNFAVVKEcRHWNENQEYAMKIIDKSKLkGKEDMIEsEILIIKSLSHPNIVKLFEVYETEKEIYLILEYVRGGDLFD 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ----VIKVSDFGMTRFVLDDQYTsSTGTKfp 521
Cdd:cd14185  88 AI-IESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQHNPdkstTLKLADFGLAKYVTGPIFT-VCGTP-- 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15718680 522 vKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPY--ENRSNSEVVEDISTG 574
Cdd:cd14185 164 -TYVAPEILSEKGYGLEVDMWAAGVILYILLC-GFPPFrsPERDQEELFQIIQLG 216
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
366-553 1.82e-19

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: 88.87  E-value: 1.82e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIRegaMSEED------FIEEAEVMMKL---SHPKLVQLYGVCL-----EQAP 430
Cdd:cd07838   4 VAEIGEGAYGTVYKARDLQDGRfVALKKVR---VPLSEegiplsTIREIALLKQLesfEHPNVVRLLDVCHgprtdRELK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGcLSDYLR--TQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVL 508
Cdd:cd07838  81 LTLVFEHVDQD-LATYLDkcPKPGL-PPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLAR-IY 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 15718680 509 DDQ--YTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd07838 158 SFEmaLTSVVVTLW---YRAPEVLLQSSYATPVDMWSVGCIFAELFN 201
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
369-609 2.36e-19

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: 88.13  E-value: 2.36e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIR----EGAMSEEdFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd06626   8 IGEGTFGKVYTAVNLDTGELmAMKEIRfqdnDPKTIKE-IADEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEGTL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLfaAETLLGM-CLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT-------SS 515
Cdd:cd06626  87 EELLRHGRIL--DEAVIRVyTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLKNNTTTmapgevnSL 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 TGTkfPVKWAsPEVFSFSRYSSK---SDVWSFGVLMWEVFSeGKIP-YENRSNSEVVEDISTGfrlYKPRL-----ASTH 586
Cdd:cd06626 165 VGT--PAYMA-PEVITGNKGEGHgraADIWSLGCVVLEMAT-GKRPwSELDNEWAIMYHVGMG---HKPPIpdslqLSPE 237
                       250       260
                ....*....|....*....|...
gi 15718680 587 VYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd06626 238 GKDFLSRCLESDPKKRPTASELL 260
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
367-551 2.65e-19

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: 88.16  E-value: 2.65e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGY-WLNKDKVAIKTIR----EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd08228   8 KKIGRGQFSEVYRATcLLDRKPVALKKVQifemMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLELADAG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSD---YLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT--SST 516
Cdd:cd08228  88 DLSQmikYFKKQKRLIPERTVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTAahSLV 167
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15718680 517 GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEV 551
Cdd:cd08228 168 GTPY---YMSPERIHENGYNFKSDIWSLGCLLYEM 199
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
365-574 3.44e-19

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: 87.58  E-value: 3.44e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLG-YWLNKDKVAIKTIREGAM---SEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd14072   4 LLKTIGKGNFAKVKLArHVLTGREVAIKIIDKTQLnpsSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYASG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQRGLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTrfvldDQYTSstGTKF 520
Cdd:cd14072  84 GEVFDYLVAHGRMKEKEARAKF-RQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFS-----NEFTP--GNKL 155
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 PV-----KWASPEVFSFSRYSS-KSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd14072 156 DTfcgspPYAAPELFQGKKYDGpEVDVWSLGVILYTLVS-GSLPFDGQNLKELRERVLRG 214
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
369-559 5.66e-19

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: 86.92  E-value: 5.66e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEhGCLS 444
Cdd:cd14002   9 IGEGSFGKVYKGRRKYTGQvVALKFIPKRGKSEKElrnLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEYAQ-GELF 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR------FVLddqyTSSTGT 518
Cdd:cd14002  88 QILEDDGTL-PEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARamscntLVL----TSIKGT 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 15718680 519 kfPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPY 559
Cdd:cd14002 163 --PL-YMAPELVQEQPYDHTADLWSLGCILYELFV-GQPPF 199
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
367-603 5.81e-19

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: 87.78  E-value: 5.81e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLG-YWLNKDKVAIKTIR----EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd08229  30 KKIGRGQFSEVYRAtCLLDGVPVALKKVQifdlMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELADAG 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLR---TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGT 518
Cdd:cd08229 110 DLSRMIKhfkKQKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTAAHSLV 189
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 KFPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSN-SEVVEDIStgfRLYKPRLASTH----VYQIMNH 593
Cdd:cd08229 190 GTPY-YMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGDKMNlYSLCKKIE---QCDYPPLPSDHyseeLRQLVNM 265
                       250
                ....*....|
gi 15718680 594 CWKERPEDRP 603
Cdd:cd08229 266 CINPDPEKRP 275
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
365-553 6.58e-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. 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: 87.37  E-value: 6.58e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVhlgyWLNKDK-----VAIK---TIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFE 436
Cdd:cd07833   5 VLGVVGEGAYGVV----LKCRNKatgeiVAIKkfkESEDDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGCLSDYLRTQRGLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL---DDQYT 513
Cdd:cd07833  81 YVERTLLELLEASPGGLPPDAVRSYI-WQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTarpASPLT 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 15718680 514 SSTGTKFpvkWASPEVF-SFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd07833 160 DYVATRW---YRAPELLvGDTNYGKPVDVWAIGCIMAELLD 197
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
357-617 6.74e-19

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: 87.47  E-value: 6.74e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSE-LTFVQEIGSGQFGLVHLGYWL-NKDKVAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICL 433
Cdd:cd06654  15 VGDPKKkYTRFEKIGQGASGTVYTAMDVaTGQEVAIRQMNlQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWV 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLR---TQRGLFAAetllgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD 510
Cdd:cd06654  95 VMEYLAGGSLTDVVTetcMDEGQIAA-----VCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPE 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 QYTSSTGTKFPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTGF--RLYKPRLASTHVY 588
Cdd:cd06654 170 QSKRSTMVGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMI-EGEPPYLNENPLRALYLIATNGtpELQNPEKLSAIFR 247
                       250       260       270
                ....*....|....*....|....*....|
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLR-QLAEIAE 617
Cdd:cd06654 248 DFLNRCLEMDVEKRGSAKELLQhQFLKIAK 277
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
369-574 7.68e-19

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: 86.51  E-value: 7.68e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKD-KVAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDY 446
Cdd:cd14190  12 LGGGKFGKVHTCTEKRTGlKLAAKVINkQNSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFMEYVEGGELFER 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 447 LRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN--CLVGENQVIKVSDFGMT-RFVLDDQYTSSTGTKfpvK 523
Cdd:cd14190  92 IVDEDYHLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENilCVNRTGHQVKIIDFGLArRYNPREKLKVNFGTP---E 168
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 524 WASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd14190 169 FLSPEVVNYDQVSFPTDMWSMGVITYMLLS-GLSPFLGDDDTETLNNVLMG 218
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
369-610 8.06e-19

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: 86.69  E-value: 8.06e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWL-NKDKVAIKTIREGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCLEQApICLVFefMEH---GCL 443
Cdd:cd06624  16 LGKGTFGVVYAARDLsTQVRIAIKEIPERDSREvQPLHEEIALHSRLSHKNIVQYLGSVSEDG-FFKIF--MEQvpgGSL 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRG-LFAAETLLGM-CLDVCEGMAYLEEACVIHRDLAARNCLVGE-NQVIKVSDFGMTRFV--LDDQYTSSTGT 518
Cdd:cd06624  93 SALLRSKWGpLKDNENTIGYyTKQILEGLKYLHDNKIVHRDIKGDNVLVNTySGVVKISDFGTSKRLagINPCTETFTGT 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 kfpVKWASPEVFSFSR--YSSKSDVWSFGVLMWEVfSEGKIPYenrsnSEVVEDISTGFR--LYK-----PRLASTHVYQ 589
Cdd:cd06624 173 ---LQYMAPEVIDKGQrgYGPPADIWSLGCTIIEM-ATGKPPF-----IELGEPQAAMFKvgMFKihpeiPESLSEEAKS 243
                       250       260
                ....*....|....*....|.
gi 15718680 590 IMNHCWKERPEDRPAFSRLLR 610
Cdd:cd06624 244 FILRCFEPDPDKRATASDLLQ 264
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
409-615 8.63e-19

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: 86.69  E-value: 8.63e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 409 VMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQR----GLFAAETLLgmclDVCEGMAYLEEACVIHRDLA 484
Cdd:cd14043  49 KLRELRHENVNLFLGLFVDCGILAIVSEHCSRGSLEDLLRNDDmkldWMFKSSLLL----DLIKGMRYLHHRGIVHGRLK 124
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 485 ARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFS----FSRYSSKSDVWSFGVLMWEVFSEGKiPY- 559
Cdd:cd14043 125 SRNCVVDGRFVLKITDYGYNEILEAQNLPLPEPAPEELLWTAPELLRdprlERRGTFPGDVFSFAIIMQEVIVRGA-PYc 203
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15718680 560 -ENRSNSEVVEDISTGFRLYKPRL----ASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14043 204 mLGLSPEEIIEKVRSPPPLCRPSVsmdqAPLECIQLMKQCWSEAPERRPTFDQIFDQFKSI 264
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
365-572 9.68e-19

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: 86.89  E-value: 9.68e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGywlnKDK-----VAIKT------IREGAMSEedFIEEAEVMMKLSHPKLVQLYGVCLEQAPICL 433
Cdd:cd05581   5 FGKPLGEGSYSTVVLA----KEKetgkeYAIKVldkrhiIKEKKVKY--VTIEKEVLSRLAHPGIVKLYYTFQDESKLYF 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRTQRGL-------FAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF 506
Cdd:cd05581  79 VLEYAPNGDLLEYIRKYGSLdekctrfYTAEIVLAL--------EYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKV 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 VLDDQYTSSTGTKFPVKWA----------------SPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVED 570
Cdd:cd05581 151 LGPDSSPESTKGDADSQIAynqaraasfvgtaeyvSPELLNEKPAGKSSDLWALGCIIYQMLT-GKPPFRGSNEYLTFQK 229

                ..
gi 15718680 571 IS 572
Cdd:cd05581 230 IV 231
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
360-611 1.26e-18

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: 86.25  E-value: 1.26e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 360 PSELTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE------EAEVMMKLSHPKLVQLYGvCLEQAP-- 430
Cdd:cd06652   1 PTNWRLGKLLGQGAFGRVYLCYDADTGReLAVKQVQFDPESPETSKEvnalecEIQLLKNLLHERIVQYYG-CLRDPQer 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 -ICLVFEFMEHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD 509
Cdd:cd06652  80 tLSIFMEYMPGGSIKDQLKSY-GALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQT 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 -----DQYTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTgfRLYKPRL-- 582
Cdd:cd06652 159 iclsgTGMKSVTGTPY---WMSPEVISGEGYGRKADIWSVGCTVVEMLTE-KPPWAEFEAMAAIFKIAT--QPTNPQLpa 232
                       250       260       270
                ....*....|....*....|....*....|
gi 15718680 583 -ASTHVYQIMNHCWKErPEDRPAFSRLLRQ 611
Cdd:cd06652 233 hVSDHCRDFLKRIFVE-AKLRPSADELLRH 261
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
359-558 1.58e-18

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: 86.21  E-value: 1.58e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL-TFVQEIGSGQFGLVHLGYWLNKDKVA-IKTIREGAMSEEDFIEEAEVMMKLSHPK-LVQLYGVCLEQAP----- 430
Cdd:cd06636  13 DPAGIfELVEVVGNGTYGQVYKGRHVKTGQLAaIKVMDVTEDEEEEIKLEINMLKKYSHHRnIATYYGAFIKKSPpghdd 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 -ICLVFEFMEHGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVL 508
Cdd:cd06636  93 qLWLVMEFCGAGSVTDLVKNTKGnALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSA-QL 171
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 509 D---DQYTSSTGTKFpvkWASPEVFSF-----SRYSSKSDVWSFGVLMWEVfSEGKIP 558
Cdd:cd06636 172 DrtvGRRNTFIGTPY---WMAPEVIACdenpdATYDYRSDIWSLGITAIEM-AEGAPP 225
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
369-563 1.63e-18

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: 85.83  E-value: 1.63e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKD--KVAIKTIREGAMSEEDFI--EEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14201  14 VGHGAFAVVFKGRHRKKTdwEVAIKSINKKNLSKSQILlgKEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNGGDLA 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTqRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVG---------ENQVIKVSDFGMTRFvLDDQYTSS 515
Cdd:cd14201  94 DYLQA-KGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSyasrkkssvSGIRIKIADFGFARY-LQSNMMAA 171
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 15718680 516 TGTKFPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRS 563
Cdd:cd14201 172 TLCGSPM-YMAPEVIMSQHYDAKADLWSIGTVIYQCLV-GKPPFQANS 217
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
367-550 1.66e-18

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: 85.79  E-value: 1.66e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSE----EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd08224   6 KKIGKGQFSVVYRARCLLDGRlVALKKVQIFEMMDakarQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLELADAG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLS---DYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFvlddqYTSST-- 516
Cdd:cd08224  86 DLSrliKHFKKQKRLIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRF-----FSSKTta 160
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 15718680 517 -----GTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd08224 161 ahslvGTPY---YMSPERIREQGYDFKSDIWSLGCLLYE 196
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
406-547 1.78e-18

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: 85.49  E-value: 1.78e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 406 EAEVMMKLSHPKLVQLYGVCLEQAP------ICLVFEFMEHGCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVI 479
Cdd:cd14012  48 ELESLKKLRHPNLVSYLAFSIERRGrsdgwkVYLLTEYAPGGSLSELL-DSVGSVPLDTARRWTLQLLEALEYLHRNGVV 126
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680 480 HRDLAARNCLVGENQ---VIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFS-RYSSKSDVWSFGVL 547
Cdd:cd14012 127 HKSLHAGNVLLDRDAgtgIVKLTDYSLGKTLLDMCSRGSLDEFKQTYWLPPELAQGSkSPTRKTDVWDLGLL 198
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
357-611 2.19e-18

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: 85.93  E-value: 2.19e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSE-LTFVQEIGSGQFGLVHLGYWL-NKDKVAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICL 433
Cdd:cd06656  14 VGDPKKkYTRFEKIGQGASGTVYTAIDIaTGQEVAIKQMNlQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWV 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLR---TQRGLFAAetllgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD 510
Cdd:cd06656  94 VMEYLAGGSLTDVVTetcMDEGQIAA-----VCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPE 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 QYTSSTGTKFPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTGF--RLYKPRLASTHVY 588
Cdd:cd06656 169 QSKRSTMVGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMV-EGEPPYLNENPLRALYLIATNGtpELQNPERLSAVFR 246
                       250       260
                ....*....|....*....|...
gi 15718680 589 QIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06656 247 DFLNRCLEMDVDRRGSAKELLQH 269
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
362-609 2.60e-18

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: 85.55  E-value: 2.60e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIR--EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP--ICLVFE 436
Cdd:cd06621   2 KIVELSSLGEGAGGSVTKCRLRNTKTIfALKTITtdPNPDVQKQILRELEINKSCASPYIVKYYGAFLDEQDssIGIAME 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGCL-SDY--LRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd06621  82 YCEGGSLdSIYkkVKKKGGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSGELVNSLAG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYE-----------------NRSNSEVVEDISTGFR 576
Cdd:cd06621 162 TFTGTSY---YMAPERIQGGPYSITSDVWSLGLTLLEV-AQNRFPFPpegepplgpiellsyivNMPNPELKDEPENGIK 237
                       250       260       270
                ....*....|....*....|....*....|...
gi 15718680 577 LYKPrlasthVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd06621 238 WSES------FKDFIEKCLEKDGTRRPGPWQML 264
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
359-586 2.69e-18

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: 85.86  E-value: 2.69e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSE-LTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd06658  19 DPREyLDSFIKIGEGSTGIVCIATEKHTGKqVAVKKMDlRKQQRRELLFNEVVIMRDYHHENVVDMYNSYLVGDELWVVM 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD--QYT 513
Cdd:cd06658  99 EFLEGGALTDIVTHTR--MNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEvpKRK 176
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 514 SSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTGFrlyKPRLASTH 586
Cdd:cd06658 177 SLVGTPY---WMAPEVISRLPYGTEVDIWSLGIMVIEMI-DGEPPYFNEPPLQAMRRIRDNL---PPRVKDSH 242
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
367-617 2.99e-18

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: 84.85  E-value: 2.99e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHL-GYWLNKDKVAIKTIREGAMSE-EDFIEEAEVMMKLS-HPKLVQLYGVCLEQA-------PICLVFE 436
Cdd:cd13975   6 RELGRGQYGVVYAcDSWGGHFPCALKSVVPPDDKHwNDLALEFHYTRSLPkHERIVSLHGSVIDYSygggssiAVLLIME 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 fmehgclsdylRTQRGLFAA-------ETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGmtrFVLD 509
Cdd:cd13975  86 -----------RLHRDLYTGikaglslEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLG---FCKP 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGTKFPVKWAsPEVFSfSRYSSKSDVWSFGVLMWEVFS-EGKIP--YENRSNSEVV-EDISTGFRLYKPRLAST 585
Cdd:cd13975 152 EAMMSGSIVGTPIHMA-PELFS-GKYDNSVDVYAFGILFWYLCAgHVKLPeaFEQCASKDHLwNNVRKGVRPERLPVFDE 229
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 586 HVYQIMNHCWKERPEDRPAFSRLLRQLAEIAE 617
Cdd:cd13975 230 ECWNLMEACWSGDPSQRPLLGIVQPKLQGIMD 261
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
355-611 3.07e-18

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: 85.50  E-value: 3.07e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEED--FIEEAEVMMKlSH--PKLVQLYGVCLEQA 429
Cdd:cd06618   9 KYKADLNDLENLGEIGSGTCGQVYKMRHKKTGHVmAVKQMRRSGNKEENkrILMDLDVVLK-SHdcPYIVKCYGYFITDS 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEhGCLSDYLRTQRGLFAaETLLG-MCLDVCEGMAYL-EEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV 507
Cdd:cd06618  88 DVFICMELMS-TCLDKLLKRIQGPIP-EDILGkMTVSIVKALHYLkEKHGVIHRDVKPSNILLDESGNVKLCDFGISGRL 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 508 LDDQ-YTSSTGTKfpvKWASPEVFS---FSRYSSKSDVWSFGVLMWEVfSEGKIPYEN-RSNSEVVEDIstgFRLYKPRL 582
Cdd:cd06618 166 VDSKaKTRSAGCA---AYMAPERIDppdNPKYDIRADVWSLGISLVEL-ATGQFPYRNcKTEFEVLTKI---LNEEPPSL 238
                       250       260       270
                ....*....|....*....|....*....|....
gi 15718680 583 ASTHVYQIM-----NHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06618 239 PPNEGFSPDfcsfvDLCLTKDHRYRPKYRELLQH 272
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
388-615 3.69e-18

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: 84.91  E-value: 3.69e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 388 VAIKTIREGAMSEEDFI-EEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDV 466
Cdd:cd14045  33 VAIKKIAKKSFTLSKRIrKEVKQVRELDHPNLCKFIGGCIEVPNVAIITEYCPKGSLNDVLLNEDIPLNWGFRFSFATDI 112
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 467 CEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG--TKFPVKWASPEVFSFSRY--SSKSDVW 542
Cdd:cd14045 113 ARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLTTYRKEDGSENASGyqQRLMQVYLPPENHSNTDTepTQATDVY 192
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 543 SFGVLMWEVFSEGKIPYENRSNSEvvedisTGFRLYKPRLAS----------THVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd14045 193 SYAIILLEIATRNDPVPEDDYSLD------EAWCPPLPELISgktenscpcpADYVELIRRCRKNNPAQRPTFEQIKKTL 266

                ...
gi 15718680 613 AEI 615
Cdd:cd14045 267 HKI 269
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
359-611 3.72e-18

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: 85.54  E-value: 3.72e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL-TFVQEIGSGQFGLVHLGYWLNKDKVA-IKTIREGAMSEEDFIEEAEVMMKLSHPK-LVQLYGVCLEQAP----- 430
Cdd:cd06637   3 DPAGIfELVELVGNGTYGQVYKGRHVKTGQLAaIKVMDVTGDEEEEIKQEINMLKKYSHHRnIATYYGAFIKKNPpgmdd 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 -ICLVFEFMEHGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVL 508
Cdd:cd06637  83 qLWLVMEFCGAGSVTDLIKNTKGnTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSA-QL 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 D---DQYTSSTGTKFpvkWASPEVFSF-----SRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDIStgfRLYKP 580
Cdd:cd06637 162 DrtvGRRNTFIGTPY---WMAPEVIACdenpdATYDFKSDLWSLGITAIEM-AEGAPPLCDMHPMRALFLIP---RNPAP 234
                       250       260       270
                ....*....|....*....|....*....|....*
gi 15718680 581 RLAS---THVYQ-IMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06637 235 RLKSkkwSKKFQsFIESCLVKNHSQRPSTEQLMKH 269
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
369-610 6.23e-18

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: 84.45  E-value: 6.23e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYW-LNKDKVAIKTIREGAMSEE--DFIEEAEVMMKLSH---PKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd06917   9 VGRGSYGAVYRGYHvKTGRVVALKVLNLDTDDDDvsDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIMDYCEGGS 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQR------GLFAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST 516
Cdd:cd06917  89 IRTLMRAGPiaeryiAVIMREVLVAL--------KFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSKRST 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 --GTKFpvkWASPEVFSFSR-YSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDIStgfRLYKPRLASTHVYQIMNH 593
Cdd:cd06917 161 fvGTPY---WMAPEVITEGKyYDTKADIWSLGITTYEM-ATGNPPYSDVDALRAVMLIP---KSKPPRLEGNGYSPLLKE 233
                       250       260
                ....*....|....*....|.
gi 15718680 594 ----CWKERPEDRPAFSRLLR 610
Cdd:cd06917 234 fvaaCLDEEPKDRLSADELLK 254
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
369-615 6.90e-18

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: 84.41  E-value: 6.90e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNkDKVAIKTIREGamSEEDFIEEAE----VMMKlsHPKLVQLYG----VCLEQAPICLVFEFMEH 440
Cdd:cd13998   3 IGKGRFGEVWKASLKN-EPVAVKIFSSR--DKQSWFREKEiyrtPMLK--HENILQFIAaderDTALRTELWLVTAFHPN 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRtqRGLFAAETLLGMCLDVCEGMAYLEEACVI---------HRDLAARNCLVGENQVIKVSDFGMT-RF---- 506
Cdd:cd13998  78 GSL*DYLS--LHTIDWVSLCRLALSVARGLAHLHSEIPGctqgkpaiaHRDLKSKNILVKNDGTCCIADFGLAvRLspst 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 -VLDDQYTSSTGTKfpvKWASPEVF----SFSRYSS--KSDVWSFGVLMWEVFS----------EGKIPYENR-SNSEVV 568
Cdd:cd13998 156 gEEDNANNGQVGTK---RYMAPEVLegaiNLRDFESfkRVDIYAMGLVLWEMASrctdlfgiveEYKPPFYSEvPNHPSF 232
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 569 EDISTGFRLYKPR----------LASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd13998 233 EDMQEVVVRDKQRpnipnrwlshPGLQSLAETIEECWDHDAEARLTAQCIEERLSEF 289
SH3_Tec cd11905
Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a ...
175-229 7.78e-18

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec 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. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212838 [Multi-domain]  Cd Length: 56  Bit Score: 77.55  E-value: 7.78e-18
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15718680 175 VVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEK 229
Cdd:cd11905   2 IVVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWWKARDKYGKEGYIPSNYVTGK 56
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
362-571 9.02e-18

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: 84.67  E-value: 9.02e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIEEAEV---MMKLSH--PKLVQLYGVCLEQAPICLVF 435
Cdd:cd05616   1 DFNFLMVLGKGSFGKVMLAERKGTDELyAVKILKKDVVIQDDDVECTMVekrVLALSGkpPFLTQLHSCFQTMDRLYFVM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSdYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd05616  81 EYVNGGDLM-YHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTK 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 516 TGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05616 160 TFCGTP-DYIAPEIIAYQPYGKSVDWWAFGVLLYEMLA-GQAPFEGEDEDELFQSI 213
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
367-609 1.18e-17

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK 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: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 82.92  E-value: 1.18e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDKVA-IKTIRE-GAMSEEDFIEEAEVMMKLSHPKLVQLYGVClEQAP-ICLVFEFMEHGCL 443
Cdd:cd14057   1 TKINETHSGELWKGRWQGNDIVAkILKVRDvTTRISRDFNEEYPRLRIFSHPNVLPVLGAC-NSPPnLVVISQYMPYGSL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAET-LLGMCLDVCEGMAYLE--EACVIHRDLAARNCLVGENQVIKVSdFGMTRFVLDDQytsstGTKF 520
Cdd:cd14057  80 YNVLHEGTGVVVDQSqAVKFALDIARGMAFLHtlEPLIPRHHLNSKHVMIDEDMTARIN-MADVKFSFQEP-----GKMY 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 521 PVKWASPEVFSFS---RYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDIS-TGFRLYKPRLASTHVYQIMNHCWK 596
Cdd:cd14057 154 NPAWMAPEALQKKpedINRRSADMWSFAILLWELVTR-EVPFADLSNMEIGMKIAlEGLRVTIPPGISPHMCKLMKICMN 232
                       250
                ....*....|...
gi 15718680 597 ERPEDRPAFSRLL 609
Cdd:cd14057 233 EDPGKRPKFDMIV 245
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
366-571 1.25e-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: 83.09  E-value: 1.25e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKD-KVAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14192   9 HEVLGGGRFGQVHKCTELSTGlTLAAKIIKvKGAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYVDGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN--CLVGENQVIKVSDFGMTR-FVLDDQYTSSTGTKf 520
Cdd:cd14192  89 FDRITDESYQLTELDAILFTRQICEGVHYLHQHYILHLDLKPENilCVNSTGNQIKIIDFGLARrYKPREKLKVNFGTP- 167
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 521 pvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14192 168 --EFLAPEVVNYDFVSFPTDMWSVGVITYMLLS-GLSPFLGETDAETMNNI 215
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
406-612 1.36e-17

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: 83.41  E-value: 1.36e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 406 EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQR----GLFAAeTLLGmclDVCEGMAYLEEAcVI-- 479
Cdd:cd14042  52 ELKHMRDLQHDNLTRFIGACVDPPNICILTEYCPKGSLQDILENEDikldWMFRY-SLIH---DIVKGMHYLHDS-EIks 126
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 480 HRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVK-WASPEVF----SFSRYSSKSDVWSFGVLMWEVFS- 553
Cdd:cd14042 127 HGNLKSSNCVVDSRFVLKITDFGLHSFRSGQEPPDDSHAYYAKLlWTAPELLrdpnPPPPGTQKGDVYSFGIILQEIATr 206
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 554 EGkiPY----ENRSNSE-VVEDISTG----FR-LYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd14042 207 QG--PFyeegPDLSPKEiIKKKVRNGekppFRpSLDELECPDEVLSLMQRCWAEDPEERPDFSTLRNKL 273
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
369-559 1.38e-17

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: 83.04  E-value: 1.38e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd05572   1 LGVGGFGRVELVQLKSKGRTfALKCVKKRHIVQTRQQEhifsEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGEL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS-TGTkfPv 522
Cdd:cd05572  81 WTILR-DRGLFDEYTARFYTACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGSGRKTWTfCGT--P- 156
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15718680 523 KWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPY 559
Cdd:cd05572 157 EYVAPEIILNKGYDFSVDYWSLGILLYE-LLTGRPPF 192
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
365-565 1.62e-17

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: 82.69  E-value: 1.62e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVhlgyWL-----NKDKVAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd05578   4 ILRVIGKGSFGKV----CIvqkkdTKKMFAMKYMNKQKCIEKDSVRnvlnELEILQELEHPFLVNLWYSFQDEEDMYMVV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd05578  80 DLLLGGDLRYHL-QQKVKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTDGTLATS 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 516 T-GTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPYENRSNS 565
Cdd:cd05578 159 TsGTK---PYMAPEVFMRAGYSFAVDWWSLGVTAYE-MLRGKRPYEIHSRT 205
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
175-228 1.64e-17

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and 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 (BCR), 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212839 [Multi-domain]  Cd Length: 55  Bit Score: 76.40  E-value: 1.64e-17
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 15718680 175 VVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVE 228
Cdd:cd11906   2 KVVALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRARDKNGREGYIPSNYVTE 55
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
368-610 1.89e-17

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM 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: 270907 [Multi-domain]  Cd Length: 255  Bit Score: 82.28  E-value: 1.89e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYWLNKD-KVAIKTIREGAMSEEDFIEE-----AEVMM-----KLSHPKLVQL---------YGVCLE 427
Cdd:cd14005   7 LLGKGGFGTVYSGVRIRDGlPVAVKFVPKSRVTEWAMINGpvpvpLEIALllkasKPGVPGVIRLldwyerpdgFLLIME 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 428 QAPICL-VFEFM-EHGCLSDylRTQRGLF--AAETLLGMCldvcegmayleEACVIHRDLAARNCLV----GEnqvIKVS 499
Cdd:cd14005  87 RPEPCQdLFDFItERGALSE--NLARIIFrqVVEAVRHCH-----------QRGVLHRDIKDENLLInlrtGE---VKLI 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 500 DFGMTRFVLDDQYTSSTGTKFpvkWASPEVFSFSRYSSKS-DVWSFGVLMWEVFSeGKIPYENRsnsevvEDISTGFRLY 578
Cdd:cd14005 151 DFGCGALLKDSVYTDFDGTRV---YSPPEWIRHGRYHGRPaTVWSLGILLYDMLC-GDIPFEND------EQILRGNVLF 220
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 579 KPRLaSTHVYQIMNHCWKERPEDRPAFSRLLR 610
Cdd:cd14005 221 RPRL-SKECCDLISRCLQFDPSKRPSLEQILS 251
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
352-611 2.50e-17

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: 82.75  E-value: 2.50e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 352 RYGKWVI-----DPSEL-TFVQEIGSGQFGLVHlgYWLNK---DKVAIKTIREGAMSEEDFIEEAEVMMKLS-HPKLVQL 421
Cdd:cd06638   3 LSGKTIIfdsfpDPSDTwEIIETIGKGTYGKVF--KVLNKkngSKAAVKILDPIHDIDEEIEAEYNILKALSdHPNVVKF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 422 YGVCLEQA-----PICLVFEFMEHGCLSDYLR--TQRGLFAAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVGEN 493
Cdd:cd06638  81 YGMYYKKDvkngdQLWLVLELCNGGSVTDLVKgfLKRGERMEEPIIAYILhEALMGLQHLHVNKTIHRDVKGNNILLTTE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 494 QVIKVSDFGMTRFVLDDQY--TSSTGTKFpvkWASPEVFSF-----SRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSE 566
Cdd:cd06638 161 GGVKLVDFGVSAQLTSTRLrrNTSVGTPF---WMAPEVIACeqqldSTYDARCDVWSLGITAIEL-GDGDPPLADLHPMR 236
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 15718680 567 VVEDISTG--FRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06638 237 ALFKIPRNppPTLHQPELWSNEFNDFIRKCLTKDYEKRPTVSDLLQH 283
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
369-559 2.73e-17

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: 82.17  E-value: 2.73e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLG-YWLNKDKVAIKTIREGAMSEEDFI-----EEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd14070  10 LGEGSFAKVREGlHAVTGEKVAIKVIDKKKAKKDSYVtknlrREGRIQQMIRHPNITQLLDILETENSYYLVMELCPGGN 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV----LDDQYTSSTGT 518
Cdd:cd14070  90 LMHRIYDKKRLEEREARRYI-RQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSNCAgilgYSDPFSTQCGS 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 15718680 519 KfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPY 559
Cdd:cd14070 169 P---AYAAPELLARKKYGPKVDVWSIGVNMYAMLT-GTLPF 205
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
369-559 3.70e-17

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: 81.65  E-value: 3.70e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK--VAIKTIREGAMSE-EDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14120   1 IGHGAFAVVFKGRHRKKPDlpVAIKCITKKNLSKsQNLLGkEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGGDLA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLfaAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVGENQ---------VIKVSDFGMTRFvLDDQYTS 514
Cdd:cd14120  81 DYLQAKGTL--SEDTIRVFLqQIAAAMKALHSKGIVHRDLKPQNILLSHNSgrkpspndiRLKIADFGFARF-LQDGMMA 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 15718680 515 STGTKFPVKWAsPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPY 559
Cdd:cd14120 158 ATLCGSPMYMA-PEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPF 200
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
366-571 3.73e-17

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: 81.94  E-value: 3.73e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLV-HLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14113  12 VAELGRGRFSVVkKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQGRLL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGEN---QVIKVSDFGmtrfvlDDQYTSSTGTKFP 521
Cdd:cd14113  92 DYV-VRWGNLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVDQSlskPTIKLADFG------DAVQLNTTYYIHQ 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 15718680 522 V----KWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14113 165 LlgspEFAAPEIILGNPVSLTSDLWSIGVLTYVLLS-GVSPFLDESVEETCLNI 217
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
369-568 4.08e-17

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: 82.18  E-value: 4.08e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDkVAIKTIREGAMSE-----EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14159   1 IGEGGFGCVYQAVMRNTE-YAVKRLKEDSELDwsvvkNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYVYLPNGSL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGL--FAAETLLGMCLDVCEGMAYL--EEACVIHRDLAARNCLVGENQVIKVSDFGMTRFvldDQYTSSTG-- 517
Cdd:cd14159  80 EDRLHCQVSCpcLSWSQRLHVLLGTARAIQYLhsDSPSLIHGDVKSSNILLDAALNPKLGDFGLARF---SRRPKQPGms 156
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 518 --------TKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVV 568
Cdd:cd14159 157 stlartqtVRGTLAYLPEEYVKTGTLSVEIDVYSFGVVLLELLT-GRRAMEVDSCSPTK 214
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
366-567 5.12e-17

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: 82.00  E-value: 5.12e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK--VAIKTIREgAMSEEDF----IEEAEVMMKLS---HPKLVQLYGVCL-----EQAPI 431
Cdd:cd07862   6 VAEIGEGAYGKVFKARDLKNGGrfVALKRVRV-QTGEEGMplstIREVAVLRHLEtfeHPNVVRLFDVCTvsrtdRETKL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGcLSDYL-RTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD 510
Cdd:cd07862  85 TLVFEHVDQD-LTTYLdKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQ 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 511 QYTSSTGTKfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIpyeNRSNSEV 567
Cdd:cd07862 164 MALTSVVVT--LWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPL---FRGSSDV 215
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
369-602 5.21e-17

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: 82.36  E-value: 5.21e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVhlgyWLNKDKV-----AIKTIREGAMSEED----FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd05595   3 LGKGTFGKV----ILVREKAtgryyAMKILRKEVIIAKDevahTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYAN 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTK 519
Cdd:cd05595  79 GGELFFHLSRER-VFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGITDGATMKTFCG 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 520 FPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfRLYKPRLASTHVYQIMNHCWKERP 599
Cdd:cd05595 158 TP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHERLFELILME-EIRFPRTLSPEAKSLLAGLLKKDP 234

                ...
gi 15718680 600 EDR 602
Cdd:cd05595 235 KQR 237
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
365-559 5.61e-17

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: 81.20  E-value: 5.61e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDK-VAIKTIregAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd06613   4 LIQRIGSGTYGDVYKARNIATGElAAVKVI---KLEPGDDFEiiqqEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGLfaAETLLG-MCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfvlddQYTSS--- 515
Cdd:cd06613  81 GGSLQDIYQVTGPL--SELQIAyVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSA-----QLTATiak 153
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 516 ----TGTKFpvkWASPEVFSFSR---YSSKSDVWSFGVLMWEVfSEGKIPY 559
Cdd:cd06613 154 rksfIGTPY---WMAPEVAAVERkggYDGKCDIWALGITAIEL-AELQPPM 200
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
365-575 5.95e-17

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: 81.58  E-value: 5.95e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd14166   7 FMEVLGSGAFSEVYLVKQRSTGKLyALKCIKKSPLSRDSSLEnEIAVLKRIKHENIVTLEDIYESTTHYYLVMQLVSGGE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV---GENQVIKVSDFGMTRfvLDDQYTSSTGTK 519
Cdd:cd14166  87 LFDRI-LERGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLYltpDENSKIMITDFGLSK--MEQNGIMSTACG 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 520 FPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGF 575
Cdd:cd14166 164 TP-GYVAPEVLAQKPYSKAVDCWSIGVITYILLC-GYPPFYEETESRLFEKIKEGY 217
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
359-559 6.67e-17

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: 81.57  E-value: 6.67e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL--TFVQeIGSGQFGLV------HLGywlnkDKVAIKT--IREGAMSEEDFiEEAEVMMKLSHPKLVQLYGVCLEQ 428
Cdd:cd06659  18 DPRQLleNYVK-IGEGSTGVVciarekHSG-----RQVAVKMmdLRKQQRRELLF-NEVVIMRDYQHPNVVEMYKSYLVG 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 429 APICLVFEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL 508
Cdd:cd06659  91 EELWVLMEYLQGGALTDIVSQTR--LNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQIS 168
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 15718680 509 DD--QYTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPY 559
Cdd:cd06659 169 KDvpKRKSLVGTPY---WMAPEVISRCPYGTEVDIWSLGIMVIEMV-DGEPPY 217
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
365-566 6.76e-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: 81.37  E-value: 6.76e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQ--EIGSGQFGLVHLGY-WLNKDKVAIKTIR----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd07836   2 FKQleKLGEGTYATVYKGRnRTTGEIVALKEIHldaeEGTPSTA--IREISLMKELKHENIVRLHDVIHTENKLMLVFEY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEhGCLSDYL--RTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF--VLDDQYT 513
Cdd:cd07836  80 MD-KDLKKYMdtHGVRGALDPNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAfgIPVNTFS 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 15718680 514 SSTGTKFpvkWASPEVFSFSR-YSSKSDVWSFGVLMWEVFSeGKIPYENRSNSE 566
Cdd:cd07836 159 NEVVTLW---YRAPDVLLGSRtYSTSIDIWSVGCIMAEMIT-GRPLFPGTNNED 208
STKc_PIM3 cd14102
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
443-609 7.03e-17

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 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: 271004 [Multi-domain]  Cd Length: 253  Bit Score: 80.77  E-value: 7.03e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVG-ENQVIKVSDFGMTRFVLDDQYTSSTGTKFp 521
Cdd:cd14102  92 LFDFI-TEKGALDEDTARGFFRQVLEAVRHCYSCGVVHRDIKDENLLVDlRTGELKLIDFGSGALLKDTVYTDFDGTRV- 169
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 522 vkWASPEVFSFSRYSSKS-DVWSFGVLMWEVFSeGKIPYENRsnsevvEDISTGfRLYKPRLASTHVYQIMNHCWKERPE 600
Cdd:cd14102 170 --YSPPEWIRYHRYHGRSaTVWSLGVLLYDMVC-GDIPFEQD------EEILRG-RLYFRRRVSPECQQLIKWCLSLRPS 239

                ....*....
gi 15718680 601 DRPAFSRLL 609
Cdd:cd14102 240 DRPTLEQIF 248
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
369-552 8.02e-17

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: 81.64  E-value: 8.02e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWL-NKDKVAIKTIRegaMSEE------DFIEEAEVMMKLSHPKLVQLYGVCLEQA--PICLVFEFME 439
Cdd:cd07845  15 IGEGTYGIVYRARDTtSGEIVALKKVR---MDNErdgipiSSLREITLLLNLRHPNIVELKEVVVGKHldSIFLVMEYCE 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVLDDQYTSSTGTK 519
Cdd:cd07845  92 QD-LASLLDNMPTPFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLAR-TYGLPAKPMTPKV 169
                       170       180       190
                ....*....|....*....|....*....|....
gi 15718680 520 FPVKWASPEV-FSFSRYSSKSDVWSFGVLMWEVF 552
Cdd:cd07845 170 VTLWYRAPELlLGCTTYTTAIDMWAVGCILAELL 203
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
359-612 8.25e-17

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: 80.89  E-value: 8.25e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSELTFVQEIGSGQFGLVHLGYWLNkDKVAIKTIR---EGAMSEEDFIEEAEVMmKLSHPKLVQLYGV--CLEQAPICL 433
Cdd:cd13979   1 DWEPLRLQEPLGSGGFGSVYKATYKG-ETVAVKIVRrrrKNRASRQSFWAELNAA-RLRHENIVRVLAAetGTDFASLGL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 V-FEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTrFVLDDqy 512
Cdd:cd13979  79 IiMEYCGNGTLQQLIYEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCS-VKLGE-- 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKFPV-----KWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIPYEN--------------RSNSEVVEDIST 573
Cdd:cd13979 156 GNEVGTPRSHiggtyTYRAPELLKGERVTPKADIYSFGITLWQM-LTRELPYAGlrqhvlyavvakdlRPDLSGLEDSEF 234
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 15718680 574 GFRLYKprlasthvyqIMNHCWKERPEDRP-AFSRLLRQL 612
Cdd:cd13979 235 GQRLRS----------LISRCWSAQPAERPnADESLLKSL 264
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
365-571 1.16e-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: 80.46  E-value: 1.16e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMS-EEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd14167   7 FREVLGTGAFSEVVLAEEKRTQKlVAIKCIAKKALEgKETSIEnEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVSGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCL---VGENQVIKVSDFGMTRfVLDDQYTSSTGT 518
Cdd:cd14167  87 ELFDRI-VEKGFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSK-IEGSGSVMSTAC 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 15718680 519 KFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14167 165 GTP-GYVAPEVLAQKPYSKAVDCWSIGVIAYILLC-GYPPFYDENDAKLFEQI 215
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
366-602 1.20e-16

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: 80.07  E-value: 1.20e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLN-KDKVAIKTI---REGAMSEEDFIEEAEVMMKLSHPKLVQLYGvCLEQAPICLVF-EFMEH 440
Cdd:cd14069   6 VQTLGEGAFGEVFLAVNRNtEEAVAVKFVdmkRAPGDCPENIKKEVCIQKMLSHKNVVRFYG-HRREGEFQYLFlEYASG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLrtqrglfaaETLLGMCLDVC--------EGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM-TRFVLDDQ 511
Cdd:cd14069  85 GELFDKI---------EPDVGMPEDVAqfyfqqlmAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLaTVFRYKGK 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 ---YTSSTGTkfpVKWASPEVFSFSRY-SSKSDVWSFGVLMWEVFSeGKIPY-ENRSNSEVVEDISTGFRLYK---PRLA 583
Cdd:cd14069 156 erlLNKMCGT---LPYVAPELLAKKKYrAEPVDVWSCGIVLFAMLA-GELPWdQPSDSCQEYSDWKENKKTYLtpwKKID 231
                       250
                ....*....|....*....
gi 15718680 584 STHvYQIMNHCWKERPEDR 602
Cdd:cd14069 232 TAA-LSLLRKILTENPNKR 249
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
369-571 1.37e-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: 79.96  E-value: 1.37e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKD-KVAIKTIREGAMSEEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDY 446
Cdd:cd14193  12 LGGGRFGQVHKCEEKSSGlKLAAKIIKARSQKEKEEVKnEIEVMNQLNHANLIQLYDAFESRNDIVLVMEYVDGGELFDR 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 447 LRTQR-GLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARN--CLVGENQVIKVSDFGMT-RFVLDDQYTSSTGTKfpv 522
Cdd:cd14193  92 IIDENyNLTELDTILFI-KQICEGIQYMHQMYILHLDLKPENilCVSREANQVKIIDFGLArRYKPREKLRVNFGTP--- 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 523 KWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14193 168 EFLAPEVVNYEFVSFPTDMWSLGVIAYMLLS-GLSPFLGEDDNETLNNI 215
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
365-574 1.49e-16

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: 80.18  E-value: 1.49e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLG-YWLNKDKVAIKTI---------------REGAMSEED-FIEEAEVMMKLSHPKLVQLYGVCLE 427
Cdd:cd14077   5 FVKTIGAGSMGKVKLAkHIRTGEKCAIKIIprasnaglkkerekrLEKEISRDIrTIREAALSSLLNHPHICRLRDFLRT 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 428 QAPICLVFEFMEHGCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV 507
Cdd:cd14077  85 PNHYYMLFEYVDGGQLLDYI-ISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNLY 163
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 508 -LDDQYTSSTGTKFpvkWASPEVFSFSRYSS-KSDVWSFGVLMWeVFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd14077 164 dPRRLLRTFCGSLY---FAAPELLQAQPYTGpEVDVWSFGVVLY-VLVCGKVPFDDENMPALHAKIKKG 228
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
369-550 1.64e-16

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: 80.35  E-value: 1.64e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVhlgyWLNKDK-----VAIKTIRegaMSEED--F----IEEAEVMMKLSHPKLVQL----YGVCLEQapICL 433
Cdd:cd07843  13 IEEGTYGVV----YRARDKktgeiVALKKLK---MEKEKegFpitsLREINILLKLQHPNIVTVkevvVGSNLDK--IYM 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD--DQ 511
Cdd:cd07843  84 VMEYVEHD-LKSLMETMKQPFLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAREYGSplKP 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFpvkWASPEV-FSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd07843 163 YTQLVVTLW---YRAPELlLGAKEYSTAIDMWSVGCIFAE 199
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
364-574 1.67e-16

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: 79.68  E-value: 1.67e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLV-HLGYWLNKDKVAIKTI-REGAMSEEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd14095   3 DIGRVIGDGNFAVVkECRDKATDKEYALKIIdKAKCKGKEHMIEnEVAILRRVKHPNIVQLIEEYDTDTELYLVMELVKG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ----VIKVSDFGMTRFVLDDQYTsST 516
Cdd:cd14095  83 GDLFDAI-TSSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVVEHEdgskSLKLADFGLATEVKEPLFT-VC 160
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 517 GTKFPVkwaSPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPY--ENRSNSEVVEDISTG 574
Cdd:cd14095 161 GTPTYV---APEILAETGYGLKVDIWAAGVITYILLC-GFPPFrsPDRDQEELFDLILAG 216
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
369-573 1.80e-16

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: 79.74  E-value: 1.80e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE------EAEVMMKLSHPKLVQLYGvCLE---QAPICLVFEFM 438
Cdd:cd06651  15 LGQGAFGRVYLCYDVDTGReLAAKQVQFDPESPETSKEvsalecEIQLLKNLQHERIVQYYG-CLRdraEKTLTIFMEYM 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQRGLFAAETLlGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD-----DQYT 513
Cdd:cd06651  94 PGGSVKDQLKAYGALTESVTR-KYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTicmsgTGIR 172
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDIST 573
Cdd:cd06651 173 SVTGTPY---WMSPEVISGEGYGRKADVWSLGCTVVEMLTE-KPPWAEYEAMAAIFKIAT 228
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
364-574 1.86e-16

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: 79.90  E-value: 1.86e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYWLNKD-KVAIKTI-REGAMSEEDFIEEAEV--MMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd14097   4 TFGRKLGQGSFGVVIEATHKETQtKWAIKKInREKAGSSAVKLLEREVdiLKHVNHAHIIHLEEVFETPKRMYLVMELCE 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRtQRGLFA-AETLLGMClDVCEGMAYLEEACVIHRDLAARNCLVGENQV-------IKVSDFGM---TRFVL 508
Cdd:cd14097  84 DGELKELLL-RKGFFSeNETRHIIQ-SLASAVAYLHKNDIVHRDLKLENILVKSSIIdnndklnIKVTDFGLsvqKYGLG 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 509 DDQYTSSTGTkfPVkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd14097 162 EDMLQETCGT--PI-YMAPEVISAHGYSQQCDIWSIGVIMYMLLC-GEPPFVAKSEEKLFEEIRKG 223
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
358-611 1.88e-16

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: 80.07  E-value: 1.88e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSEL-TFVQEIGSGQFGLVHLGYwlNKDK---VAIKTIREGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPIC 432
Cdd:cd06643   1 LNPEDFwEIVGELGDGAFGKVYKAQ--NKETgilAAAKVIDTKSEEElEDYMVEIDILASCDHPNIVKLLDAFYYENNLW 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSD-YLRTQRGLFAAETLLgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM----TRFV 507
Cdd:cd06643  79 ILIEFCAGGAVDAvMLELERPLTEPQIRV-VCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVsaknTRTL 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 508 ldDQYTSSTGTKFpvkWASPEVF----SFSR-YSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDI--STGFRLYKP 580
Cdd:cd06643 158 --QRRDSFIGTPY---WMAPEVVmcetSKDRpYDYKADVWSLGVTLIEM-AQIEPPHHELNPMRVLLKIakSEPPTLAQP 231
                       250       260       270
                ....*....|....*....|....*....|.
gi 15718680 581 RLASTHVYQIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd06643 232 SRWSPEFKDFLRKCLEKNVDARWTTSQLLQH 262
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
235-337 1.96e-16

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: 74.73  E-value: 1.96e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 235 ETYEWYNKSISRDKAEkLLLDTGKEGAFMVRDSRTA-GTYTVSVFTKAVVsennpcikhYHIKETNDNPKRYYVAEKYVF 313
Cdd:cd09935   1 EKHSWYHGPISRNAAE-YLLSSGINGSFLVRESESSpGQYSISLRYDGRV---------YHYRISEDSDGKVYVTQEHRF 70
                        90       100
                ....*....|....*....|....
gi 15718680 314 DSIPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd09935  71 NTLAELVHHHSKNADGLITTLRYP 94
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
401-549 2.02e-16

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: 79.71  E-value: 2.02e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 401 EDFIEEAEVMMKLS-HPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMcLDVCEGMAYLEEACVI 479
Cdd:cd14093  53 EATRREIEILRQVSgHPNIIELHDVFESPTFIFLVFELCRKGELFDYLTEVVTLSEKKTRRIM-RQLFEAVEFLHSLNIV 131
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 480 HRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY-TSSTGTKfpvKWASPEVF------SFSRYSSKSDVWSFGVLMW 549
Cdd:cd14093 132 HRDLKPENILLDDNLNVKISDFGFATRLDEGEKlRELCGTP---GYLAPEVLkcsmydNAPGYGKEVDMWACGVIMY 205
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
365-571 2.31e-16

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: 79.34  E-value: 2.31e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGY-WLNKDKVAIKTIREGAMS-EEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd14083   7 FKEVLGTGAFSEVVLAEdKATGKLVAIKCIDKKALKgKEDSLEnEIAVLRKIKHPNIVQLLDIYESKSHLYLVMELVTGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLrTQRGLFA---AETLLGMCLDVCEgmaYLEEACVIHRDLAARNCLV---GENQVIKVSDFGMTRfvLDDQYTSS 515
Cdd:cd14083  87 ELFDRI-VEKGSYTekdASHLIRQVLEAVD---YLHSLGIVHRDLKPENLLYyspDEDSKIMISDFGLSK--MEDSGVMS 160
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 516 TGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14083 161 TACGTP-GYVAPEVLAQKPYGKAVDCWSIGVISYILLC-GYPPFYDENDSKLFAQI 214
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
384-615 2.34e-16

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: 79.54  E-value: 2.34e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 384 NKDKVAIKTIR--EGAMSEEDFIEeAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQ----RGLFAA- 456
Cdd:cd14044  30 DKKVVILKDLKnnEGNFTEKQKIE-LNKLLQIDYYNLTKFYGTVKLDTMIFGVIEYCERGSLRDVLNDKisypDGTFMDw 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 457 ETLLGMCLDVCEGMAYLEEA-CVIHRDLAARNCLVGENQVIKVSDFGMTRFVLddqytsstgtkfPVK--WASPEVFSFS 533
Cdd:cd14044 109 EFKISVMYDIAKGMSYLHSSkTEVHGRLKSTNCVVDSRMVVKITDFGCNSILP------------PSKdlWTAPEHLRQA 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 534 RYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDI-----STGFRLYKPRLA-------STHVYQIMNHCWKERPED 601
Cdd:cd14044 177 GTSQKGDVYSYGIIAQEIILR-KETFYTAACSDRKEKIyrvqnPKGMKPFRPDLNlesagerEREVYGLVKNCWEEDPEK 255
                       250
                ....*....|....
gi 15718680 602 RPAFSRLLRQLAEI 615
Cdd:cd14044 256 RPDFKKIENTLAKI 269
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
362-551 2.57e-16

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: 79.77  E-value: 2.57e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIR-----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd07861   1 DYTKIEKIGEGTYGVVYKGRNKKTGQiVAMKKIRleseeEGVPSTA--IREISLLKELQHPNIVCLEDVLMQENRLYLVF 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGcLSDYLRTQRG--LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF--VLDDQ 511
Cdd:cd07861  79 EFLSMD-LKKYLDSLPKgkYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAfgIPVRV 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 15718680 512 YTSSTGTKFpvkWASPEVFSFS-RYSSKSDVWSFGVLMWEV 551
Cdd:cd07861 158 YTHEVVTLW---YRAPEVLLGSpRYSTPVDIWSIGTIFAEM 195
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
369-603 2.61e-16

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: 79.47  E-value: 2.61e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVhlgYWLNKDK-----VAIKTI-----------REGAMSEEDFIEEAEVM-MKLSHPKLVQLYGVCLEQAPI 431
Cdd:cd08528   8 LGSGAFGCV---YKVRKKSngqtlLALKEInmtnpafgrteQERDKSVGDIISEVNIIkEQLRHPNIVRYYKTFLENDRL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDY---LRTQRGLFAAETLLGMCLDVCEGMAYL-EEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV 507
Cdd:cd08528  85 YIVMELIEGAPLGEHfssLKEKNEHFTEDRIWNIFVQMVLALRYLhKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAKQK 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 508 LDD--QYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEV-------FSEGKIPYENRSNSEVVEDISTGfrly 578
Cdd:cd08528 165 GPEssKMTSVVGT---ILYSCPEIVQNEPYGEKADIWALGCILYQMctlqppfYSTNMLTLATKIVEAEYEPLPEG---- 237
                       250       260
                ....*....|....*....|....*
gi 15718680 579 kprLASTHVYQIMNHCWKERPEDRP 603
Cdd:cd08528 238 ---MYSDDITFVIRSCLTPDPEARP 259
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
366-552 2.80e-16

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: 79.62  E-value: 2.80e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIRegAMSEED-----FIEEAEVMMKLS---HPKLVQLYGVCL-----EQAPI 431
Cdd:cd07863   5 VAEIGVGAYGTVYKARDPHSGHfVALKSVR--VQTNEDglplsTVREVALLKRLEafdHPNIVRLMDVCAtsrtdRETKV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGcLSDYLRT--QRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVld 509
Cdd:cd07863  83 TLVFEHVDQD-LRTYLDKvpPPGL-PAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLARIY-- 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 15718680 510 DQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVF 552
Cdd:cd07863 159 SCQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMF 201
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
364-553 3.01e-16

Catalytic domain of Cyclin-Dependent protein Kinase 8-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 CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. 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 CDK8-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: 270834 [Multi-domain]  Cd Length: 316  Bit Score: 80.02  E-value: 3.01e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYWLN---KDKVAIKTIrEGAMSEEDFIEEA---EVMM--KLSHPKLVQLYGVCLEQAPIC--L 433
Cdd:cd07842   3 EIEGCIGRGTYGRVYKAKRKNgkdGKEYAIKKF-KGDKEQYTGISQSacrEIALlrELKHENVVSLVEVFLEHADKSvyL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEH---GCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV----GENQVIKVSDFGMTRF 506
Cdd:cd07842  82 LFDYAEHdlwQIIKFHRQAKRVSIPPSMVKSLLWQILNGIHYLHSNWVLHRDLKPANILVmgegPERGVVKIGDLGLARL 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 VLDDQYTSSTGTKFPVK-W-ASPEVFSFSR-YSSKSDVWSFGVLMWEVFS 553
Cdd:cd07842 162 FNAPLKPLADLDPVVVTiWyRAPELLLGARhYTKAIDIWAIGCIFAELLT 211
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
357-586 3.04e-16

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 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 protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 79.68  E-value: 3.04e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 357 VIDPSE----LTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP 430
Cdd:cd06657  12 VVDPGDprtyLDNFIKIGEGSTGIVCIATVKSSGKlVAVKKMDlRKQQRRELLFNEVVIMRDYQHENVVEMYNSYLVGDE 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD 510
Cdd:cd06657  92 LWVVMEFLEGGALTDIVTHTR--MNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKE 169
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 511 --QYTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDISTGFrlyKPRLASTH 586
Cdd:cd06657 170 vpRRKSLVGTPY---WMAPELISRLPYGPEVDIWSLGIMVIEMV-DGEPPYFNEPPLKAMKMIRDNL---PPKLKNLH 240
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
365-561 3.06e-16

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: 78.87  E-value: 3.06e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGY-WLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14665   4 LVKDIGSGNFGVARLMRdKQTKELVAVKYIERGEKIDENVQREIINHRSLRHPNIVRFKEVILTPTHLAIVMEYAAGGEL 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQV--IKVSDFGMTR-FVLDDQYTSSTGTKf 520
Cdd:cd14665  84 FERI-CNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAprLKICDFGYSKsSVLHSQPKSTVGTP- 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 15718680 521 pvKWASPEVFSFSRYSSK-SDVWSFGVLMWeVFSEGKIPYEN 561
Cdd:cd14665 162 --AYIAPEVLLKKEYDGKiADVWSCGVTLY-VMLVGAYPFED 200
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
366-550 3.20e-16

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: 79.26  E-value: 3.20e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIR-----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd07835   4 LEKIGEGTYGVVYKARDKLTGEiVALKKIRletedEGVPSTA--IREISLLKELNHPNIVRLLDVVHSENKLYLVFEFLD 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGcLSDYLRTQRGLFAAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR-F-VLDDQYTSST 516
Cdd:cd07835  82 LD-LKKYMDSSPLTGLDPPLIKSYLyQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARaFgVPVRTYTHEV 160
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15718680 517 GTKFpvkWASPEVFSFSR-YSSKSDVWSFGVLMWE 550
Cdd:cd07835 161 VTLW---YRAPEILLGSKhYSTPVDIWSVGCIFAE 192
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
360-609 3.32e-16

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 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: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 78.86  E-value: 3.32e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 360 PSELTFVQEIGSGQFGLVHLGYWLNKdkvaiktiregamsEEDFIeeaevmMKLSHPKLVQLygvcleqapiclVFEFMe 439
Cdd:cd14100  51 PMEIVLLKKVGSGFRGVIRLLDWFER--------------PDSFV------LVLERPEPVQD------------LFDFI- 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 hgclsdylrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ-VIKVSDFGMTRFVLDDQYTSSTGT 518
Cdd:cd14100  98 ---------TERGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENILIDLNTgELKLIDFGSGALLKDTVYTDFDGT 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 KFpvkWASPEVFSFSRYSSKS-DVWSFGVLMWEVFSeGKIPYENRsnsevvEDISTGFRLYKPRLaSTHVYQIMNHCWKE 597
Cdd:cd14100 169 RV---YSPPEWIRFHRYHGRSaAVWSLGILLYDMVC-GDIPFEHD------EEIIRGQVFFRQRV-SSECQHLIKWCLAL 237
                       250
                ....*....|..
gi 15718680 598 RPEDRPAFSRLL 609
Cdd:cd14100 238 RPSDRPSFEDIQ 249
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
369-611 3.34e-16

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: 78.90  E-value: 3.34e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSE----EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14188   9 LGKGGFAKCYEMTDLTTNKVyAAKIIPHSRVSKphqrEKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSM 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV--LDDQYTSSTGTKfp 521
Cdd:cd14188  89 AHILKARKVLTEPEVRYYL-RQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLepLEHRRRTICGTP-- 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 522 vKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfRLYKPRLASTHVYQIMNHCWKERPED 601
Cdd:cd14188 166 -NYLSPEVLNKQGHGCESDIWALGCVMYTMLL-GRPPFETTNLKETYRCIREA-RYSLPSSLLAPAKHLIASMLSKNPED 242
                       250
                ....*....|
gi 15718680 602 RPAFSRLLRQ 611
Cdd:cd14188 243 RPSLDEIIRH 252
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
414-563 3.42e-16

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: 79.92  E-value: 3.42e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 414 SHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV--- 490
Cdd:cd14180  59 SHPNIVALHEVLHDQYHTYLVMELLRGGELLDRIKKKA-RFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYade 137
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 491 GENQVIKVSDFGMTRfvLDDQYTSSTGTK-FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRS 563
Cdd:cd14180 138 SDGAVLKVIDFGFAR--LRPQGSRPLQTPcFTLQYAAPELFSNQGYDESCDLWSLGVILYTMLS-GQVPFQSKR 208
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
402-603 3.54e-16

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: 79.24  E-value: 3.54e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 402 DFIEEAEVMMKLSHPKLVQLYGVCLEqaPICLVFEFMEHGCLSDYLR-TQRGlfAAETLLGMCL------DVCEGMAYLE 474
Cdd:cd14067  56 EFRQEASMLHSLQHPCIVYLIGISIH--PLCFALELAPLGSLNTVLEeNHKG--SSFMPLGHMLtfkiayQIAAGLAYLH 131
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 475 EACVIHRDLAARNCLV-----GENQVIKVSDFGMTRFVLDDQYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMW 549
Cdd:cd14067 132 KKNIIFCDLKSDNILVwsldvQEHINIKLSDYGISRQSFHEGALGVEGTP---GYQAPEIRPRIVYDEKVDMFSYGMVLY 208
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 550 EVFSeGKIPYENRSNSEVVEDISTGFR--LYKPRLASTHVYQ-IMNHCWKERPEDRP 603
Cdd:cd14067 209 ELLS-GQRPSLGHHQLQIAKKLSKGIRpvLGQPEEVQFFRLQaLMMECWDTKPEKRP 264
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
365-611 3.96e-16

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: 78.62  E-value: 3.96e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLgYWLNKDK--VAIKTIREGAMSEE---DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd08221   4 PVRVLGRGAFGEAVL-YRKTEDNslVVWKEVNLSRLSEKerrDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYCN 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVLDDQY---TSS 515
Cdd:cd08221  83 GGNLHDKIAQQKNqLFPEEVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISK-VLDSESsmaESI 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 TGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIpYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCW 595
Cdd:cd08221 162 VGTPY---YMSPELVQGVKYNFKSDIWAVGCVLYELLTLKRT-FDATNPLRLAVKIVQGEYEDIDEQYSEEIIQLVHDCL 237
                       250
                ....*....|....*.
gi 15718680 596 KERPEDRPAFSRLLRQ 611
Cdd:cd08221 238 HQDPEDRPTAEELLER 253
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
369-574 4.39e-16

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: 78.60  E-value: 4.39e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWL-NKDKVAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14663   8 LGEGTFAKVKFARNTkTGESVAIKIIDKEQVAREGMVEqikrEIAIMKLLRHPNIVELHEVMATKTKIFFVMELVTGGEL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG---MTRFVLDDQYTSST-GTK 519
Cdd:cd14663  88 FSKIAKN-GRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGlsaLSEQFRQDGLLHTTcGTP 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 520 fpvKWASPEVFSFSRY-SSKSDVWSFGVLMWeVFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd14663 167 ---NYVAPEVLARRGYdGAKADIWSCGVILF-VLLAGYLPFDDENLMALYRKIMKG 218
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
235-337 4.63e-16

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: 73.77  E-value: 4.63e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 235 ETYEWYNKSISRDKAEKLLLDTG-KEGAFMVRDSRTA-GTYTVSVftKAVVSENNPCIKHYHIKETNDNpkRYYVAEKYV 312
Cdd:cd09933   1 EAEEWFFGKIKRKDAEKLLLAPGnPRGTFLIRESETTpGAYSLSV--RDGDDARGDTVKHYRIRKLDNG--GYYITTRAT 76
                        90       100
                ....*....|....*....|....*
gi 15718680 313 FDSIPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd09933  77 FPTLQELVQHYSKDADGLCCRLTVP 101
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
366-551 5.00e-16

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: 78.70  E-value: 5.00e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGywlnKDK-----VAIKTIREGAMSE---EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd07860   5 VEKIGEGTYGVVYKA----RNKltgevVALKKIRLDTETEgvpSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MeHGCLSDYLR-TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF--VLDDQYTS 514
Cdd:cd07860  81 L-HQDLKKFMDaSALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAfgVPVRTYTH 159
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 15718680 515 STGTKFpvkWASPEVFSFSR-YSSKSDVWSFGVLMWEV 551
Cdd:cd07860 160 EVVTLW---YRAPEILLGCKyYSTAVDIWSLGCIFAEM 194
BTK smart00107
Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and ...
113-148 5.00e-16

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 128417  Cd Length: 36  Bit Score: 71.64  E-value: 5.00e-16
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 15718680    113 NNSLVPKYHPNFWMDGKWRCCSQLEKLATGCAQYDP 148
Cdd:smart00107   1 NNNLLQKYHPSFWVDGKWLCCQQSEKNAPGCTPYEA 36
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
369-603 5.11e-16

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: 78.07  E-value: 5.11e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWlNKDKVAIKTIREGAmSEEDFIEEAEVMMKLSHPKLVQLYGVCLeqAPICLVFEFMEHGCLSDYLR 448
Cdd:cd14068   2 LGDGGFGSVYRAVY-RGEDVAVKIFNKHT-SFRLLRQELVVLSHLHHPSLVALLAAGT--APRMLVMELAPKGSLDALLQ 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 449 TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV-----GENQVIKVSDFGMTRFVLDDQYTSSTGTKfpvK 523
Cdd:cd14068  78 QDNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYGIAQYCCRMGIKTSEGTP---G 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 524 WASPEVfsfSR----YSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPR-----LASTHVYQIMNHC 594
Cdd:cd14068 155 FRAPEV---ARgnviYNQQADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQGKLPDPVkeygcAPWPGVEALIKDC 231

                ....*....
gi 15718680 595 WKERPEDRP 603
Cdd:cd14068 232 LKENPQCRP 240
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
369-561 6.33e-16

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: 78.52  E-value: 6.33e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDkVAIKTIREgaMSEEDFIEEAEV--MMKLSHPKLVQLYGV--CLE--QAPICLVFEFMEHGC 442
Cdd:cd14053   3 KARGRFGAVWKAQYLNRL-VAVKIFPL--QEKQSWLTEREIysLPGMKHENILQFIGAekHGEslEAEYWLITEFHERGS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQrgLFAAETLLGMCLDVCEGMAYLEE----------ACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd14053  80 LCDYLKGN--VISWNELCKIAESMARGLAYLHEdipatngghkPSIAHRDFKSKNVLLKSDLTACIADFGLALKFEPGKS 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 513 TSST----GTKfpvKWASPEVF----SFSRYSSKS-DVWSFGVLMWEVFS----------EGKIPYEN 561
Cdd:cd14053 158 CGDThgqvGTR---RYMAPEVLegaiNFTRDAFLRiDMYAMGLVLWELLSrcsvhdgpvdEYQLPFEE 222
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
363-609 6.75e-16

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: 78.22  E-value: 6.75e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGY----WLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLY----GVCLEQAPICLV 434
Cdd:cd14031  12 LKFDIELGRGAFKTVYKGLdtetWVEVAWCELQDRKLTKAEQQRFKEEAEMLKGLQHPNIVRFYdsweSVLKGKKCIVLV 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEAC--VIHRDLAARNCLV-GENQVIKVSDFGMTRFVLDDQ 511
Cdd:cd14031  92 TELMTSGTLKTYLKRFK-VMKPKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATLMRTSF 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKfpvKWASPEVFSfSRYSSKSDVWSFGVLMWEVfSEGKIPY-ENRSNSEVVEDISTGFrlyKP----RLASTH 586
Cdd:cd14031 171 AKSVIGTP---EFMAPEMYE-EHYDESVDVYAFGMCMLEM-ATSEYPYsECQNAAQIYRKVTSGI---KPasfnKVTDPE 242
                       250       260
                ....*....|....*....|...
gi 15718680 587 VYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd14031 243 VKEIIEGCIRQNKSERLSIKDLL 265
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
362-609 9.11e-16

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: 78.00  E-value: 9.11e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSE--EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFM 438
Cdd:cd06619   2 DIQYQEILGHGNGGTVYKAYHLLTRRIlAVKVIPLDITVElqKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTqrglfaAETLLG-MCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd06619  82 DGGSLDVYRKI------PEHVLGrIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLVNSIAKTYVG 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPY----ENRSNSEVVEDISTGFRLYKPRLA----STHVYQ 589
Cdd:cd06619 156 TN---AYMAPERISGEQYGIHSDVWSLGISFMELAL-GRFPYpqiqKNQGSLMPLQLLQCIVDEDPPVLPvgqfSEKFVH 231
                       250       260
                ....*....|....*....|
gi 15718680 590 IMNHCWKERPEDRPAFSRLL 609
Cdd:cd06619 232 FITQCMRKQPKERPAPENLM 251
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
369-571 9.66e-16

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK 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: 270976 [Multi-domain]  Cd Length: 258  Bit Score: 77.45  E-value: 9.66e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLG-YWLNKDKVAIKTIREGAM---SEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14074  11 LGRGHFAVVKLArHVFTGEKVAVKVIDKTKLddvSKAHLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILELGDGGDMY 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DY-LRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ-VIKVSDFGMT-RFVLDDQYTSSTGTkfp 521
Cdd:cd14074  91 DYiMKHENGL-NEDLARKYFRQIVSAISYCHKLHVVHRDLKPENVVFFEKQgLVKLTDFGFSnKFQPGEKLETSCGS--- 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 522 VKWASPEVFSFSRYSS-KSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14074 167 LAYSAPEILLGDEYDApAVDIWSLGVILYMLVC-GQPPFQEANDSETLTMI 216
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
366-616 1.08e-15

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: 77.76  E-value: 1.08e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAM-SEEDFIEEAEVMMKLS-HPKLVQLYGVCLEQAP----ICLVFEFM 438
Cdd:cd13985   5 TKQLGEGGFSYVYLAHDVNTGRrYALKRMYFNDEeQLRVAIKEIEIMKRLCgHPNIVQYYDSAILSSEgrkeVLLLMEYC 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EhGCLSDYLR-TQRGLFAAETLLGMCLDVCEGMAYL--EEACVIHRDLAARNCLVGENQVIKVSDFGmtrfvlddqyTSS 515
Cdd:cd13985  85 P-GSLVDILEkSPPSPLSEEEVLRIFYQICQAVGHLhsQSPPIIHRDIKIENILFSNTGRFKLCDFG----------SAT 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 TGTKFPVKWA------------------SPE---VFSFSRYSSKSDVWSFGVLMWE-VFSegKIPYEnrsNSEVVEDIST 573
Cdd:cd13985 154 TEHYPLERAEevniieeeiqknttpmyrAPEmidLYSKKPIGEKADIWALGCLLYKlCFF--KLPFD---ESSKLAIVAG 228
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 15718680 574 GFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd13985 229 KYSIPEQPRYSPELHDLIRHMLTPDPAERPDIFQVINIITKDT 271
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
361-587 1.15e-15

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: 77.86  E-value: 1.15e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGywlnKDKVAIKTIREGAMSEEDFIE---------EAEVMMKLSHPKLVQLYGVCLEQAPI 431
Cdd:cd05612   1 DDFERIKTIGTGTFGRVHLV----RDRISEHYYALKVMAIPEVIRlkqeqhvhnEKRVLKEVSHPFIIRLFWTEHDQRFL 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDYLRTqRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ 511
Cdd:cd05612  77 YMLMEYVPGGELFSYLRN-SGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKLRDRT 155
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 512 YTsSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfRLYKPRLASTHV 587
Cdd:cd05612 156 WT-LCGTP---EYLAPEVIQSKGHNKAVDWWALGILIYEMLV-GYPPFFDDNPFGIYEKILAG-KLEFPRHLDLYA 225
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
404-558 1.27e-15

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: 78.17  E-value: 1.27e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 404 IEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEAC-VIHRD 482
Cdd:cd06650  51 IRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLK-KAGRIPEQILGKVSIAVIKGLTYLREKHkIMHRD 129
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 483 LAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIP 558
Cdd:cd06650 130 VKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTR---SYMSPERLQGTHYSVQSDIWSMGLSLVEM-AVGRYP 201
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
369-603 1.36e-15

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: 77.36  E-value: 1.36e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIR-EGAMSEE---DFIE----EAEVMMKLSHPKLVQLYGVC-LEQAPICLVFEFM 438
Cdd:cd13990   8 LGKGGFSEVYKAFDLVEQRyVACKIHQlNKDWSEEkkqNYIKhalrEYEIHKSLDHPRIVKLYDVFeIDTDSFCTVLEYC 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQRGLFAAETLLgMCLDVCEGMAYLEEAC--VIHRDLAARNCLVGENQV---IKVSDFGMTRFVLDDQYT 513
Cdd:cd13990  88 DGNDLDFYLKQHKSIPEREARS-IIMQVVSALKYLNEIKppIIHYDLKPGNILLHSGNVsgeIKITDFGLSKIMDDESYN 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SST--------GTkfpVKWASPEVF----SFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVV---------EDIS 572
Cdd:cd13990 167 SDGmeltsqgaGT---YWYLPPECFvvgkTPPKISSKVDVWSVGVIFYQMLY-GRKPFGHNQSQEAIleentilkaTEVE 242
                       250       260       270
                ....*....|....*....|....*....|.
gi 15718680 573 TGFrlyKPRLaSTHVYQIMNHCWKERPEDRP 603
Cdd:cd13990 243 FPS---KPVV-SSEAKDFIRRCLTYRKEDRP 269
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
367-571 1.39e-15

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: 76.85  E-value: 1.39e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14114   8 EELGTGAFGVVHRCTERATGNNfAAKFIMTPHESDKETVRkEIQIMNQLHHPKLINLHDAFEDDNEMVLILEFLSGGELF 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN--CLVGENQVIKVSDFGM-TRFVLDDQYTSSTGTkfp 521
Cdd:cd14114  88 ERIAAEHYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENimCTTKRSNEVKLIDFGLaTHLDPKESVKVTTGT--- 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 15718680 522 VKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14114 165 AEFAAPEIVEREPVGFYTDMWAVGVLSYVLLS-GLSPFAGENDDETLRNV 213
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
404-550 1.59e-15

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: 77.86  E-value: 1.59e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 404 IEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLfaAETLLG-MCLDVCEGMAYL-EEACVIHR 481
Cdd:cd06615  47 IRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRI--PENILGkISIAVLRGLTYLrEKHKIMHR 124
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 482 DLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd06615 125 DVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTR---SYMSPERLQGTHYTVQSDIWSLGLSLVE 190
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
361-571 1.64e-15

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: 78.11  E-value: 1.64e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLSHPK-LVQLYGVCLEQAPICLV 434
Cdd:cd05615  10 TDFNFLMVLGKGSFGKVMLAERKGSDELyAIKILKKDVVIQDDDVEctmvEKRVLALQDKPPfLTQLHSCFQTVDRLYFV 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd05615  90 MEYVNGGDLMYHIQ-QVGKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMVEGVTT 168
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 515 STGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05615 169 RTFCGTP-DYIAPEIIAYQPYGRSVDWWAYGVLLYEMLA-GQPPFDGEDEDELFQSI 223
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
390-574 1.87e-15

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: 76.53  E-value: 1.87e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 390 IKTIREGamsEEDFIEEAEVMMKLSHPKLVQLYGVCL--EQAPICLVFEFMeHGCLSDYLRTQRG----LFAAETLLgmc 463
Cdd:cd14119  31 LRRIPNG---EANVKREIQILRRLNHRNVIKLVDVLYneEKQKLYMVMEYC-VGGLQEMLDSAPDkrlpIWQAHGYF--- 103
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 464 LDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG----MTRFVLDDQYTSSTGTkfPvKWASPEVFSFSRYSS-- 537
Cdd:cd14119 104 VQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGvaeaLDLFAEDDTCTTSQGS--P-AFQPPEIANGQDSFSgf 180
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15718680 538 KSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd14119 181 KVDIWSAGVTLYNMTT-GKYPFEGDNIYKLFENIGKG 216
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
235-337 1.87e-15

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: 72.30  E-value: 1.87e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 235 ETYEWYNKSISRDKAEKLLLDTG-KEGAFMVRDSRTA-GTYTVSVftKAVVSENNPCIKHYHIKeTNDNPKrYYVAEKYV 312
Cdd:cd10363   1 ETEEWFFKGISRKDAERQLLAPGnMLGSFMIRDSETTkGSYSLSV--RDYDPQHGDTVKHYKIR-TLDNGG-FYISPRST 76
                        90       100
                ....*....|....*....|....*
gi 15718680 313 FDSIPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd10363  77 FSTLQELVDHYKKGNDGLCQKLSVP 101
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
366-558 1.87e-15

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: 77.78  E-value: 1.87e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVH-LGYWLNKDKVAIKTIR---EGAMSEEdFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd06649  10 ISELGAGNGGVVTkVQHKPSGLIMARKLIHleiKPAIRNQ-IIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGG 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGLfaAETLLG-MCLDVCEGMAYLEEA-CVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTK 519
Cdd:cd06649  89 SLDQVLKEAKRI--PEEILGkVSIAVLRGLAYLREKhQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTR 166
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 15718680 520 fpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGKIP 558
Cdd:cd06649 167 ---SYMSPERLQGTHYSVQSDIWSMGLSLVEL-AIGRYP 201
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
369-615 1.89e-15

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: 76.93  E-value: 1.89e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWlnKDKVAIKTIR-EGAMSEEDFIEEAEVM--MKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 445
Cdd:cd14152   8 IGQGRWGKVHRGRW--HGEVAIRLLEiDGNNQDHLKLFKKEVMnyRQTRHENVVLFMGACMHPPHLAIITSFCKGRTLYS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIkVSD---FGMTRFVLDDQYTSStgTKFPV 522
Cdd:cd14152  86 FVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDfglFGISGVVQEGRRENE--LKLPH 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 523 KWA---SPEVFSFSR---------YSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTGFRLyKPRLAST----H 586
Cdd:cd14152 163 DWLcylAPEIVREMTpgkdedclpFSKAADVYAFGTIWYELQAR-DWPLKNQPAEALIWQIGSGEGM-KQVLTTIslgkE 240
                       250       260
                ....*....|....*....|....*....
gi 15718680 587 VYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14152 241 VTEILSACWAFDLEERPSFTLLMDMLEKL 269
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
369-591 2.07e-15

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: 77.10  E-value: 2.07e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLgyWLNKD---KVAIKTIR-EGAMSE---EDFIEEAEVMMKLSHPKLV-------QLYGVCLEQAPIcLV 434
Cdd:cd13989   1 LGSGGFGYVTL--WKHQDtgeYVAIKKCRqELSPSDknrERWCLEVQIMKKLNHPNVVsardvppELEKLSPNDLPL-LA 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQR---GLFAAE--TLLGmclDVCEGMAYLEEACVIHRDLAARNCLV--GENQVI-KVSDFGMTRf 506
Cdd:cd13989  78 MEYCSGGDLRKVLNQPEnccGLKESEvrTLLS---DISSAISYLHENRIIHRDLKPENIVLqqGGGRVIyKLIDLGYAK- 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 VLDDQY--TSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEV------FSEGKIPYE------NRSNSEVV--ED 570
Cdd:cd13989 154 ELDQGSlcTSFVGT---LQYLAPELFESKKYTCTVDYWSFGTLAFECitgyrpFLPNWQPVQwhgkvkQKKPEHICayED 230
                       250       260
                ....*....|....*....|.
gi 15718680 571 ISTGFRLYKPRLASTHVYQIM 591
Cdd:cd13989 231 LTGEVKFSSELPSPNHLSSIL 251
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
361-581 2.36e-15

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 77.55  E-value: 2.36e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  361 SELTFVQEIGSGQFGLVHLGYWLNKDK-VAIKTIREGA---MSEEDFI-EEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:PTZ00263  18 SDFEMGETLGTGSFGRVRIAKHKGTGEyYAIKCLKKREilkMKQVQHVaQEKSILMELSHPFIVNMMCSFQDENRVYFLL 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  436 EFMEHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTsS 515
Cdd:PTZ00263  98 EFVVGGELFTHLRKA-GRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVPDRTFT-L 175
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680  516 TGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPYENRSNSEVVEDISTGfRLYKPR 581
Cdd:PTZ00263 176 CGTP---EYLAPEVIQSKGHGKAVDWWTMGVLLYE-FIAGYPPFFDDTPFRIYEKILAG-RLKFPN 236
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
367-553 2.59e-15

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: 77.02  E-value: 2.59e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYwLNKDKVAIKTIreGAMSEEDFIEEAEVM--MKLSHPKLVQLYGVCLEQAPIC-----LVFEFME 439
Cdd:cd14054   1 QLIGQGRYGTVWKGS-LDERPVAVKVF--PARHRQNFQNEKDIYelPLMEHSNILRFIGADERPTADGrmeylLVLEYAP 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGLFaaETLLGMCLDVCEGMAYLEE---------ACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD 510
Cdd:cd14054  78 KGSLCSYLRENTLDW--MSSCRMALSLTRGLAYLHTdlrrgdqykPAIAHRDLNSRNVLVKADGSCVICDFGLAMVLRGS 155
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680 511 QYT------------SSTGTkfpVKWASPEVF-------SFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd14054 156 SLVrgrpgaaenasiSEVGT---LRYMAPEVLegavnlrDCESALKQVDVYALGLVLWEIAM 214
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
368-571 2.69e-15

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: 76.18  E-value: 2.69e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGywlNKDK----VAIKTIREGAMSEedFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14010   7 EIGRGKHSVVYKG---RRKGtiefVAIKCVDKSKRPE--VLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYCTGGDL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR-----------FVLDDQY 512
Cdd:cd14010  82 ETLLRQDGNL-PESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARregeilkelfgQFSDEGN 160
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 513 TSSTGTKFPVK----WASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14010 161 VNKVSKKQAKRgtpyYMAPELFQGGVHSFASDLWALGCVLYEMFT-GKPPFVAESFTELVEKI 222
SH3_TXK cd11907
Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a ...
176-228 3.00e-15

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212840 [Multi-domain]  Cd Length: 55  Bit Score: 70.37  E-value: 3.00e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 15718680 176 VIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVE 228
Cdd:cd11907   3 VKALYDFLPREPSNLALKRAEEYLILEQYDPHWWKARDRYGNEGLIPSNYVTE 55
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
411-574 3.02e-15

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: 77.00  E-value: 3.02e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 411 MKL--SHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNC 488
Cdd:cd14179  55 LKLceGHPNIVKLHEVYHDQLHTFLVMELLKGGELLERIKKKQ-HFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENL 133
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 489 LV---GENQVIKVSDFGMTRFVLDDQYTSSTGTkFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNS 565
Cdd:cd14179 134 LFtdeSDNSEIKIIDFGFARLKPPDNQPLKTPC-FTLHYAAPELLNYNGYDESCDLWSLGVILYTMLS-GQVPFQCHDKS 211
                       170
                ....*....|....*.
gi 15718680 566 -------EVVEDISTG 574
Cdd:cd14179 212 ltctsaeEIMKKIKQG 227
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
352-609 3.12e-15

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK 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: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 76.11  E-value: 3.12e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 352 RYGKwvidpseltFVQEIGSGQFGLVHLGYwlnkD-----KVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYG 423
Cdd:cd13983   1 RYLK---------FNEVLGRGSFKTVYRAF----DteegiEVAWNEIKLRKLPKAErqrFKQEIEILKSLKHPNIIKFYD 67
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 424 VCLEQAPICLVF--EFMEHGCLSDYLRTQRGLfaAETLLGM-CLDVCEGMAYL--EEACVIHRDLAARNCLV-GENQVIK 497
Cdd:cd13983  68 SWESKSKKEVIFitELMTSGTLKQYLKRFKRL--KLKVIKSwCRQILEGLNYLhtRDPPIIHRDLKCDNIFInGNTGEVK 145
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 498 VSDFGMTRFVLDDQYTSSTGTkfPvKWASPEVFSfSRYSSKSDVWSFGVLMWEVFSeGKIPY-ENRSNSEVVEDISTGfr 576
Cdd:cd13983 146 IGDLGLATLLRQSFAKSVIGT--P-EFMAPEMYE-EHYDEKVDIYAFGMCLLEMAT-GEYPYsECTNAAQIYKKVTSG-- 218
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 15718680 577 lYKP----RLASTHVYQIMNHCWKeRPEDRPAFSRLL 609
Cdd:cd13983 219 -IKPeslsKVKDPELKDFIEKCLK-PPDERPSARELL 253
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
366-600 3.35e-15

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: 76.45  E-value: 3.35e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVhlgyWLNKDKV-----AIKTIR--EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP-------- 430
Cdd:cd14048  11 IQCLGRGGFGVV----FEAKNKVddcnyAVKRIRlpNNELAREKVLREVRALAKLDHPGIVRYFNAWLERPPegwqekmd 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ---ICLVFEFMEHGCLSDYLRTQRGLFAAE--TLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM-- 503
Cdd:cd14048  87 evyLYIQMQLCRKENLKDWMNRRCTMESRElfVCLNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLvt 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 504 ------------TRFVLDDQYTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFsegkipYENRSNSEVVEDI 571
Cdd:cd14048 167 amdqgepeqtvlTPMPAYAKHTGQVGTRL---YMSPEQIHGNQYSEKVDIFALGLILFELI------YSFSTQMERIRTL 237
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 15718680 572 STGFRLYKPRL-------ASTHVYQIMNHCWKERPE 600
Cdd:cd14048 238 TDVRKLKFPALftnkypeERDMVQQMLSPSPSERPE 273
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
369-560 3.54e-15

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 78.68  E-value: 3.54e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  369 IGSGQFGLVHLGY--WLNKDkVAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLY--GvclEQAPIC-LVFEFME 439
Cdd:NF033483  15 IGRGGMAEVYLAKdtRLDRD-VAVKVLRPDLARDPEFVArfrrEAQSAASLSHPNIVSVYdvG---EDGGIPyIVMEYVD 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  440 hGC-LSDYLRTQRGLFAAETLlGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVlddqyTSST-- 516
Cdd:NF033483  91 -GRtLKDYIREHGPLSPEEAV-EIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARAL-----SSTTmt 163
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 15718680  517 ------GTkfpVKWASPEVfsfSRYSS---KSDVWSFGVLMWEVFSeGKIPYE 560
Cdd:NF033483 164 qtnsvlGT---VHYLSPEQ---ARGGTvdaRSDIYSLGIVLYEMLT-GRPPFD 209
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
369-611 3.81e-15

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: 76.89  E-value: 3.81e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE----EAEVM-MKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd05619  13 LGKGSFGKVFLAELKGTNQfFAIKALKKDVVLMDDDVEctmvEKRVLsLAWEHPFLTHLFCTFQTKENLFFVMEYLNGGD 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRT-------QRGLFAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR-FVLDDQYTS 514
Cdd:cd05619  93 LMFHIQSchkfdlpRATFYAAEIICGL--------QFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKeNMLGDAKTS 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 S-TGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYkPRLASTHVYQIMNH 593
Cdd:cd05619 165 TfCGTP---DYIAPEILLGQKYNTSVDWWSFGVLLYEMLI-GQSPFHGQDEEELFQSIRMDNPFY-PRWLEKEAKDILVK 239
                       250
                ....*....|....*...
gi 15718680 594 CWKERPEDRPAFSRLLRQ 611
Cdd:cd05619 240 LFVREPERRLGVRGDIRQ 257
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
177-223 4.59e-15

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 69.54  E-value: 4.59e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 15718680   177 IALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPS 223
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEGLIPS 47
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
367-571 4.67e-15

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: 76.48  E-value: 4.67e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVM-MKLSHPKLVQLYgvCLEQAP--ICLVFEFM 438
Cdd:cd05590   1 RVLGKGSFGKVMLARLKESGRLyAVKVLKKDVILQDDDVEctmtEKRILsLARNHPFLTQLY--CCFQTPdrLFFVMEFV 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTQR-------GLFAAEtllgmcldVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ 511
Cdd:cd05590  79 NGGDLMFHIQKSRrfdearaRFYAAE--------ITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNG 150
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05590 151 KTTSTFCGTP-DYIAPEILQEMLYGPSVDWWAMGVLLYEMLC-GHAPFEAENEDDLFEAI 208
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
369-553 4.77e-15

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: 75.92  E-value: 4.77e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHlgYWLNKDK---VAIKTIREgamSEED------FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd07846   9 VGEGSYGMVM--KCRHKETgqiVAIKKFLE---SEDDkmvkkiAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFVD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL--DDQYTSSTG 517
Cdd:cd07846  84 HTVLDDLEKYPNGL-DESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLAapGEVYTDYVA 162
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15718680 518 TKFpvkWASPE-VFSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd07846 163 TRW---YRAPElLVGDTKYGKAVDVWAVGCLVTEMLT 196
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
367-572 5.58e-15

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: 75.44  E-value: 5.58e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLV-----------HLGYWLNKDKVaiKTIREGaMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd14194  11 EELGSGQFAVVkkcrekstglqYAAKFIKKRRT--KSSRRG-VSREDIEREVSILKEIQHPNVITLHEVYENKTDVILIL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRGLFAAET--LLGMCLDvceGMAYLEEACVIHRDLAARNCLVGENQV----IKVSDFGMT-RFVL 508
Cdd:cd14194  88 ELVAGGELFDFLAEKESLTEEEAteFLKQILN---GVYYLHSLQIAHFDLKPENIMLLDRNVpkprIKIIDFGLAhKIDF 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 509 DDQYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDIS 572
Cdd:cd14194 165 GNEFKNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETLANVS 224
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
361-609 6.16e-15

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: 75.86  E-value: 6.16e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIRE--GAMSEEDFIEEAEVMMKLSH-PKLVQLYGVCLEQ--APICLv 434
Cdd:cd06616   6 EDLKDLGEIGRGAFGTVNKMLHKPSGTImAVKRIRStvDEKEQKRLLMDLDVVMRSSDcPYIVKFYGALFREgdCWICM- 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 fEFMEHGCLSDYLRT---QRGLFAAETLLGMCLDVCEGMAYL-EEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD 510
Cdd:cd06616  85 -ELMDISLDKFYKYVyevLDSVIPEEILGKIAVATVKALNYLkEELKIIHRDVKPSNILLDRNGNIKLCDFGISGQLVDS 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 511 -QYTSSTGTKfpvKWASPEVFSFSR----YSSKSDVWSFGVLMWEVfSEGKIPYenRSNSEVVEDISTGFRLYKPRLAST 585
Cdd:cd06616 164 iAKTRDAGCR---PYMAPERIDPSAsrdgYDVRSDVWSLGITLYEV-ATGKFPY--PKWNSVFDQLTQVVKGDPPILSNS 237
                       250       260       270
                ....*....|....*....|....*....|.
gi 15718680 586 HVY-------QIMNHCWKERPEDRPAFSRLL 609
Cdd:cd06616 238 EERefspsfvNFVNLCLIKDESKRPKYKELL 268
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
369-615 6.56e-15

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: 75.43  E-value: 6.56e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWlnKDKVAIKTI---REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 445
Cdd:cd14153   8 IGKGRFGQVYHGRW--HGEVAIRLIdieRDNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIkVSDFGMtrFVLDDQYTSSTGT---KFPV 522
Cdd:cd14153  86 VVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGL--FTISGVLQAGRREdklRIQS 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 523 KW---ASPEVFSFSR---------YSSKSDVWSFGVLMWEVFSEgKIPYENRSNSEVVEDISTGFrlyKPRLAS----TH 586
Cdd:cd14153 163 GWlchLAPEIIRQLSpeteedklpFSKHSDVFAFGTIWYELHAR-EWPFKTQPAEAIIWQVGSGM---KPNLSQigmgKE 238
                       250       260
                ....*....|....*....|....*....
gi 15718680 587 VYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14153 239 ISDILLFCWAYEQEERPTFSKLMEMLEKL 267
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
360-585 7.85e-15

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: 76.21  E-value: 7.85e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 360 PSELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAM----SEEDFIEEAEVMMK-LSHPKLVQLYGVCLEQAPICL 433
Cdd:cd05602   6 PSDFHFLKVIGKGSFGKVLLARHKSDEKFyAVKVLQKKAIlkkkEEKHIMSERNVLLKnVKHPFLVGLHFSFQTTDKLYF 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRTQRGLFAAETLLgMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd05602  86 VLDYINGGELFYHLQRERCFLEPRARF-YAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIEPNGT 164
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680 514 SSTGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYKPRLAST 585
Cdd:cd05602 165 TSTFCGTP-EYLAPEVLHKQPYDRTVDWWCLGAVLYEMLY-GLPPFYSRNTAEMYDNILNKPLQLKPNITNS 234
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
367-574 7.93e-15

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: 74.83  E-value: 7.93e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQF-----------GLVHLGYWLNKDKVaiKTIREGaMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd14105  11 EELGSGQFavvkkcrekstGLEYAAKFIKKRRS--KASRRG-VSREDIEREVSILRQVLHPNIITLHDVFENKTDVVLIL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRGLFAAET--LLGMCLDvceGMAYLEEACVIHRDLAARNCLVGENQV----IKVSDFGMTRFVLD 509
Cdd:cd14105  88 ELVAGGELFDFLAEKESLSEEEAteFLKQILD---GVNYLHTKNIAHFDLKPENIMLLDKNVpiprIKLIDFGLAHKIED 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 510 DQ-YTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd14105 165 GNeFKNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETLANITAV 226
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
365-609 9.21e-15

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: 74.34  E-value: 9.21e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVhlgyWLNKDKV-----AIKTIRE---GAMSEEDFIEEAEVMMKLS-HPKLVQLYGVCLEQAPICLVF 435
Cdd:cd13997   4 ELEQIGSGSFSEV----FKVRSKVdgclyAVKKSKKpfrGPKERARALREVEAHAALGqHPNIVRYYSSWEEGGHLYIQM 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLR--TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMtrfvlddqyT 513
Cdd:cd13997  80 ELCENGSLQDALEelSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGL---------A 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTGTKFPV-----KWASPEVFS-FSRYSSKSDVWSFGVLMWEVFSEGKIPyenrSNSEVVEDISTGFRLYKPRLA-STH 586
Cdd:cd13997 151 TRLETSGDVeegdsRYLAPELLNeNYTHLPKADIFSLGVTVYEAATGEPLP----RNGQQWQQLRQGKLPLPPGLVlSQE 226
                       250       260
                ....*....|....*....|...
gi 15718680 587 VYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd13997 227 LTRLLKVMLDPDPTRRPTADQLL 249
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
172-226 1.05e-14

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 68.72  E-value: 1.05e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 15718680    172 EETVVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYL 226
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYV 55
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
367-561 1.07e-14

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: 74.26  E-value: 1.07e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGY-WLNKDKVAIKTIREGAmSEEDFIE-----EAEVMMKLSHPKLVQLYGVcLEQA--PICLVFEFM 438
Cdd:cd14163   6 KTIGEGTYSKVKEAFsKKHQRKVAIKIIDKSG-GPEEFIQrflprELQIVERLDHKNIIHVYEM-LESAdgKIYLVMELA 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVgENQVIKVSDFGMTRFVLDDQYTSSTGT 518
Cdd:cd14163  84 EDGDVFDCV-LHGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALL-QGFTLKLTDFGFAKQLPKGGRELSQTF 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 15718680 519 KFPVKWASPEVFS-FSRYSSKSDVWSFGVLMWeVFSEGKIPYEN 561
Cdd:cd14163 162 CGSTAYAAPEVLQgVPHDSRKGDIWSMGVVLY-VMLCAQLPFDD 204
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
384-571 1.15e-14

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: 74.13  E-value: 1.15e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 384 NKDKVAIKTIREGAM----SEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETL 459
Cdd:cd14099  25 TGKVYAGKVVPKSSLtkpkQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLELCSNGSLMELLKRRKALTEPEVR 104
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 460 LGMcLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST--GTkfPvKWASPEVFSFSR-YS 536
Cdd:cd14099 105 YFM-RQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLEYDGERKKTlcGT--P-NYIAPEVLEKKKgHS 180
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15718680 537 SKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14099 181 FEVDIWSLGVILYTLLV-GKPPFETSDVKETYKRI 214
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
359-551 1.23e-14

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: 74.31  E-value: 1.23e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSE-LTFVQEIGSGQFGLVHLGYWLNKDKVA-IKTIREGAMSEEDFIEEAEVMMK-LSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd06645   8 NPQEdFELIQRIGSGTYGDVYKARNVNTGELAaIKVIKLEPGEDFAVVQQEIIMMKdCKHSNIVAYFGSYLRRDKLWICM 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD--QYT 513
Cdd:cd06645  88 EFCGGGSLQDIYHVT-GPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATiaKRK 166
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 15718680 514 SSTGTKFpvkWASPEVFSFSR---YSSKSDVWSFGVLMWEV 551
Cdd:cd06645 167 SFIGTPY---WMAPEVAAVERkggYNQLCDIWAVGITAIEL 204
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
369-550 1.50e-14

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: 74.61  E-value: 1.50e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLgyWLNKD---KVAIKTIRE--GAMSEEDFIEEAEVMMKLSHPKLV-------QLYGVCLEQAPIcLVFE 436
Cdd:cd14038   2 LGTGGFGNVLR--WINQEtgeQVAIKQCRQelSPKNRERWCLEIQIMKRLNHPNVVaardvpeGLQKLAPNDLPL-LAME 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGCLSDYLRTQR---GLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV--GENQVI-KVSDFGMTRFVldD 510
Cdd:cd14038  79 YCQGGDLRKYLNQFEnccGL-REGAILTLLSDISSALRYLHENRIIHRDLKPENIVLqqGEQRLIhKIIDLGYAKEL--D 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 15718680 511 Q---YTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd14038 156 QgslCTSFVGT---LQYLAPELLEQQKYTVTVDYWSFGTLAFE 195
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
364-552 1.51e-14

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: 75.25  E-value: 1.51e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGY-WLNKDKVAIKTIRegaMSEEDFIE------EAEVMMKLSHPKLVQLYGVCLEQAP-----I 431
Cdd:cd07834   3 ELLKPIGSGAYGVVCSAYdKRTGRKVAIKKIS---NVFDDLIDakrilrEIKILRHLKHENIIGLLDILRPPSPeefndV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGcLSDYLRTQRGL-------FAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMT 504
Cdd:cd07834  80 YIVTELMETD-LHKVIKSPQPLtddhiqyFLYQILRGL--------KYLHSAGVIHRDLKPSNILVNSNCDLKICDFGLA 150
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 505 RFVlDDQYTSSTGTKFPV-KW-ASPEV-FSFSRYSSKSDVWSFGVLMWEVF 552
Cdd:cd07834 151 RGV-DPDEDKGFLTEYVVtRWyRAPELlLSSKKYTKAIDIWSVGCIFAELL 200
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
369-554 1.57e-14

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: 74.33  E-value: 1.57e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHlgYWLNKDK---VAIKTIREgamSEEDF----IEEAEVMM--KLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd07847   9 IGEGSYGVVF--KCRNRETgqiVAIKKFVE---SEDDPvikkIALREIRMlkQLKHPNLVNLIEVFRRKRKLHLVFEYCD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL--DDQYTSSTG 517
Cdd:cd07847  84 HTVLNELEKNPRGV-PEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILTgpGDDYTDYVA 162
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 15718680 518 TKFpvkWASPEVF-SFSRYSSKSDVWSFGVlmweVFSE 554
Cdd:cd07847 163 TRW---YRAPELLvGDTQYGPPVDVWAIGC----VFAE 193
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
369-618 1.57e-14

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK 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: 270938 [Multi-domain]  Cd Length: 282  Bit Score: 74.47  E-value: 1.57e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSE-EDFIEEAEVMMKLS-HPKLVQLYGVCL--------EQAPICLVFEF 437
Cdd:cd14036   8 IAEGGFAFVYEAQDVGTGKeYALKRLLSNEEEKnKAIIQEINFMKKLSgHPNIVQFCSAASigkeesdqGQAEYLLLTEL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEhGCLSDYLRT--QRGLFAAETLLGMCLDVCEGMAYL--EEACVIHRDLAARNCLVGENQVIKVSDFG----------- 502
Cdd:cd14036  88 CK-GQLVDFVKKveAPGPFSPDTVLKIFYQTCRAVQHMhkQSPPIIHRDLKIENLLIGNQGQIKLCDFGsatteahypdy 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 503 ----MTRFVLDDQYTSSTGtkfPVkWASPEVFS-FSRY--SSKSDVWSFG-VLMWEVFSegKIPYENRSNSEVvedISTG 574
Cdd:cd14036 167 swsaQKRSLVEDEITRNTT---PM-YRTPEMIDlYSNYpiGEKQDIWALGcILYLLCFR--KHPFEDGAKLRI---INAK 237
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 15718680 575 FRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd14036 238 YTIPPNDTQYTVFHDLIRSTLKVNPEERLSITEIVEQLQELAAA 281
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
235-337 1.66e-14

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: 69.63  E-value: 1.66e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 235 ETYEWYNKSISRDKAEKLLLDTG-KEGAFMVRDSRTA-GTYTVSVftKAVVSENNPCIKHYHIKeTNDNPKrYYVAEKYV 312
Cdd:cd10364   1 ETEEWFFKDITRKDAERQLLAPGnSAGAFLIRESETLkGSYSLSV--RDYDPQHGDVIKHYKIR-SLDNGG-YYISPRIT 76
                        90       100
                ....*....|....*....|....*
gi 15718680 313 FDSIPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd10364  77 FPCISDMIKHYQKQSDGLCRRLEKA 101
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
361-571 1.80e-14

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: 75.12  E-value: 1.80e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEED----FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd05593  15 NDFDYLKLLGKGTFGKVILVREKASGKYyAMKILKKEVIIAKDevahTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVM 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd05593  95 EYVNGGELFFHLSRER-VFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGITDAATMK 173
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 516 TGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05593 174 TFCGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHEKLFELI 227
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
364-577 2.19e-14

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: 73.89  E-value: 2.19e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQ--EIGSGQFGLVHLGYW-LNKDKVAIKTIR----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFE 436
Cdd:cd07871   6 TYVKldKLGEGTYATVFKGRSkLTENLVALKEIRleheEGAPCTA--IREVSLLKNLKHANIVTLHDIIHTERCLTLVFE 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF--VLDDQYTS 514
Cdd:cd07871  84 YLDSD-LKQYLDNCGNLMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLARAksVPTKTYSN 162
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 515 STGTKFpvkWASPEVFSFS-RYSSKSDVWSFGVLMWEVfSEGKIPYenrSNSEVVEDISTGFRL 577
Cdd:cd07871 163 EVVTLW---YRPPDVLLGStEYSTPIDMWGVGCILYEM-ATGRPMF---PGSTVKEELHLIFRL 219
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
365-602 2.28e-14

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: 74.64  E-value: 2.28e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLG-YWLNKDKVAIKTIREGAMSEEDFIEEA-------EVMMKLSHPKLVQLYGvCLeQAP--ICLV 434
Cdd:cd05589   3 CIAVLGRGHFGKVLLAeYKPTGELFAIKALKKGDIIARDEVESLmcekrifETVNSARHPFLVNLFA-CF-QTPehVCFV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCL-----SDYLRTQRGLF-AAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVL 508
Cdd:cd05589  81 MEYAAGGDLmmhihEDVFSEPRAVFyAACVVLGL--------QFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKEGM 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 509 DDQYTSST--GTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYkPRLASTH 586
Cdd:cd05589 153 GFGDRTSTfcGTP---EFLAPEVLTDTSYTRAVDWWGLGVLIYEMLV-GESPFPGDDEEEVFDSIVNDEVRY-PRFLSTE 227
                       250
                ....*....|....*.
gi 15718680 587 VYQIMNHCWKERPEDR 602
Cdd:cd05589 228 AISIMRRLLRKNPERR 243
SH3_Nck_1 cd11765
First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
175-226 2.31e-14

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212699 [Multi-domain]  Cd Length: 51  Bit Score: 67.44  E-value: 2.31e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 15718680 175 VVIALYDYQTNDPQELALRRNEEYCLLDSSEiHWWRVQDRNGHEGYVPSSYL 226
Cdd:cd11765   1 YVVAKYDYTAQGDQELSIKKNEKLTLLDDSK-HWWKVQNSSNQTGYVPSNYV 51
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
368-559 2.35e-14

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: 73.85  E-value: 2.35e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGY-----------WLNKDKV-------------AIKTIREGAMSEEDFIE----EAEVMMKLSHPKLV 419
Cdd:cd14199   9 EIGKGSYGVVKLAYneddntyyamkVLSKKKLmrqagfprrppprGARAAPEGCTQPRGPIErvyqEIAILKKLDHPNVV 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 420 QLYGVCLEQAP--ICLVFEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIK 497
Cdd:cd14199  89 KLVEVLDDPSEdhLYMVFELVKQGPVMEVPTLKP--LSEDQARFYFQDLIKGIEYLHYQKIIHRDVKPSNLLVGEDGHIK 166
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 498 VSDFGMT-RFVLDDQYTSST-GTKfpvKWASPEVFSFSR--YSSKS-DVWSFGVLMWeVFSEGKIPY 559
Cdd:cd14199 167 IADFGVSnEFEGSDALLTNTvGTP---AFMAPETLSETRkiFSGKAlDVWAMGVTLY-CFVFGQCPF 229
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
367-571 2.38e-14

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: 73.77  E-value: 2.38e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAM-SEEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14169   9 EKLGEGAFSEVVLAQERGSQRlVALKCIPKKALrGKEAMVEnEIAVLRRINHENIVSLEDIYESPTHLYLAMELVTGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVG---ENQVIKVSDFGMTRFVLDDQYTSSTGTKf 520
Cdd:cd14169  89 FDRI-IERGSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLYAtpfEDSKIMISDFGLSKIEAQGMLSTACGTP- 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 521 pvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14169 167 --GYVAPELLEQKPYGKAVDVWAIGVISYILLC-GYPPFYDENDSELFNQI 214
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
363-609 2.39e-14

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: 73.50  E-value: 2.39e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGywLNKD---KVA---IKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLY----GVCLEQAPIC 432
Cdd:cd14033   3 LKFNIEIGRGSFKTVYRG--LDTEttvEVAwceLQTRKLSKGERQRFSEEVEMLKGLQHPNIVRFYdswkSTVRGHKCII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYLRTQRGLfAAETLLGMCLDVCEGMAYLEEAC--VIHRDLAARNCLV-GENQVIKVSDFGMTRFVLD 509
Cdd:cd14033  81 LVTELMTSGTLKTYLKRFREM-KLKLLQRWSRQILKGLHFLHSRCppILHRDLKCDNIFItGPTGSVKIGDLGLATLKRA 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGTKfpvKWASPEVFSfSRYSSKSDVWSFGVLMWEVfSEGKIPY-ENRSNSEVVEDISTGFR---LYKPRLAst 585
Cdd:cd14033 160 SFAKSVIGTP---EFMAPEMYE-EKYDEAVDVYAFGMCILEM-ATSEYPYsECQNAAQIYRKVTSGIKpdsFYKVKVP-- 232
                       250       260
                ....*....|....*....|....
gi 15718680 586 HVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd14033 233 ELKEIIEGCIRTDKDERFTIQDLL 256
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
367-574 2.67e-14

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: 73.11  E-value: 2.67e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDKV-AIKTIRE-GAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14191   8 ERLGSGKFGQVFRLVEKKTKKVwAGKFFKAySAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVSGGELF 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN--CLVGENQVIKVSDFGMTRFVlddQYTSSTGTKFPV 522
Cdd:cd14191  88 ERIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENimCVNKTGTKIKLIDFGLARRL---ENAGSLKVLFGT 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 15718680 523 -KWASPEVFSFSRYSSKSDVWSFGVLMWeVFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd14191 165 pEFVAPEVINYEPIGYATDMWSIGVICY-ILVSGLSPFMGDNDNETLANVTSA 216
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
369-616 2.70e-14

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes 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, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The TGFbR1 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: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 73.63  E-value: 2.70e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDkVAIKTI--REgamsEEDFIEEAE----VMmkLSHPKLV--------------QLYgvcleq 428
Cdd:cd14143   3 IGKGRFGEVWRGRWRGED-VAVKIFssRE----ERSWFREAEiyqtVM--LRHENILgfiaadnkdngtwtQLW------ 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 429 apicLVFEFMEHGCLSDYLrtQRGLFAAETLLGMCLDVCEGMAYLE--------EACVIHRDLAARNCLVGENQVIKVSD 500
Cdd:cd14143  70 ----LVSDYHEHGSLFDYL--NRYTVTVEGMIKLALSIASGLAHLHmeivgtqgKPAIAHRDLKSKNILVKKNGTCCIAD 143
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 501 FGM------TRFVLDDQYTSSTGTKfpvKWASPEVF-------SFSRYsSKSDVWSFGVLMWEV---------FSEGKIP 558
Cdd:cd14143 144 LGLavrhdsATDTIDIAPNHRVGTK---RYMAPEVLddtinmkHFESF-KRADIYALGLVFWEIarrcsiggiHEDYQLP 219
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 559 YENRSNSE-VVEDIST-----GFRLYKPRLASTH-----VYQIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd14143 220 YYDLVPSDpSIEEMRKvvceqKLRPNIPNRWQSCealrvMAKIMRECWYANGAARLTALRIKKTLSQLS 288
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
238-323 2.84e-14

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: 68.25  E-value: 2.84e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 238 EWYNKSISRDKAEKLLLDtGKEGAFMVRDSRT-AGTYTVSVFTKavvsenNPCIKHYHIKETNDNpKRYYVAEKYVFDSI 316
Cdd:cd00173   1 PWFHGSISREEAERLLRG-KPDGTFLVRESSSePGDYVLSVRSG------DGKVKHYLIERNEGG-YYLLGGSGRTFPSL 72

                ....*..
gi 15718680 317 PLLINYH 323
Cdd:cd00173  73 PELVEHY 79
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
369-602 2.99e-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: 74.17  E-value: 2.99e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVM-MKLSHPKLVQLYGvCLE-QAPICLVFEFMEHG 441
Cdd:cd05570   3 LGKGSFGKVMLAERKKTDELyAIKVLKKEVIIEDDDVEctmtEKRVLaLANRHPFLTGLHA-CFQtEDRLYFVMEYVNGG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRGL-------FAAEtllgmcldVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd05570  82 DLMFHIQRARRFteerarfYAAE--------ICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKEGIWGGNTT 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 ST--GTkfPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYkPRLASTHVYQIMN 592
Cdd:cd05570 154 STfcGT--P-DYIAPEILREQDYGFSVDWWALGVLLYEMLA-GQSPFEGDDEDELFEAILNDEVLY-PRWLSREAVSILK 228
                       250
                ....*....|
gi 15718680 593 HCWKERPEDR 602
Cdd:cd05570 229 GLLTKDPARR 238
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
362-616 3.23e-14

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, 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, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The ACVR1 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: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 73.63  E-value: 3.23e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWlNKDKVAIKTIreGAMSEEDFIEEAE----VMMKlsHPKLVQLYGVCLEQAPIC----L 433
Cdd:cd14142   6 QITLVECIGKGRYGEVWRGQW-QGESVAVKIF--SSRDEKSWFRETEiyntVLLR--HENILGFIASDMTSRNSCtqlwL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLrtQRGLFAAETLLGMCLDVCEGMAYLE--------EACVIHRDLAARNCLVGENQVIKVSDFGMTr 505
Cdd:cd14142  81 ITHYHENGSLYDYL--QRTTLDHQEMLRLALSAASGLVHLHteifgtqgKPAIAHRDLKSKNILVKSNGQCCIADLGLA- 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 fVLDDQYTSS--------TGTKfpvKWASPEVF-------SFSRYSsKSDVWSFGVLMWEV----FSEG-----KIPYEN 561
Cdd:cd14142 158 -VTHSQETNQldvgnnprVGTK---RYMAPEVLdetintdCFESYK-RVDIYAFGLVLWEVarrcVSGGiveeyKPPFYD 232
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 562 RSNSE---------VVEDistGFRLYKP-RLAS----THVYQIMNHCWKERPEDRPAFSRLLRQLAEIA 616
Cdd:cd14142 233 VVPSDpsfedmrkvVCVD---QQRPNIPnRWSSdptlTAMAKLMKECWYQNPSARLTALRIKKTLLKIL 298
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
369-564 3.87e-14

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: 72.89  E-value: 3.87e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLN-KDKVAIKTIrEGAMSEEDFIE-----EAEVMMKLSHPKLVQLYGVcLEQAP--ICLVFEFMEH 440
Cdd:cd14165   9 LGEGSYAKVKSAYSERlKCNVAIKII-DKKKAPDDFVEkflprELEILARLNHKSIIKTYEI-FETSDgkVYIVMELGVQ 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTqRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ----YTSST 516
Cdd:cd14165  87 GDLLEFIKL-RGALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLRDEngriVLSKT 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 517 GTKFPVkWASPEVFSFSRYSSK-SDVWSFGVLMWeVFSEGKIPYENrSN 564
Cdd:cd14165 166 FCGSAA-YAAPEVLQGIPYDPRiYDIWSLGVILY-IMVCGSMPYDD-SN 211
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
366-550 4.20e-14

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: 73.56  E-value: 4.20e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLG-YWLNKDKVAIKTIREGAmSEEDF----IEEAEVMMKLSHPKLVQLYGVCLEQA--------PIC 432
Cdd:cd07865  17 LAKIGQGTFGEVFKArHRKTGQIVALKKVLMEN-EKEGFpitaLREIKILQLLKHENVVNLIEICRTKAtpynrykgSIY 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEH---GCLSdYLRTQRGLFAAETLLGMCLdvcEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR-FVL 508
Cdd:cd07865  96 LVFEFCEHdlaGLLS-NKNVKFTLSEIKKVMKMLL---NGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLARaFSL 171
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 15718680 509 --DDQYTSSTGTKFPVKWASPEVFSFSR-YSSKSDVWSFGVLMWE 550
Cdd:cd07865 172 akNSQPNRYTNRVVTLWYRPPELLLGERdYGPPIDMWGAGCIMAE 216
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
368-569 4.39e-14

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: 73.06  E-value: 4.39e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSE---------------------------EDFIEEAEVMMKLSHPKLV 419
Cdd:cd14200   7 EIGKGSYGVVKLAYNESDDKyYAMKVLSKKKLLKqygfprrppprgskaaqgeqakplaplERVYQEIAILKKLDHVNIV 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 420 QLYGVCLEQAP--ICLVFEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIK 497
Cdd:cd14200  87 KLIEVLDDPAEdnLYMVFDLLRKGPVMEVPSDKP--FSEDQARLYFRDIVLGIEYLHYQKIVHRDIKPSNLLLGDDGHVK 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 498 VSDFGMT-RFVLDDQYTSST-GTKfpvKWASPEVFSFSR--YSSKS-DVWSFGVLMWeVFSEGKIPY--------ENRSN 564
Cdd:cd14200 165 IADFGVSnQFEGNDALLSSTaGTP---AFMAPETLSDSGqsFSGKAlDVWAMGVTLY-CFVYGKCPFidefilalHNKIK 240

                ....*
gi 15718680 565 SEVVE 569
Cdd:cd14200 241 NKPVE 245
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
389-566 4.56e-14

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: 73.20  E-value: 4.56e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 389 AIKTIR------EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVC-LEQAPICLVFEFME---HGCLSDYLRTQRGLFAAET 458
Cdd:cd14001  32 AVKKINskcdkgQRSLYQERLKEEAKILKSLNHPNIVGFRAFTkSEDGSLCLAMEYGGkslNDLIEERYEAGLGPFPAAT 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 459 LLGMCLDVCEGMAYLE-EACVIHRDLAARNCLV-GENQVIKVSDFGMT------RFVLDDQYTSSTGTKfpvKWASPEV- 529
Cdd:cd14001 112 ILKVALSIARALEYLHnEKKILHGDIKSGNVLIkGDFESVKLCDFGVSlpltenLEVDSDPKAQYVGTE---PWKAKEAl 188
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15718680 530 FSFSRYSSKSDVWSFGVLMWEVFSEgKIPYENRSNSE 566
Cdd:cd14001 189 EEGGVITDKADIFAYGLVLWEMMTL-SVPHLNLLDIE 224
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
363-609 5.25e-14

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-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: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 72.42  E-value: 5.25e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGY----WLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP----ICLV 434
Cdd:cd14032   3 LKFDIELGRGSFKTVYKGLdtetWVEVAWCELQDRKLTKVERQRFKEEAEMLKGLQHPNIVRFYDFWESCAKgkrcIVLV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEAC--VIHRDLAARNCLV-GENQVIKVSDFGMTRFVLDDQ 511
Cdd:cd14032  83 TELMTSGTLKTYLKRFK-VMKPKVLRSWCRQILKGLLFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATLKRASF 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKfpvKWASPEVFSfSRYSSKSDVWSFGVLMWEVfSEGKIPY-ENRSNSEVVEDISTGFRLYK-PRLASTHVYQ 589
Cdd:cd14032 162 AKSVIGTP---EFMAPEMYE-EHYDESVDVYAFGMCMLEM-ATSEYPYsECQNAAQIYRKVTCGIKPASfEKVTDPEIKE 236
                       250       260
                ....*....|....*....|
gi 15718680 590 IMNHCWKERPEDRPAFSRLL 609
Cdd:cd14032 237 IIGECICKNKEERYEIKDLL 256
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
369-547 5.60e-14

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: 71.92  E-value: 5.60e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYW-LNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYL 447
Cdd:cd14006   1 LGRGRFGVVKRCIEkATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGELLDRL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 448 RTQRGLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARNCLV---GENQvIKVSDFGMTRFVLDDQYTSS-TGTkfpVK 523
Cdd:cd14006  81 AERGSLSEEEVRTYM-RQLLEGLQYLHNHHILHLDLKPENILLadrPSPQ-IKIIDFGLARKLNPGEELKEiFGT---PE 155
                       170       180
                ....*....|....*....|....
gi 15718680 524 WASPEVFSFSRYSSKSDVWSFGVL 547
Cdd:cd14006 156 FVAPEIVNGEPVSLATDMWSIGVL 179
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
369-602 6.34e-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: 73.05  E-value: 6.34e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDFIE----EAEVM-MKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd05620   3 LGKGSFGKVLLAELKGKGEyFAVKALKKDVVLIDDDVEctmvEKRVLaLAWENPFLTHLYCTFQTKEHLFFVMEFLNGGD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQ------RGLFAAETLlgMCldvceGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR--FVLDDQYTS 514
Cdd:cd05620  83 LMFHIQDKgrfdlyRATFYAAEI--VC-----GLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKenVFGDNRAST 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 515 STGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYkPRLASTHVYQIMNHC 594
Cdd:cd05620 156 FCGTP---DYIAPEILQGLKYTFSVDWWSFGVLLYEMLI-GQSPFHGDDEDELFESIRVDTPHY-PRWITKESKDILEKL 230

                ....*...
gi 15718680 595 WKERPEDR 602
Cdd:cd05620 231 FERDPTRR 238
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
363-545 6.56e-14

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: 72.54  E-value: 6.56e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYWLN-KDKVAIKTI--------REgamseedfieeAEVMMKLSHPKLVQLYGVCLEQAP--- 430
Cdd:cd14137   6 YTIEKVIGSGSFGVVYQAKLLEtGEVVAIKKVlqdkryknRE-----------LQIMRRLKHPNIVKLKYFFYSSGEkkd 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ---ICLVFEFME---HGCLSDYLRTQRG-------LFAAEtllgmcldVCEGMAYLEEACVIHRDLAARNCLV-GENQVI 496
Cdd:cd14137  75 evyLNLVMEYMPetlYRVIRHYSKNKQTipiiyvkLYSYQ--------LFRGLAYLHSLGICHRDIKPQNLLVdPETGVL 146
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 15718680 497 KVSDFGMTRFVLDDQ----YTSStgtKFpvkWASPE-VFSFSRYSSKSDVWSFG 545
Cdd:cd14137 147 KLCDFGSAKRLVPGEpnvsYICS---RY---YRAPElIFGATDYTTAIDIWSAG 194
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
369-580 6.62e-14

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: 72.18  E-value: 6.62e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFG-LVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYL 447
Cdd:cd14087   9 IGRGSFSrVVRVEHRVTRQPYAIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGGELFDRI 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 448 RTqRGLFA---AETLLGMCLDvceGMAYLEEACVIHRDLAARNCLV---GENQVIKVSDFGM--TRFVLDDQYTSST-GT 518
Cdd:cd14087  89 IA-KGSFTerdATRVLQMVLD---GVKYLHGLGITHRDLKPENLLYyhpGPDSKIMITDFGLasTRKKGPNCLMKTTcGT 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680 519 KfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYKP 580
Cdd:cd14087 165 P---EYIAPEILLRKPYTQSVDMWAVGVIAYILLS-GTMPFDDDNRTRLYRQILRAKYSYSG 222
PH pfam00169
PH domain; PH stands for pleckstrin homology.
5-111 7.51e-14

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 67.97  E-value: 7.51e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680     5 ILLEEQLIKKSQQKRrtspSNFKVRFFVLTKASLAYFEDRHGKK-RTLKGSIELSRIKCVEIVKSDisiPCHYKYPFQVV 83
Cdd:pfam00169   1 VVKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKDDKSGKsKEPKGSISLSGCEVVEVVASD---SPKRKFCFELR 73
                          90       100       110
                  ....*....|....*....|....*....|..
gi 15718680    84 HDNY----LLYVFAPDRESRQRWVLALKEETR 111
Cdd:pfam00169  74 TGERtgkrTYLLQAESEEERKDWIKAIQSAIR 105
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
366-551 9.04e-14

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: 72.89  E-value: 9.04e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQE-IGSGQFGLV------HLGywlnkDKVAIKTIR---EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP----- 430
Cdd:cd07859   4 IQEvIGKGSYGVVcsaidtHTG-----EKVAIKKINdvfEHVSDATRILREIKLLRLLRHPDIVEIKHIMLPPSRrefkd 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFME---HGCL--SDYLRTQRGLFAAETLLgmcldvcEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR 505
Cdd:cd07859  79 IYVVFELMEsdlHQVIkaNDDLTPEHHQFFLYQLL-------RALKYIHTANVFHRDLKPKNILANADCKLKICDFGLAR 151
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 FVLDDQYTSSTGTKF-PVKW-ASPEVFS--FSRYSSKSDVWSFGVLMWEV 551
Cdd:cd07859 152 VAFNDTPTAIFWTDYvATRWyRAPELCGsfFSKYTPAIDIWSIGCIFAEV 201
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
367-574 9.18e-14

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: 72.37  E-value: 9.18e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGL----VHLGywlNKDKVAIKTIREgamSEEDFIEEAEVMMKL-SHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd14175   7 ETIGVGSYSVckrcVHKA---TNMEYAVKVIDK---SKRDPSEEIEILLRYgQHPNIITLKDVYDDGKHVYLVTELMRGG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV----GENQVIKVSDFGMTRFVLDDQYTSSTG 517
Cdd:cd14175  81 ELLDKILRQK-FFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYvdesGNPESLRICDFGFAKQLRAENGLLMTP 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 TkFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYEN---RSNSEVVEDISTG 574
Cdd:cd14175 160 C-YTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLA-GYTPFANgpsDTPEEILTRIGSG 217
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
361-609 1.06e-13

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: 71.80  E-value: 1.06e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREgAMSEEDF---IEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFE 436
Cdd:cd06622   1 DEIEVLDELGKGNYGSVYKVLHRPTGVTmAMKEIRL-ELDESKFnqiIMELDILHKAVSPYIVDFYGAFFIEGAVYMCME 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGCLsDYL---RTQRGLFAAETLLGMCLDVCEGMAYL-EEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd06622  80 YMDAGSL-DKLyagGVATEGIPEDVLRRITYAVVKGLKFLkEEHNIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVASLA 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKfpvKWASPEVFSF------SRYSSKSDVWSFGVLMWEVfSEGKIPYENRSNSEVVEDISTGFRLYKPRLA--- 583
Cdd:cd06622 159 KTNIGCQ---SYMAPERIKSggpnqnPTYTVQSDVWSLGLSILEM-ALGRYPYPPETYANIFAQLSAIVDGDPPTLPsgy 234
                       250       260
                ....*....|....*....|....*.
gi 15718680 584 STHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd06622 235 SDDAQDFVAKCLNKIPNRRPTYAQLL 260
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
366-612 1.20e-13

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: 71.37  E-value: 1.20e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVhlgyWLNKDKVAIKT--IREGAMSEEDFIEEAEVMMKLSHPKLVQLYGV------CLEQ--------A 429
Cdd:cd14047  11 IELIGSGGFGQV----FKAKHRIDGKTyaIKRVKLNNEKAEREVKALAKLDHPNIVRYNGCwdgfdyDPETsssnssrsK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLV--FEFMEHGCLSDYLRTQRGLFAAETL-LGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM-TR 505
Cdd:cd14047  87 TKCLFiqMEFCEKGTLESWIEKRNGEKLDKVLaLEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFGLvTS 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 FVLDDQYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYEnrsNSEVVEDISTGfrlyKPRLAST 585
Cdd:cd14047 167 LKNDGKRTKSKGTL---SYMSPEQISSQDYGKEVDIYALGLILFELLHVCDSAFE---KSKFWTDLRNG----ILPDIFD 236
                       250       260       270
                ....*....|....*....|....*....|.
gi 15718680 586 HVYQIMNHCWK----ERPEDRPAFSRLLRQL 612
Cdd:cd14047 237 KRYKIEKTIIKkmlsKKPEDRPNASEILRTL 267
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
366-561 1.28e-13

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: 71.34  E-value: 1.28e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGY-WLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14662   5 VKDIGSGNFGVARLMRnKETKELVAVKYIERGLKIDENVQREIINHRSLRHPNIIRFKEVVLTPTHLAIVMEYAAGGELF 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQV--IKVSDFGMTRF-VLDDQYTSSTGTKfp 521
Cdd:cd14662  85 ERI-CNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAprLKICDFGYSKSsVLHSQPKSTVGTP-- 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 15718680 522 vKWASPEVFSFSRYSSK-SDVWSFGVLMWeVFSEGKIPYEN 561
Cdd:cd14662 162 -AYIAPEVLSRKEYDGKvADVWSCGVTLY-VMLVGAYPFED 200
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
366-556 1.33e-13

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: 71.70  E-value: 1.33e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGywLNKDK---VAIKTIR-----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd07839   5 LEKIGEGTYGTVFKA--KNRETheiVALKRVRlddddEGVPSSA--LREICLLKELKHKNIVRLYDVLHSDKKLTLVFEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfvlddqytsSTG 517
Cdd:cd07839  81 CDQD-LKKYFDSCNGDIDPEIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLAR---------AFG 150
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 15718680 518 tkFPVKWASPEV-----------FSFSRYSSKSDVWSFGVLMWEVFSEGK 556
Cdd:cd07839 151 --IPVRCYSAEVvtlwyrppdvlFGAKLYSTSIDMWSAGCIFAELANAGR 198
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
366-571 1.36e-13

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: 71.36  E-value: 1.36e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGY-WLNKDKVAIKTIREGAMSEEDFI-----EEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd05611   1 LKPISKGAFGSVYLAKkRSTGDYFAIKVLKKSDMIAKNQVtnvkaERAIMMIQGESPYVAKLYYSFQSKDYLYLVMEYLN 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGL-------FAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd05611  81 GGDCASLIKTLGGLpedwakqYIAEVVLGV--------EDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLEKRH 152
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSS-TGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPYENRSNSEVVEDI 571
Cdd:cd05611 153 NKKfVGTP---DYLAPETILGVGDDKMSDWWSLGCVIFE-FLFGYPPFHAETPDAVFDNI 208
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
369-571 1.71e-13

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: 70.76  E-value: 1.71e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVH--LGYWLNKDkVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDY 446
Cdd:cd14115   1 IGRGRFSIVKkcLHKATRKD-VAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELMDDGRLLDY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 447 LRTQRGLFaAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ---VIKVSDFGmTRFVLDDQYTSSTGTKFPvK 523
Cdd:cd14115  80 LMNHDELM-EEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIDLRIpvpRVKLIDLE-DAVQISGHRHVHHLLGNP-E 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 15718680 524 WASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14115 157 FAAPEVIQGTPVSLATDIWSIGVLTYVMLS-GVSPFLDESKEETCINV 203
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
369-571 1.94e-13

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: 70.83  E-value: 1.94e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVhlgywlnKDKVAIKTIREGAMS---------EEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFM 438
Cdd:cd14184   9 IGDGNFAVV-------KECVERSTGKEFALKiidkakccgKEHLIEnEVSILRRVKHPNIIMLIEEMDTPAELYLVMELV 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGE----NQVIKVSDFGMTRFVLDDQYTs 514
Cdd:cd14184  82 KGGDLFDAI-TSSTKYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVCEypdgTKSLKLGDFGLATVVEGPLYT- 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 515 STGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYenRSNSEVVEDI 571
Cdd:cd14184 160 VCGTP---TYVAPEIIAETGYGLKVDIWAAGVITYILLC-GFPPF--RSENNLQEDL 210
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
389-574 2.32e-13

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: 71.20  E-value: 2.32e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 389 AIKTIREgamSEEDFIEEAEVMMKL-SHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLdVC 467
Cdd:cd14178  32 AVKIIDK---SKRDPSEEIEILLRYgQHPNIITLKDVYDDGKFVYLVMELMRGGELLDRILRQKCFSEREASAVLCT-IT 107
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 468 EGMAYLEEACVIHRDLAARNCL----VGENQVIKVSDFGMTRfvlddQYTSSTGTK----FPVKWASPEVFSFSRYSSKS 539
Cdd:cd14178 108 KTVEYLHSQGVVHRDLKPSNILymdeSGNPESIRICDFGFAK-----QLRAENGLLmtpcYTANFVAPEVLKRQGYDAAC 182
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 15718680 540 DVWSFGVLMWEVFSeGKIPYENRSN---SEVVEDISTG 574
Cdd:cd14178 183 DIWSLGILLYTMLA-GFTPFANGPDdtpEEILARIGSG 219
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
364-551 2.39e-13

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: 71.19  E-value: 2.39e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQ--EIGSGQFGLVHLGYW-LNKDKVAIKTIR----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFE 436
Cdd:cd07873   3 TYIKldKLGEGTYATVYKGRSkLTDNLVALKEIRleheEGAPCTA--IREVSLLKDLKHANIVTLHDIIHTEKSLTLVFE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfvlddqytsst 516
Cdd:cd07873  81 YLDKD-LKQYLDDCGNSINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR----------- 148
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 15718680 517 GTKFPVKWASPEVFSF-----------SRYSSKSDVWSFGVLMWEV 551
Cdd:cd07873 149 AKSIPTKTYSNEVVTLwyrppdillgsTDYSTQIDMWGVGCIFYEM 194
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
358-572 2.41e-13

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: 70.52  E-value: 2.41e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 358 IDPSELtfvqeIGSGQFGLVHLG-YWLNKDKVAIKTI---REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICL 433
Cdd:cd14082   5 IFPDEV-----LGSGQFGIVYGGkHRKTGRDVAIKVIdklRFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 434 VFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ---VIKVSDFGMTRFVLDD 510
Cdd:cd14082  80 VMEKLHGDMLEMILSSEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLASAEpfpQVKLCDFGFARIIGEK 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 511 QYTSS-TGTkfPVKWAsPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYenrsNSEvvEDIS 572
Cdd:cd14082 160 SFRRSvVGT--PAYLA-PEVLRNKGYNRSLDMWSVGVIIYVSLS-GTFPF----NED--EDIN 212
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
363-602 2.94e-13

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: 70.46  E-value: 2.94e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYWLNKD-KVAIKTIREGAMSEED--------FIEEAEVMMKLS-HPKLVQLYGVCLEQAPIC 432
Cdd:cd13993   2 YQLISPIGEGAYGVVYLAVDLRTGrKYAIKCLYKSGPNSKDgndfqklpQLREIDLHRRVSrHPNIITLHDVFETEVAIY 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYLrTQRGLFAAETLL--GMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ-VIKVSDFGMTrfvLD 509
Cdd:cd13993  82 IVLEYCPNGDLFEAI-TENRIYVGKTELikNVFLQLIDAVKHCHSLGIYHRDIKPENILLSQDEgTVKLCDFGLA---TT 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTS--STGTKFpvkWASPEVFSF-----SRYSSKS-DVWSFGVLMWEVFSeGKIPYENRSNSevvEDISTGFRLYKPR 581
Cdd:cd13993 158 EKISMdfGVGSEF---YMAPECFDEvgrslKGYPCAAgDIWSLGIILLNLTF-GRNPWKIASES---DPIFYDYYLNSPN 230
                       250       260
                ....*....|....*....|....*..
gi 15718680 582 L------ASTHVYQIMNHCWKERPEDR 602
Cdd:cd13993 231 LfdvilpMSDDFYNLLRQIFTVNPNNR 257
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
477-609 2.98e-13

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 72.36  E-value: 2.98e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  477 CVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD----DQYTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVF 552
Cdd:PTZ00267 189 KMMHRDLKSANIFLMPTGIIKLGDFGFSKQYSDsvslDVASSFCGTPY---YLAPELWERKRYSKKADMWSLGVILYELL 265
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680  553 SEGKiPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:PTZ00267 266 TLHR-PFKGPSQREIMQQVLYGKYDPFPCPVSSGMKALLDPLLSKNPALRPTTQQLL 321
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
367-549 3.16e-13

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: 70.62  E-value: 3.16e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDK-VAIKTIREGAmSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 445
Cdd:cd14085   9 SELGRGATSVVYRCRQKGTQKpYAVKKLKKTV-DKKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGGELFD 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV---GENQVIKVSDFGMTRfVLDDQYTSSTGTKFPv 522
Cdd:cd14085  88 RI-VEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYatpAPDAPLKIADFGLSK-IVDQQVTMKTVCGTP- 164
                       170       180
                ....*....|....*....|....*..
gi 15718680 523 KWASPEVFSFSRYSSKSDVWSFGVLMW 549
Cdd:cd14085 165 GYCAPEILRGCAYGPEVDMWSVGVITY 191
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
355-571 3.28e-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: 70.28  E-value: 3.28e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELtfVQEIGSGQFGLVHLG-----YWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQA 429
Cdd:cd14117   2 KFTIDDFDI--GRPLGKGKFGNVYLArekqsKFIVALKVLFKSQIEKEGVEHQLRREIEIQSHLRHPNILRLYNYFHDRK 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD 509
Cdd:cd14117  80 RIYLILEYAPRGELYKELQ-KHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWSVHAPS 158
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15718680 510 DQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14117 159 LRRRTMCGT---LDYLPPEMIEGRTHDEKVDLWCIGVLCYELLV-GMPPFESASHTETYRRI 216
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
5-111 3.52e-13

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 65.65  E-value: 3.52e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680      5 ILLEEQLIKKSQQKRRtspsNFKVRFFVLTKASLAYFEDRHGKKR-TLKGSIELSRIKCVEIVKSDisiPCHYKYPFQVV 83
Cdd:smart00233   1 VIKEGWLYKKSGGGKK----SWKKRYFVLFNSTLLYYKSKKDKKSyKPKGSIDLSGCTVREAPDPD---SSKKPHCFEIK 73
                           90       100
                   ....*....|....*....|....*....
gi 15718680     84 H-DNYLLYVFAPDRESRQRWVLALKEETR 111
Cdd:smart00233  74 TsDRKTLLLQAESEEEREKWVEALRKAIA 102
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
369-564 3.77e-13

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. 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 (a pseudokinase in the case of IRAK3), 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. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 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: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 70.30  E-value: 3.77e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKdKVAIKTIREGAMSE-----EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14160   1 IGEGEIFEVYRVRIGNR-SYAVKLFKQEKKMQwkkhwKRFLSELEVLLLFQHPNILELAAYFTETEKFCLVYPYMQNGTL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGL--FAAETLLGMCLDVCEGMAYLE--EAC-VIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST-- 516
Cdd:cd14160  80 FDRLQCHGVTkpLSWHERINILIGIAKAIHYLHnsQPCtVICGNISSANILLDDQMQPKLTDFALAHFRPHLEDQSCTin 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 517 --GTKFPVKWASPEVF-SFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSN 564
Cdd:cd14160 160 mtTALHKHLWYMPEEYiRQGKLSVKTDVYSFGIVIMEVLTGCKVVLDDPKH 210
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
369-571 3.95e-13

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: 70.85  E-value: 3.95e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd05571   3 LGKGTFGKVILCREKATGELyAIKILKKEVIIAKDEVAhtltENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGGEL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQR-------GLFAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST 516
Cdd:cd05571  83 FFHLSRERvfsedrtRFYGAEIVLAL--------GYLHSQGIVYRDLKLENLLLDKDGHIKITDFGLCKEEISYGATTKT 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 517 --GTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05571 155 fcGTP---EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNRDHEVLFELI 207
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
365-556 4.00e-13

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: 70.42  E-value: 4.00e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWL-NKDKVAIKTI-----REGamseedF----IEEAEVMMKLSHPKLVQLYGVCLEQAPIC-- 432
Cdd:cd07866  12 ILGKLGEGTFGEVYKARQIkTGRVVALKKIlmhneKDG------FpitaLREIKILKKLKHPNVVPLIDMAVERPDKSkr 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 ------LVFEFMEHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF 506
Cdd:cd07866  86 krgsvyMVTPYMDHD-LSGLLENPSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARP 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15718680 507 VLDDQYTSSTG--------TKFPV-KW-ASPE-VFSFSRYSSKSDVWSFGVLMWEVFsEGK 556
Cdd:cd07866 165 YDGPPPNPKGGggggtrkyTNLVVtRWyRPPElLLGERRYTTAVDIWGIGCVFAEMF-TRR 224
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
367-572 4.11e-13

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: 70.03  E-value: 4.11e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLV-----------HLGYWLNKDKVAikTIREGaMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd14195  11 EELGSGQFAIVrkcrekgtgkeYAAKFIKKRRLS--SSRRG-VSREEIEREVNILREIQHPNIITLHDIFENKTDVVLIL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRGLFAAET--LLGMCLDvceGMAYLEEACVIHRDLAARNCLVGENQV----IKVSDFGMT-RFVL 508
Cdd:cd14195  88 ELVSGGELFDFLAEKESLTEEEAtqFLKQILD---GVHYLHSKRIAHFDLKPENIMLLDKNVpnprIKLIDFGIAhKIEA 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 509 DDQYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDIS 572
Cdd:cd14195 165 GNEFKNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGETKQETLTNIS 224
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
234-338 4.12e-13

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: 65.78  E-value: 4.12e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 234 LETYEWYNKSISRDKAEKLLLDTgKEGAFMVRDSRT-AGTYTVSVFTKAVVsennpciKHYHIKETNDNpkRYYVAEKYV 312
Cdd:cd09940   2 LSEFLWFVGEMERDTAENRLENR-PDGTYLVRVRPQgETQYALSIKYNGDV-------KHMKIEQRSDG--LYYLSESRH 71
                        90       100       110
                ....*....|....*....|....*....|.
gi 15718680 313 FDSIPLLINYHQHNG-----GGLVTRLRYPV 338
Cdd:cd09940  72 FKSLVELVNYYERNSlgenfAGLDTTLKWPY 102
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
362-618 4.18e-13

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1b, also called Activin receptor-Like Kinase 6 (ALK6), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Mutations in BMPR1b that led to inhibition of chondrogenesis can cause Brachydactyly (BD) type A2, a dominant hand malformation characterized by shortening and lateral deviation of the index fingers. A point mutation in the BMPR1b kinase domain is also associated with the Booroola phenotype, characterized by precocious differentiation of ovarian follicles. BMPR1b belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, 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, like BMPR1b, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The BMPR1b 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: 271121 [Multi-domain]  Cd Length: 305  Bit Score: 70.46  E-value: 4.18e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWlNKDKVAIK---TIREGAMSEEDFIEEAEVMmklSHPKLVQLYGVCLEQA----PICLV 434
Cdd:cd14219   6 QIQMVKQIGKGRYGEVWMGKW-RGEKVAVKvffTTEEASWFRETEIYQTVLM---RHENILGFIAADIKGTgswtQLYLI 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLE--------EACVIHRDLAARNCLVGENQVIKVSDFGM-TR 505
Cdd:cd14219  82 TDYHENGSLYDYLKSTT--LDTKAMLKLAYSSVSGLCHLHteifstqgKPAIAHRDLKSKNILVKKNGTCCIADLGLaVK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 FVLDDQ-----YTSSTGTKfpvKWASPEVF--SFSRYSSKS----DVWSFGVLMWEV---------FSEGKIPYENR-SN 564
Cdd:cd14219 160 FISDTNevdipPNTRVGTK---RYMPPEVLdeSLNRNHFQSyimaDMYSFGLILWEVarrcvsggiVEEYQLPYHDLvPS 236
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 565 SEVVEDISTGFRLYKPRLASTHVY----------QIMNHCWKERPEDRPAFSRLLRQLAEIAES 618
Cdd:cd14219 237 DPSYEDMREIVCIKRLRPSFPNRWssdeclrqmgKLMTECWAHNPASRLTALRVKKTLAKMSES 300
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
367-574 4.27e-13

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: 70.82  E-value: 4.27e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGL----VHLGYWLNkdkVAIKTIREgamSEEDFIEEAEVMMKL-SHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd14176  25 EDIGVGSYSVckrcIHKATNME---FAVKIIDK---SKRDPTEEIEILLRYgQHPNIITLKDVYDDGKYVYVVTELMKGG 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV----GENQVIKVSDFGMTRfvlddQYTSSTG 517
Cdd:cd14176  99 ELLDKILRQK-FFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYvdesGNPESIRICDFGFAK-----QLRAENG 172
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 518 TK----FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYEN---RSNSEVVEDISTG 574
Cdd:cd14176 173 LLmtpcYTANFVAPEVLERQGYDAACDIWSLGVLLYTMLT-GYTPFANgpdDTPEEILARIGSG 235
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
369-550 5.20e-13

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: 69.95  E-value: 5.20e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLgyWLNKD---KVAIKTIRE--GAMSEEDFIEEAEVMMKLSHPKLVQLYGV------CLEQAPIcLVFEF 437
Cdd:cd14039   1 LGTGGFGNVCL--YQNQEtgeKIAIKSCRLelSVKNKDRWCHEIQIMKKLNHPNVVKACDVpeemnfLVNDVPL-LAMEY 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQR---GLFAAEtLLGMCLDVCEGMAYLEEACVIHRDLAARNCL---VGENQVIKVSDFGMTRFVldDQ 511
Cdd:cd14039  78 CSGGDLRKLLNKPEnccGLKESQ-VLSLLSDIGSGIQYLHENKIIHRDLKPENIVlqeINGKIVHKIIDLGYAKDL--DQ 154
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 15718680 512 ---YTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd14039 155 gslCTSFVGT---LQYLAPELFENKSYTVTVDYWSFGTMVFE 193
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
406-602 5.65e-13

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: 70.09  E-value: 5.65e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 406 EAEVMMKLSHPKLVQLYG-VCLEQAPICLVFEFMEHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEE--ACVIHRD 482
Cdd:cd14041  60 EYRIHKELDHPRIVKLYDyFSLDTDSFCTVLEYCEGNDLDFYLK-QHKLMSEKEARSIIMQIVNALKYLNEikPPIIHYD 138
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 483 LAARNCLVGENQV---IKVSDFGMTRFVLDDQYTSSTGTKFPVKWAS------PEVFSFS----RYSSKSDVWSFGVLMW 549
Cdd:cd14041 139 LKPGNILLVNGTAcgeIKITDFGLSKIMDDDSYNSVDGMELTSQGAGtywylpPECFVVGkeppKISNKVDVWSVGVIFY 218
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 550 EVFSeGKIPY-ENRSNSEVVED----ISTGFRLYKPRLASTHVYQIMNHCWKERPEDR 602
Cdd:cd14041 219 QCLY-GRKPFgHNQSQQDILQEntilKATEVQFPPKPVVTPEAKAFIRRCLAYRKEDR 275
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
368-573 6.05e-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: 6.05e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 368 EIGSGQFGLVHLGYwlNKD-------KVAIKT--IREGAMSE------------------EDFIEEAEVMMKLSHPKLVQ 420
Cdd:cd14118   1 EIGKGSYGIVKLAY--NEEdntlyamKILSKKklLKQAGFFRrppprrkpgalgkpldplDRVYREIAILKKLDHPNVVK 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 421 LYGVCLEQAP--ICLVFEFMEHGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKV 498
Cdd:cd14118  79 LVEVLDDPNEdnLYMVFELVDKGAVMEVPTDNP--LSEETARSYFRDIVLGIEYLHYQKIIHRDIKPSNLLLGDDGHVKI 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 499 SDFGMT-RFVLDDQYTSST-GTkfPVKWAsPEVFSFSR--YSSKS-DVWSFGVLMWeVFSEGKIPYENRSNSEVVEDIST 573
Cdd:cd14118 157 ADFGVSnEFEGDDALLSSTaGT--PAFMA-PEALSESRkkFSGKAlDIWAMGVTLY-CFVFGRCPFEDDHILGLHEKIKT 232
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
367-574 6.97e-13

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: 69.58  E-value: 6.97e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDKV-AIKTIREgamSEEDFIEEAEVMMKLS-HPKLVQLYGVCLEQAPICLVFEFMEHGCLS 444
Cdd:cd14091   6 EEIGKGSYSVCKRCIHKATGKEyAVKIIDK---SKRDPSEEIEILLRYGqHPNIITLRDVYDDGNSVYLVTELLRGGELL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLFAAETLLGMCLdVCEGMAYLEEACVIHRDLAARNCLV----GENQVIKVSDFGMTRFVLDDQ-------YT 513
Cdd:cd14091  83 DRILRQKFFSEREASAVMKT-LTKTVEYLHSQGVVHRDLKPSNILYadesGDPESLRICDFGFAKQLRAENgllmtpcYT 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 514 SStgtkfpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSN---SEVVEDISTG 574
Cdd:cd14091 162 AN--------FVAPEVLKKQGYDAACDIWSLGVLLYTMLA-GYTPFASGPNdtpEVILARIGSG 216
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
366-552 7.87e-13

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: 69.22  E-value: 7.87e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGY-WLNKDKVAIKTIREGAMSEEDF--IEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMeHGC 442
Cdd:cd07870   5 LEKLGEGSYATVYKGIsRINGQLVALKVISMKTEEGVPFtaIREASLLKGLKHANIVLLHDIIHTKETLTFVFEYM-HTD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF--VLDDQYTSSTGTkf 520
Cdd:cd07870  84 LAQYMIQHPGGLHPYNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLARAksIPSQTYSSEVVT-- 161
                       170       180       190
                ....*....|....*....|....*....|....
gi 15718680 521 pvKWASPE--VFSFSRYSSKSDVWSFGVLMWEVF 552
Cdd:cd07870 162 --LWYRPPdvLLGATDYSSALDIWGAGCIFIEML 193
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
369-595 7.96e-13

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: 69.17  E-value: 7.96e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLN-KDKVAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME---- 439
Cdd:cd05579   1 ISRGAYGRVYLAKKKStGDLYAIKVIKKRDMIRKNQVDsvlaERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPggdl 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 ------HGCLSDYLRTQrglFAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF-VLDDQY 512
Cdd:cd05579  81 ysllenVGALDEDVARI---YIAEIVLAL--------EYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKVgLVRRQI 149
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTKFPVK-------------WASPEVFSFSRYSSKSDVWSFGVLMWEVFS------------------EGKIPYEN 561
Cdd:cd05579 150 KLSIQKKSNGApekedrrivgtpdYLAPEILLGQGHGKTVDWWSLGVILYEFLVgippfhaetpeeifqnilNGKIEWPE 229
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 15718680 562 RSN-SEVVEDISTGFRLYKP--RLASTHVYQIMNHCW 595
Cdd:cd05579 230 DPEvSDEAKDLISKLLTPDPekRLGAKGIEEIKNHPF 266
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
366-553 8.46e-13

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: 69.64  E-value: 8.46e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYW-LNKDKVAIKTIR----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd07872  11 LEKLGEGTYATVFKGRSkLTENLVALKEIRleheEGAPCTA--IREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEYLDK 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfvLDDQYTSSTGTKF 520
Cdd:cd07872  89 D-LKQYMDDCGNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR--AKSVPTKTYSNEV 165
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15718680 521 PVKWASPE--VFSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd07872 166 VTLWYRPPdvLLGSSEYSTQIDMWGVGCIFFEMAS 200
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
362-602 9.25e-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: 70.05  E-value: 9.25e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLS-HPKLVQLYGVCLEQAPICLVF 435
Cdd:cd05617  16 DFDLIRVIGRGSYAKVLLVRLKKNDQIyAMKVVKKELVHDDEDIDwvqtEKHVFEQASsNPFLVGLHSCFQTTSRLFLVI 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd05617  96 EYVNGGDLMFHMQRQRKL-PEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTS 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 516 TGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSevvEDISTGFRLYK---------PRLASTH 586
Cdd:cd05617 175 TFCGTP-NYIAPEILRGEEYGFSVDWWALGVLMFEMMA-GRSPFDIITDN---PDMNTEDYLFQvilekpiriPRFLSVK 249
                       250
                ....*....|....*.
gi 15718680 587 VYQIMNHCWKERPEDR 602
Cdd:cd05617 250 ASHVLKGFLNKDPKER 265
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
362-574 9.42e-13

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: 69.39  E-value: 9.42e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWLNKD--KVAIKTIREGAMSEEDF--------IEEAEVMMKLSHPKLVQLYGVCLEQAPI 431
Cdd:cd14096   2 NYRLINKIGEGAFSNVYKAVPLRNTgkPVAIKVVRKADLSSDNLkgssraniLKEVQIMKRLSHPNIVKLLDFQESDEYY 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 CLVFEFMEHGCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV--------------------- 490
Cdd:cd14096  82 YIVLELADGGEIFHQI-VRLTYFSEDLSRHVITQVASAVKYLHEIGVVHRDIKPENLLFepipfipsivklrkadddetk 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 491 ------------GENQVIKVSDFGMTRFVLDDQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIP 558
Cdd:cd14096 161 vdegefipgvggGGIGIVKLADFGLSKQVWDSNTKTPCGT---VGYTAPEVVKDERYSKKVDMWALGCVLYTLLC-GFPP 236
                       250
                ....*....|....*.
gi 15718680 559 YENRSNSEVVEDISTG 574
Cdd:cd14096 237 FYDESIETLTEKISRG 252
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
369-602 1.01e-12

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: 69.35  E-value: 1.01e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLN-KDK---VAIKTIREGAMSEEDFIE---EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd05582   3 LGQGSFGKVFLVRKITgPDAgtlYAMKVLKKATLKVRDRVRtkmERDILADVNHPFIVKLHYAFQTEGKLYLILDFLRGG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CL-----SDYLRTQRG--LFAAEtlLGMCLDvcegmaYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYT- 513
Cdd:cd05582  83 DLftrlsKEVMFTEEDvkFYLAE--LALALD------HLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHEKKa 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 -SSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfRLYKPRLASTHVYQIMN 592
Cdd:cd05582 155 ySFCGT---VEYMAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPFQGKDRKETMTMILKA-KLGMPQFLSPEAQSLLR 229
                       250
                ....*....|
gi 15718680 593 HCWKERPEDR 602
Cdd:cd05582 230 ALFKRNPANR 239
STKc_PIM2 cd14101
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
369-609 1.02e-12

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 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: 271003 [Multi-domain]  Cd Length: 257  Bit Score: 68.34  E-value: 1.02e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWL-NKDKVAIKTIREGAMSEEDFIE-------EAEVMMKL----SHPKLVQLYGVCLEQAPICLVFE 436
Cdd:cd14101   8 LGKGGFGTVYAGHRIsDGLQVAIKQISRNRVQQWSKLPgvnpvpnEVALLQSVgggpGHRGVIRLLDWFEIPEGFLLVLE 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHgC--LSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVG-ENQVIKVSDFGMTRFVLDDQYT 513
Cdd:cd14101  88 RPQH-CqdLFDYI-TERGALDESLARRFFKQVVEAVQHCHSKGVVHRDIKDENILVDlRTGDIKLIDFGSGATLKDSMYT 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 514 SSTGTKFpvkWASPEVFSFSRYSS-KSDVWSFGVLMWEVFSeGKIPYENrsNSEVVEDistgfRLYKPRLASTHVYQIMN 592
Cdd:cd14101 166 DFDGTRV---YSPPEWILYHQYHAlPATVWSLGILLYDMVC-GDIPFER--DTDILKA-----KPSFNKRVSNDCRSLIR 234
                       250
                ....*....|....*..
gi 15718680 593 HCWKERPEDRPAFSRLL 609
Cdd:cd14101 235 SCLAYNPSDRPSLEQIL 251
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
362-602 1.02e-12

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: 69.67  E-value: 1.02e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVhlgyWLNKDKV-----AIKTIREGAMSEED----FIEEAEVMMKLSHPKLVQLYGVCLEQAPIC 432
Cdd:cd05594  26 DFEYLKLLGKGTFGKV----ILVKEKAtgryyAMKILKKEVIVAKDevahTLTENRVLQNSRHPFLTALKYSFQTHDRLC 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLE-EACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQ 511
Cdd:cd05594 102 FVMEYANGGELFFHLSRER-VFSEDRARFYGAEIVSALDYLHsEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDG 180
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 512 YTSSTGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfRLYKPRLASTHVYQIM 591
Cdd:cd05594 181 ATMKTFCGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHEKLFELILME-EIRFPRTLSPEAKSLL 257
                       250
                ....*....|.
gi 15718680 592 NHCWKERPEDR 602
Cdd:cd05594 258 SGLLKKDPKQR 268
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
406-553 1.03e-12

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 69.90  E-value: 1.03e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  406 EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAA 485
Cdd:PHA03209 107 EAMLLQNVNHPSVIRMKDTLVSGAITCMVLPHYSSD-LYTYLTKRSRPLPIDQALIIEKQILEGLRYLHAQRIIHRDVKT 185
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680  486 RNCLVGENQVIKVSDFGMTRF-VLDDQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:PHA03209 186 ENIFINDVDQVCIGDLGAAQFpVVAPAFLGLAGT---VETNAPEVLARDKYNSKADIWSAGIVLFEMLA 251
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
367-573 1.14e-12

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: 68.44  E-value: 1.14e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLV-----------HLGYWLNKDKVaiKTIREGAMSEEdfIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLV 434
Cdd:cd14196  11 EELGSGQFAIVkkcrekstgleYAAKFIKKRQS--RASRRGVSREE--IErEVSILRQVLHPNIITLHDVYENRTDVVLI 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQV----IKVSDFGMTRFVLDD 510
Cdd:cd14196  87 LELVSGGELFDFL-AQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIpiphIKLIDFGLAHEIEDG 165
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 511 -QYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDIST 573
Cdd:cd14196 166 vEFKNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETLANITA 225
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
362-591 1.17e-12

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 69.62  E-value: 1.17e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  362 ELTFVQEIGSGQFGLVHLGYWLNKD--KVAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:PTZ00426  31 DFNFIRTLGTGSFGRVILATYKNEDfpPVAIKRFEKSKIIKQKQVDhvfsERKILNYINHPFCVNLYGSFKDESYLYLVL 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  436 EFMEHGCLSDYLRTQR------GLFAAETLLGMcldvcegMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD 509
Cdd:PTZ00426 111 EFVIGGEFFTFLRRNKrfpndvGCFYAAQIVLI-------FEYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKVVDT 183
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  510 DQYTsSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFrLYKPRLASTHVYQ 589
Cdd:PTZ00426 184 RTYT-LCGTP---EYIAPEILLNVGHGKAADWWTLGIFIYEILV-GCPPFYANEPLLIYQKILEGI-IYFPKFLDNNCKH 257

                 ..
gi 15718680  590 IM 591
Cdd:PTZ00426 258 LM 259
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
369-561 1.26e-12

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 69.40  E-value: 1.26e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  369 IGSGQFGLVHLGYWLNKDK-VAIKTIREGAMSEEDF---------------IEEAEVMMKLSHPKLVQLYGVCLEQAPIC 432
Cdd:PTZ00024  17 LGEGTYGKVEKAYDTLTGKiVAIKKVKIIEISNDVTkdrqlvgmcgihfttLRELKIMNEIKHENIMGLVDVYVEGDFIN 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  433 LVFEFMEhgclSDYlrtqRGLFAAETLLG------MCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR- 505
Cdd:PTZ00024  97 LVMDIMA----SDL----KKVVDRKIRLTesqvkcILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLARr 168
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15718680  506 FVLDDQYTSSTGTKFPVK------------WASPE-VFSFSRYSSKSDVWSFGVLMWEVFSeGK--IPYEN 561
Cdd:PTZ00024 169 YGYPPYSDTLSKDETMQRreemtskvvtlwYRAPElLMGAEKYHFAVDMWSVGCIFAELLT-GKplFPGEN 238
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
369-574 1.43e-12

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: 69.06  E-value: 1.43e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGywLNK---DKVAIKTIREGAM--SEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP--ICLVFEFMEHG 441
Cdd:cd13988   1 LGQGATANVFRG--RHKktgDLYAVKVFNNLSFmrPLDVQMREFEVLKKLNHKNIVKLFAIEEELTTrhKVLVMELCPCG 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLR---TQRGLFAAETLLgMCLDVCEGMAYLEEACVIHRDLAARNCL--VGEN--QVIKVSDFGMTRFVLDD-QYT 513
Cdd:cd13988  79 SLYTVLEepsNAYGLPESEFLI-VLRDVVAGMNHLRENGIVHRDIKPGNIMrvIGEDgqSVYKLTDFGAARELEDDeQFV 157
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 514 SSTGTKfpvKWASPEVFSFS--------RYSSKSDVWSFGVLMWEVfSEGKIPYE----NRSNSEVVEDISTG 574
Cdd:cd13988 158 SLYGTE---EYLHPDMYERAvlrkdhqkKYGATVDLWSIGVTFYHA-ATGSLPFRpfegPRRNKEVMYKIITG 226
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
235-337 1.47e-12

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: 63.89  E-value: 1.47e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 235 ETYEWYNKSISRDKAEK-LLLDTGKEGAFMVRDSRTA-GTYTVSVftKAVVSENNpCIKHYHIKETNDNPkrYYVAEKYV 312
Cdd:cd10371   1 EVEKWFFRTISRKDAERqLLAPMNKAGSFLIRESESNkGAFSLSV--KDVTTQGE-VVKHYKIRSLDNGG--YYISPRIT 75
                        90       100
                ....*....|....*....|....*
gi 15718680 313 FDSIPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd10371  76 FPTLQALVQHYSKKGDGLCQKLTLP 100
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
235-337 1.50e-12

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: 64.12  E-value: 1.50e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 235 ETYEWYNKSISRDKAEKLLLDTGK-EGAFMVRDSRT-AGTYTVSVftKAVVSENNPCIKHYHIKetNDNPKRYYVAEKYV 312
Cdd:cd10362   1 EPEPWFFKNLSRNDAERQLLAPGNtHGSFLIRESETtAGSFSLSV--RDFDQNQGEVVKHYKIR--NLDNGGFYISPRIT 76
                        90       100
                ....*....|....*....|....*
gi 15718680 313 FDSIPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd10362  77 FPGLHELVRHYTNASDGLCTRLSRP 101
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
367-549 1.66e-12

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: 68.60  E-value: 1.66e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWL-NKDKVAIKTIREGAMSEEDF--IE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd14086   7 EELGKGAFSVVRRCVQKsTGQEFAAKIINTKKLSARDHqkLErEARICRLLKHPNIVRLHDSISEEGFHYLVFDLVTGGE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRglFAAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVG---ENQVIKVSDFGMTRFVLDDQ--YTSST 516
Cdd:cd14086  87 LFEDIVARE--FYSEADASHCIqQILESVNHCHQNGIVHRDLKPENLLLAsksKGAAVKLADFGLAIEVQGDQqaWFGFA 164
                       170       180       190
                ....*....|....*....|....*....|...
gi 15718680 517 GTkfPVkWASPEVFSFSRYSSKSDVWSFGVLMW 549
Cdd:cd14086 165 GT--PG-YLSPEVLRKDPYGKPVDIWACGVILY 194
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
175-225 2.02e-12

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 62.10  E-value: 2.02e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 175 VVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSY 225
Cdd:cd00174   1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGREGLFPANY 51
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
366-551 2.11e-12

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: 68.18  E-value: 2.11e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYW-LNKDKVAIKTIRegaMSEED-----FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMe 439
Cdd:cd07869  10 LEKLGEGSYATVYKGKSkVNGKLVALKVIR---LQEEEgtpftAIREASLLKGLKHANIVLLHDIIHTKETLTLVFEYV- 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSStgTK 519
Cdd:cd07869  86 HTDLCQYMDKHPGGLHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLARAKSVPSHTYS--NE 163
                       170       180       190
                ....*....|....*....|....*....|....
gi 15718680 520 FPVKWASPE--VFSFSRYSSKSDVWSFGVLMWEV 551
Cdd:cd07869 164 VVTLWYRPPdvLLGSTEYSTCLDMWGVGCIFVEM 197
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
363-609 2.38e-12

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 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: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 67.77  E-value: 2.38e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGywLNKD---KVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLY----GVCLEQAPIC 432
Cdd:cd14030  27 LKFDIEIGRGSFKTVYKG--LDTEttvEVAWCELQDRKLSKSErqrFKEEAGMLKGLQHPNIVRFYdsweSTVKGKKCIV 104
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 433 LVFEFMEHGCLSDYLRTQRgLFAAETLLGMCLDVCEGMAYLEEAC--VIHRDLAARNCLV-GENQVIKVSDFGMTRFVLD 509
Cdd:cd14030 105 LVTELMTSGTLKTYLKRFK-VMKIKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATLKRA 183
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 DQYTSSTGTKfpvKWASPEVFSfSRYSSKSDVWSFGVLMWEVfSEGKIPY-ENRSNSEVVEDISTGFrlyKP----RLAS 584
Cdd:cd14030 184 SFAKSVIGTP---EFMAPEMYE-EKYDESVDVYAFGMCMLEM-ATSEYPYsECQNAAQIYRRVTSGV---KPasfdKVAI 255
                       250       260
                ....*....|....*....|....*
gi 15718680 585 THVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd14030 256 PEVKEIIEGCIRQNKDERYAIKDLL 280
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
369-602 2.48e-12

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: 68.16  E-value: 2.48e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEED---------FIEEAEVMMKLSHPKLVQLYG-VCLEQAPICLVFEFM 438
Cdd:cd14040  14 LGRGGFSEVYKAFDLYEQRYAAVKIHQLNKSWRDekkenyhkhACREYRIHKELDHPRIVKLYDyFSLDTDTFCTVLEYC 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEE--ACVIHRDLAARNCLVGENQV---IKVSDFGMTRFVLDDQY- 512
Cdd:cd14040  94 EGNDLDFYLK-QHKLMSEKEARSIVMQIVNALRYLNEikPPIIHYDLKPGNILLVDGTAcgeIKITDFGLSKIMDDDSYg 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 -------TSSTGTKFpvkWASPEVFSFSR----YSSKSDVWSFGVLMWEVFSeGKIPY-ENRSNSEVVED----ISTGFR 576
Cdd:cd14040 173 vdgmdltSQGAGTYW---YLPPECFVVGKeppkISNKVDVWSVGVIFFQCLY-GRKPFgHNQSQQDILQEntilKATEVQ 248
                       250       260
                ....*....|....*....|....*.
gi 15718680 577 LYKPRLASTHVYQIMNHCWKERPEDR 602
Cdd:cd14040 249 FPVKPVVSNEAKAFIRRCLAYRKEDR 274
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
365-551 2.49e-12

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: 67.75  E-value: 2.49e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDKVA-IKTIREGAMSEEDFIEEAEVMMK-LSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd06646  13 LIQRVGSGTYGDVYKARNLHTGELAaVKIIKLEPGDDFSLIQQEIFMVKeCKHCNIVAYFGSYLSREKLWICMEYCGGGS 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDD--QYTSSTGTKF 520
Cdd:cd06646  93 LQDIYHVT-GPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKITATiaKRKSFIGTPY 171
                       170       180       190
                ....*....|....*....|....*....|....
gi 15718680 521 pvkWASPEVFSFSR---YSSKSDVWSFGVLMWEV 551
Cdd:cd06646 172 ---WMAPEVAAVEKnggYNQLCDIWAVGITAIEL 202
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
361-553 2.54e-12

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: 67.68  E-value: 2.54e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFglvhlgywlnkdkVAIKTIREGAMSEEDFIEEAEV--MMKLS-HPKLVQLYGVCLEQAPIC--LVF 435
Cdd:cd07831  13 SEVLKAQSRKTGKY-------------YAIKCMKKHFKSLEQVNNLREIqaLRRLSpHPNILRLIEVLFDRKTGRlaLVF 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEhGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENqVIKVSDFGMTRFVLDDQ-YTS 514
Cdd:cd07831  80 ELMD-MNLYELIKGRKRPLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKDD-ILKLADFGSCRGIYSKPpYTE 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 15718680 515 STGTKFpvkWASPE-VFSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd07831 158 YISTRW---YRAPEcLLTDGYYGPKMDIWAVGCVFFEILS 194
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
369-571 2.63e-12

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: 68.18  E-value: 2.63e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVM-MKLSHPKLVQLYgvCLEQAPICLVF--EFMEH 440
Cdd:cd05592   3 LGKGSFGKVMLAELKGTNQYfAIKALKKDVVLEDDDVEctmiERRVLaLASQHPFLTHLF--CTFQTESHLFFvmEYLNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRtQRGLF--------AAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd05592  81 GDLMFHIQ-QSGRFdedrarfyGAEIICGL--------QFLHSRGIIYRDLKLDNVLLDREGHIKIADFGMCKENIYGEN 151
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15718680 513 TSST--GTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05592 152 KASTfcGTP---DYIAPEILKGQKYNQSVDWWSFGVLLYEMLI-GQSPFHGEDEDELFWSI 208
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
365-571 3.08e-12

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: 68.47  E-value: 3.08e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVhlgyWLNKDK-----VAIKTIREGAMSEED----FIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:cd05573   5 VIKVIGRGAFGEV----WLVRDKdtgqvYAMKILRKSDMLKREqiahVRAERDILADADSPWIVRLHYAFQDEDHLYLVM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEHGCLSDYLrTQRGLF--------AAETLLGmcLDVCEGMAYleeacvIHRDLAARNCLVGENQVIKVSDFGM---- 503
Cdd:cd05573  81 EYMPGGDLMNLL-IKYDVFpeetarfyIAELVLA--LDSLHKLGF------IHRDIKPDNILLDADGHIKLADFGLctkm 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 504 -----TRFVLDDQYTSSTGTKFPVKWA-------------------SPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPY 559
Cdd:cd05573 152 nksgdRESYLNDSVNTLFQDNVLARRRphkqrrvraysavgtpdyiAPEVLRGTGYGPECDWWSLGVILYEMLY-GFPPF 230
                       250
                ....*....|..
gi 15718680 560 ENRSNSEVVEDI 571
Cdd:cd05573 231 YSDSLVETYSKI 242
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
353-562 3.27e-12

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: 67.52  E-value: 3.27e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 353 YGKWVIDpsELTFVQEIGSGQFGLVHLGywlnKDK-----VAIKTIREGAmSEEDF----IEEAEVMMKLSHPKLVQLYG 423
Cdd:cd07864   1 WGKRCVD--KFDIIGIIGEGTYGQVYKA----KDKdtgelVALKKVRLDN-EKEGFpitaIREIKILRQLNHRSVVNLKE 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 424 VCL----------EQAPICLVFEFMEHGcLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGEN 493
Cdd:cd07864  74 IVTdkqdaldfkkDKGAFYLVFEYMDHD-LMGLLESGLVHFSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNK 152
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 494 QVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPE-VFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENR 562
Cdd:cd07864 153 GQIKLADFGLARLYNSEESRPYTNKVITLWYRPPElLLGEERYGPAIDVWSCGCILGELFTKKPIFQANQ 222
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
366-609 3.56e-12

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: 67.39  E-value: 3.56e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGywlnKDKV-----AIKTI--REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFM 438
Cdd:cd14046  11 LQVLGKGAFGQVVKV----RNKLdgryyAIKKIklRSESKNNSRILREVMLLSRLNHQHVVRYYQAWIERANLYIQMEYC 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 EHGCLSDYLRTqrGLFAAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGM-------------- 503
Cdd:cd14046  87 EKSTLRDLIDS--GLFQDTDRLWRLFrQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLatsnklnvelatqd 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 504 ------TRFVLDDQYTSSTGTKFPVkwaSPEVFS--FSRYSSKSDVWSFGVL---MWEVFSEGkipYEnRSNsevvedIS 572
Cdd:cd14046 165 inkstsAALGSSGDLTGNVGTALYV---APEVQSgtKSTYNEKVDMYSLGIIffeMCYPFSTG---ME-RVQ------IL 231
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 15718680 573 TGFRLYKPRLASTHVYQIMNHCWK-------ERPEDRPAFSRLL 609
Cdd:cd14046 232 TALRSVSIEFPPDFDDNKHSKQAKlirwllnHDPAKRPSAQELL 275
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
344-602 3.58e-12

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: 68.14  E-value: 3.58e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 344 KAPVTAGLRygkwvidpsELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLS-HPK 417
Cdd:cd05618  12 KASSSLGLQ---------DFDLLRVIGRGSYAKVLLVRLKKTERIyAMKVVKKELVNDDEDIDwvqtEKHVFEQASnHPF 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 418 LVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIK 497
Cdd:cd05618  83 LVGLHSCFQTESRLFFVIEYVNGGDLMFHMQRQRKL-PEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIK 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 498 VSDFGMTRFVLDDQYTSSTGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGF-- 575
Cdd:cd05618 162 LTDYGMCKEGLRPGDTTSTFCGTP-NYIAPEILRGEDYGFSVDWWALGVLMFEMMA-GRSPFDIVGSSDNPDQNTEDYlf 239
                       250       260       270
                ....*....|....*....|....*....|...
gi 15718680 576 ------RLYKPRLASTHVYQIMNHCWKERPEDR 602
Cdd:cd05618 240 qvilekQIRIPRSLSVKAASVLKSFLNKDPKER 272
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
364-560 3.84e-12

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: 66.81  E-value: 3.84e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYWLN-KDKVAIKTIREGAMSEeDFIE-----EAEVMMKLSHPKLVQLYGvCLEQA--PICLVF 435
Cdd:cd14164   3 TLGTTIGEGSFSKVKLATSQKyCCKVAIKIVDRRRASP-DFVQkflprELSILRRVNHPNIVQMFE-CIEVAngRLYIVM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEhgclSDYLRT--QRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV-GENQVIKVSDFGMTRFVLDDQY 512
Cdd:cd14164  81 EAAA----TDLLQKiqEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLsADDRKIKIADFGFARFVEDYPE 156
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 513 TSST--GTKfpvKWASPEVFSFSRYSSKS-DVWSFGVLMWeVFSEGKIPYE 560
Cdd:cd14164 157 LSTTfcGSR---AYTPPEVILGTPYDPKKyDVWSLGVVLY-VMVTGTMPFD 203
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
369-549 4.57e-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: 66.94  E-value: 4.57e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREG-AMSEEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 445
Cdd:cd14183  14 IGDGNFAVVKECVERSTGREyALKIINKSkCRGKEHMIQnEVSILRRVKHPNIVLLIEEMDMPTELYLVMELVKGGDLFD 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 446 YLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQ----VIKVSDFGMTRFVLDDQYTsSTGTKfp 521
Cdd:cd14183  94 AI-TSTNKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVYEHQdgskSLKLGDFGLATVVDGPLYT-VCGTP-- 169
                       170       180
                ....*....|....*....|....*...
gi 15718680 522 vKWASPEVFSFSRYSSKSDVWSFGVLMW 549
Cdd:cd14183 170 -TYVAPEIIAETGYGLKVDIWAAGVITY 196
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
239-338 4.65e-12

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: 62.84  E-value: 4.65e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 239 WYNKSISRDKAEKLLLDTGKEGAFMVRDSRT-AGTYTVSVFtkavvseNNPCIKHYHIKETNDN----------PKRYyv 307
Cdd:cd10343   5 WYHGNITRSKAEELLSKAGKDGSFLVRDSESvSGAYALCVL-------YQNCVHTYRILPNAEDklsvqasegvPVRF-- 75
                        90       100       110
                ....*....|....*....|....*....|.
gi 15718680 308 aekyvFDSIPLLINYHQHNGGGLVTRLRYPV 338
Cdd:cd10343  76 -----FTTLPELIEFYQKENMGLVTHLLYPV 101
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
389-574 5.28e-12

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: 66.96  E-value: 5.28e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 389 AIKTIREgamSEEDFIEEAEVMMKL-SHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRgLFAAETLLGMCLDVC 467
Cdd:cd14177  33 AVKIIDK---SKRDPSEEIEILMRYgQHPNIITLKDVYDDGRYVYLVTELMKGGELLDRILRQK-FFSEREASAVLYTIT 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 468 EGMAYLEEACVIHRDLAARNCLV----GENQVIKVSDFGMTRFVLDDQYTSSTGTkFPVKWASPEVFSFSRYSSKSDVWS 543
Cdd:cd14177 109 KTVDYLHCQGVVHRDLKPSNILYmddsANADSIRICDFGFAKQLRGENGLLLTPC-YTANFVAPEVLMRQGYDAACDIWS 187
                       170       180       190
                ....*....|....*....|....*....|....
gi 15718680 544 FGVLMWEVFSeGKIPYENRSN---SEVVEDISTG 574
Cdd:cd14177 188 LGVLLYTMLA-GYTPFANGPNdtpEEILLRIGSG 220
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
369-571 5.35e-12

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: 67.13  E-value: 5.35e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVM-MKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd05591   3 LGKGSFGKVMLAERKGTDEVyAIKVLKKDVILQDDDVDctmtEKRILaLAAKHPFLTALHSCFQTKDRLFFVMEYVNGGD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGL-------FAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd05591  83 LMFQIQRARKFdeprarfYAAEVTLAL--------MFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKEGILNGKTTT 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 516 TGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05591 155 TFCGTP-DYIAPEILQELEYGPSVDWWALGVLMYEMMA-GQPPFEADNEDDLFESI 208
PHA02988 PHA02988
hypothetical protein; Provisional
384-612 5.71e-12

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 66.69  E-value: 5.71e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  384 NKDKVAIKTIREGAMSE----EDFIEEAEVMMKLSHPKLVQLYG----VCLEQAPICLVFEFMEHGCLSDYLRTQRGLfA 455
Cdd:PHA02988  42 NNKEVIIRTFKKFHKGHkvliDITENEIKNLRRIDSNNILKIYGfiidIVDDLPRLSLILEYCTRGYLREVLDKEKDL-S 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  456 AETLLGMCLDVCEGMAYLEEAC-VIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGtkfpVKWASPEVFS--F 532
Cdd:PHA02988 121 FKTKLDMAIDCCKGLYNLYKYTnKPYKNLTSVSFLVTENYKLKIICHGLEKILSSPPFKNVNF----MVYFSYKMLNdiF 196
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  533 SRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVED-ISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:PHA02988 197 SEYTIKDDIYSLGVVLWEIFT-GKIPFENLTTKEIYDLiINKNNSLKLPLDCPLEIKCIVEACTSHDSIKRPNIKEILYN 275

                 .
gi 15718680  612 L 612
Cdd:PHA02988 276 L 276
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
369-560 6.25e-12

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: 66.19  E-value: 6.25e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLG-YWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLS-HPKLVQLYGVCLEqAPICLVF--EFMEHGCLS 444
Cdd:cd13987   1 LGEGTYGKVLLAvHKGSGTKMALKFVPKPSTKLKDFLREYNISLELSvHPHIIKTYDVAFE-TEDYYVFaqEYAPYGDLF 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLfaAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLV--GENQVIKVSDFGMTRfvlddqytsSTGTKFP 521
Cdd:cd13987  80 SIIPPQVGL--PEERVKRCAaQLASALDFMHSKNLVHRDIKPENVLLfdKDCRRVKLCDFGLTR---------RVGSTVK 148
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 522 VKWAS-----PEVFSFSRYSS-----KSDVWSFGVLMWEVFSeGKIPYE 560
Cdd:cd13987 149 RVSGTipytaPEVCEAKKNEGfvvdpSIDVWAFGVLLFCCLT-GNFPWE 196
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
369-563 7.13e-12

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; 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. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 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: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 66.40  E-value: 7.13e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKVaIKTIREGAMSEEDFIE-----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14157   1 ISEGTFADIYKGYRHGKQYV-IKRLKETECESPKSTErffqtEVQICFRCCHPNILPLLGFCVESDCHCLIYPYMPNGSL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRG--LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMtRFVLDDQYTSSTGTKFP 521
Cdd:cd14157  80 QDRLQQQGGshPLPWEQRLSISLGLLKAVQHLHNFGILHGNIKSSNVLLDGNLLPKLGHSGL-RLCPVDKKSVYTMMKTK 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 522 VKWAS----PEvfSFSRY---SSKSDVWSFGVLMWEVFSEGKIPYENRS 563
Cdd:cd14157 159 VLQISlaylPE--DFVRHgqlTEKVDIFSCGVVLAEILTGIKAMDEFRS 205
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
366-550 7.84e-12

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 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: 270842 [Multi-domain]  Cd Length: 336  Bit Score: 67.01  E-value: 7.84e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGY-WLNKDKVAIKTIR---EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAP------ICLVF 435
Cdd:cd07855  10 IETIGSGAYGVVCSAIdTKSGQKVAIKKIPnafDVVTTAKRTLRELKILRHFKHDNIIAIRDILRPKVPyadfkdVYVVL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 436 EFMEhGCLSDYLRTQRGLFAAET--LLGMCLdvcEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR----FVLD 509
Cdd:cd07855  90 DLME-SDLHHIIHSDQPLTLEHIryFLYQLL---RGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARglctSPEE 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 15718680 510 DQY--TSSTGTKFpvkWASPEV-FSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd07855 166 HKYfmTEYVATRW---YRAPELmLSLPEYTQAIDMWSVGCIFAE 206
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
361-559 8.13e-12

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 67.16  E-value: 8.13e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  361 SELTFVQEIGSGQFGLV----HLG----------YWLNKDKVAIKTIREgamseedfieeAEVMMKLSHPKLVQLYGVCL 426
Cdd:PLN00034  74 SELERVNRIGSGAGGTVykviHRPtgrlyalkviYGNHEDTVRRQICRE-----------IEILRDVNHPNVVKCHDMFD 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  427 EQAPICLVFEFMEHGCLSDylrtqRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF 506
Cdd:PLN00034 143 HNGEIQVLLEFMDGGSLEG-----THIADEQFLADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRI 217
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  507 VLD--DQYTSSTGTkfpVKWASPEV----FSFSRYSSKS-DVWSFGVLMWEvFSEGKIPY 559
Cdd:PLN00034 218 LAQtmDPCNSSVGT---IAYMSPERintdLNHGAYDGYAgDIWSLGVSILE-FYLGRFPF 273
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
388-610 8.18e-12

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: 66.15  E-value: 8.18e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 388 VAIKTIREGAMSEEDFIE-------EAEVMMKLS-HPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETL 459
Cdd:cd14181  40 VKIIEVTAERLSPEQLEEvrsstlkEIHILRQVSgHPSIITLIDSYESSTFIFLVFDLMRRGELFDYLTEKVTLSEKETR 119
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 460 LGMcLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMT-RFVLDDQYTSSTGTKfpvKWASPEVFSFSR---- 534
Cdd:cd14181 120 SIM-RSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSDFGFScHLEPGEKLRELCGTP---GYLAPEILKCSMdeth 195
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 535 --YSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfrlykprlasthVYQIMNHCWKERPED-RPAFSRLLR 610
Cdd:cd14181 196 pgYGKEVDLWACGVILFTLLA-GSPPFWHRRQMLMLRMIMEG------------RYQFSSPEWDDRSSTvKDLISRLLV 261
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
364-609 8.20e-12

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: 65.87  E-value: 8.20e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYWLNK-DKVAIKTIREGAMSEEDFIE---------EAEVMMKL---SHPKLVQLYGVCLEQAP 430
Cdd:cd14004   3 TILKEMGEGAYGQVNLAIYKSKgKEVVIKFIFKERILVDTWVRdrklgtvplEIHILDTLnkrSHPNIVKLLDFFEDDEF 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEfmEHGC---LSDYLRTQRGL--FAAETLLGmclDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR 505
Cdd:cd14004  83 YYLVME--KHGSgmdLFDFIERKPNMdeKEAKYIFR---QVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAA 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 FVLDDQYTSSTGTkfpVKWASPEVFSFSRYSSKS-DVWSFGVLMWE-VFSEGkiPYenrsnSEVVEDISTGFRLYK--PR 581
Cdd:cd14004 158 YIKSGPFDTFVGT---IDYAAPEVLRGNPYGGKEqDIWALGVLLYTlVFKEN--PF-----YNIEEILEADLRIPYavSE 227
                       250       260
                ....*....|....*....|....*...
gi 15718680 582 LASTHVYQIMNHCwkerPEDRPAFSRLL 609
Cdd:cd14004 228 DLIDLISRMLNRD----VGDRPTIEELL 251
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
386-579 9.51e-12

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: 66.20  E-value: 9.51e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 386 DKVAIKTIREGAMSeedfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYL--------RTQRGLFAAE 457
Cdd:cd05630  34 EKKRIKKRKGEAMA----LNEKQILEKVNSRFVVSLAYAYETKDALCLVLTLMNGGDLKFHIyhmgqagfPEARAVFYAA 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 458 tllgmclDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQytSSTGTKFPVKWASPEVFSFSRYSS 537
Cdd:cd05630 110 -------EICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAVHVPEGQ--TIKGRVGTVGYMAPEVVKNERYTF 180
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 15718680 538 KSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDIStgfRLYK 579
Cdd:cd05630 181 SPDWWALGCLLYEMI-AGQSPFQQRKKKIKREEVE---RLVK 218
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
367-615 9.54e-12

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, 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, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The BMPR1 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: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 65.96  E-value: 9.54e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWlNKDKVAIK---TIREGAMSEEDFIEEAeVMMKlsHPKLV--------------QLYgvcleqa 429
Cdd:cd14144   1 RSVGKGRYGEVWKGKW-RGEKVAVKiffTTEEASWFRETEIYQT-VLMR--HENILgfiaadikgtgswtQLY------- 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 picLVFEFMEHGCLSDYLRTQrgLFAAETLLGMCLDVCEGMAYLE-EAC-------VIHRDLAARNCLVGENQVIKVSDF 501
Cdd:cd14144  70 ---LITDYHENGSLYDFLRGN--TLDTQSMLKLAYSAACGLAHLHtEIFgtqgkpaIAHRDIKSKNILVKKNGTCCIADL 144
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 502 GM-TRFV-----LDDQYTSSTGTKfpvKWASPEVFS-------FSRYsSKSDVWSFGVLMWEV---------FSEGKIPY 559
Cdd:cd14144 145 GLaVKFIsetneVDLPPNTRVGTK---RYMAPEVLDeslnrnhFDAY-KMADMYSFGLVLWEIarrcisggiVEEYQLPY 220
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 560 ENR-SNSEVVEDIS-----TGFRLYKPRLASTH-----VYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14144 221 YDAvPSDPSYEDMRrvvcvERRRPSIPNRWSSDevlrtMSKLMSECWAHNPAARLTALRVKKTLGKL 287
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
367-556 1.13e-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: 66.44  E-value: 1.13e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGY-WLNKDKVAIKTIRE----GAMSEEDFiEEAEVMMKLSHPKLVQLYGVCLEQAP-ICLVFEFMeh 440
Cdd:cd07856  16 QPVGMGAFGLVCSARdQLTGQNVAVKKIMKpfstPVLAKRTY-RELKLLKHLRHENIISLSDIFISPLEdIYFVTELL-- 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQRGL---FAAETLLgmclDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfVLDDQYTSSTG 517
Cdd:cd07856  93 GTDLHRLLTSRPLekqFIQYFLY----QILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLAR-IQDPQMTGYVS 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 15718680 518 TKFpvkWASPEV-FSFSRYSSKSDVWSFGVLMWEVFsEGK 556
Cdd:cd07856 168 TRY---YRAPEImLTWQKYDVEVDIWSAGCIFAEML-EGK 203
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
414-571 1.14e-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: 66.17  E-value: 1.14e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 414 SHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARNCLV--- 490
Cdd:cd14092  57 GHPNIVKLHEVFQDELHTYLVMELLRGGELLERIRKKKRFTESEASRIM-RQLVSAVSFMHSKGVVHRDLKPENLLFtde 135
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 491 GENQVIKVSDFGMTRFVLDDQytSSTGTKFPVKWASPEVFSFSR----YSSKSDVWSFGVLMWEVFSeGKIPYENRSNSE 566
Cdd:cd14092 136 DDDAEIKIVDFGFARLKPENQ--PLKTPCFTLPYAAPEVLKQALstqgYDESCDLWSLGVILYTMLS-GQVPFQSPSRNE 212

                ....*
gi 15718680 567 VVEDI 571
Cdd:cd14092 213 SAAEI 217
BTK pfam00779
BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found ...
119-148 1.28e-11

BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 459937  Cd Length: 30  Bit Score: 59.08  E-value: 1.28e-11
                          10        20        30
                  ....*....|....*....|....*....|
gi 15718680   119 KYHPNFWMDGKWRCCSQLEKLATGCAQYDP 148
Cdd:pfam00779   1 KYHPGAFVDGKWLCCKQTDKNAPGCSPVTS 30
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
401-574 1.82e-11

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: 64.94  E-value: 1.82e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 401 EDFIEEAEVMMKLS-HPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAET--LLGMCLDVCEgmaYLEEAC 477
Cdd:cd14182  54 EATLKEIDILRKVSgHPNIIQLKDTYETNTFFFLVFDLMKKGELFDYLTEKVTLSEKETrkIMRALLEVIC---ALHKLN 130
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 478 VIHRDLAARNCLVGENQVIKVSDFGMT-RFVLDDQYTSSTGTKfpvKWASPEVFSFSR------YSSKSDVWSFGVLMWE 550
Cdd:cd14182 131 IVHRDLKPENILLDDDMNIKLTDFGFScQLDPGEKLREVCGTP---GYLAPEIIECSMddnhpgYGKEVDMWSTGVIMYT 207
                       170       180
                ....*....|....*....|....
gi 15718680 551 VFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd14182 208 LLA-GSPPFWHRKQMLMLRMIMSG 230
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
369-602 1.94e-11

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: 65.75  E-value: 1.94e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAM----SEEDFIEEAEVMMK-LSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd05604   4 IGKGSFGKVLLAKRKRDGKYyAVKVLQKKVIlnrkEQKHIMAERNVLLKnVKHPFLVGLHYSFQTTDKLYFVLDFVNGGE 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGlFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPv 522
Cdd:cd05604  84 LFFHLQRERS-FPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCKEGISNSDTTTTFCGTP- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 523 KWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDIstgfrLYKPRL----ASTHVYQIMNHCWKER 598
Cdd:cd05604 162 EYLAPEVIRKQPYDNTVDWWCLGSVLYEML-YGLPPFYCRDTAEMYENI-----LHKPLVlrpgISLTAWSILEELLEKD 235

                ....
gi 15718680 599 PEDR 602
Cdd:cd05604 236 RQLR 239
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
364-609 2.20e-11

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD 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: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 65.39  E-value: 2.20e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGL--VHLGYWLNKDK-VAIKTIREGAMSEEDF--IEEAEVMMK-LSHPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd08216   1 ELLYEIGKCFKGGgvVHLAKHKPTNTlVAVKKINLESDSKEDLkfLQQEILTSRqLQHPNILPYVTSFVVDNDLYVVTPL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQ--RGLfaAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDF---------GMTR 505
Cdd:cd08216  81 MAYGSCRDLLKTHfpEGL--PELAIAFILrDVLNALEYIHSKGYIHRSVKASHILISGDGKVVLSGLryaysmvkhGKRQ 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 FVLDDQYTSSTgtkFPVKWASPEVF--SFSRYSSKSDVWSFGVLMWEV------FSE------------GKIP------- 558
Cdd:cd08216 159 RVVHDFPKSSE---KNLPWLSPEVLqqNLLGYNEKSDIYSVGITACELangvvpFSDmpatqmllekvrGTTPqlldcst 235
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 559 ---YENR---SNSEVVED--ISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd08216 236 yplEEDSmsqSEDSSTEHpnNRDTRDIPYQRTFSEAFHQFVELCLQRDPELRPSASQLL 294
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
394-564 2.34e-11

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like 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: 270913 [Multi-domain]  Cd Length: 287  Bit Score: 65.04  E-value: 2.34e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 394 REGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLE------------QAPICLVFEFME-----HGCLSDYlrtqrG 452
Cdd:cd14011  36 EYSKRDREQILEllkrGVKQLTRLRHPRILTVQHPLEEsreslafatepvFASLANVLGERDnmpspPPELQDY-----K 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 453 LFAAETLLGMcLDVCEGMAYL-EEACVIHRDLAARNCLVGENQVIKVSDFGmtrFVLDDQYTSSTGTKFPVK-------- 523
Cdd:cd14011 111 LYDVEIKYGL-LQISEALSFLhNDVKLVHGNICPESVVINSNGEWKLAGFD---FCISSEQATDQFPYFREYdpnlppla 186
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 15718680 524 -----WASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSN 564
Cdd:cd14011 187 qpnlnYLAPEYILSKTCDPASDMFSLGVLIYAIYNKGKPLFDCVNN 232
SH3_SPIN90 cd11849
Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also ...
178-226 2.65e-11

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212783 [Multi-domain]  Cd Length: 53  Bit Score: 58.87  E-value: 2.65e-11
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 178 ALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYL 226
Cdd:cd11849   4 ALYDFKSAEPNTLSFSEGETFLLLERSNAHWWLVTNHSGETGYVPANYV 52
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
367-615 2.74e-11

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, 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, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The BMPR1a 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: 271122 [Multi-domain]  Cd Length: 287  Bit Score: 64.68  E-value: 2.74e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWlNKDKVAIK---TIREGAMSEEDFIEEAeVMMKlsHPKLVQLYGVCLE----QAPICLVFEFME 439
Cdd:cd14220   1 RQIGKGRYGEVWMGKW-RGEKVAVKvffTTEEASWFRETEIYQT-VLMR--HENILGFIAADIKgtgsWTQLYLITDYHE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRglFAAETLLGMCLDVCEGMAYLE--------EACVIHRDLAARNCLVGENQVIKVSDFGM-TRF---- 506
Cdd:cd14220  77 NGSLYDFLKCTT--LDTRALLKLAYSAACGLCHLHteiygtqgKPAIAHRDLKSKNILIKKNGTCCIADLGLaVKFnsdt 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 -VLDDQYTSSTGTKfpvKWASPEVFS-------FSRYsSKSDVWSFGVLMWE---------VFSEGKIPYENR-SNSEVV 568
Cdd:cd14220 155 nEVDVPLNTRVGTK---RYMAPEVLDeslnknhFQAY-IMADIYSFGLIIWEmarrcvtggIVEEYQLPYYDMvPSDPSY 230
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 569 EDIS--TGFRLYKPRLAS--------THVYQIMNHCWKERPEDRPAFSRLLRQLAEI 615
Cdd:cd14220 231 EDMRevVCVKRLRPTVSNrwnsdeclRAVLKLMSECWAHNPASRLTALRIKKTLAKM 287
SH3_Nck2_1 cd11899
First Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
172-229 3.51e-11

First Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck2 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212832 [Multi-domain]  Cd Length: 58  Bit Score: 58.60  E-value: 3.51e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 172 EETVVIALYDYQTNDPQELALRRNEEYCLLDSSEIhWWRVQDRNGHEGYVPSSYLVEK 229
Cdd:cd11899   2 EEVIVIAKWDYTAQQDQELDIKKNERLWLLDDSKT-WWRVRNAANRTGYVPSNYVERK 58
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
365-571 3.61e-11

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: 64.11  E-value: 3.61e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd14104   4 IAEELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKkEISILNIARHRNILRLHESFESHEELVMIFEFISGVDI 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARN--CLVGENQVIKVSDFGMTRFV-----LDDQYTSSt 516
Cdd:cd14104  84 FERITTARFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENiiYCTRRGSYIKIIEFGQSRQLkpgdkFRLQYTSA- 162
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15718680 517 gtkfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14104 163 ------EFYAPEVHQHESVSTATDMWSLGCLVYVLLS-GINPFEAETNQQTIENI 210
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
369-543 4.00e-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: 64.07  E-value: 4.00e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVH------LGYWLNKDKVAIKTIRegamseedfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd13991  14 IGRGSFGEVHrmedkqTGFQCAVKKVRLEVFR---------AEELMACAGLTSPRVVPLYGAVREGPWVNIFMDLKEGGS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGEN-QVIKVSDFGMTRFVLDDQYTSS--TGTK 519
Cdd:cd13991  85 LGQLIK-EQGCLPEDRALHYLGQALEGLEYLHSRKILHGDVKADNVLLSSDgSDAFLCDFGHAECLDPDGLGKSlfTGDY 163
                       170       180
                ....*....|....*....|....*.
gi 15718680 520 FP--VKWASPEVFSFSRYSSKSDVWS 543
Cdd:cd13991 164 IPgtETHMAPEVVLGKPCDAKVDVWS 189
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
366-550 5.09e-11

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: 64.18  E-value: 5.09e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEH 440
Cdd:cd05574   6 IKLLGKGDVGRVYLVRLKGTGKLfAMKVLDKEEMIKRNKVKrvltEREILATLDHPFLPTLYASFQTSTHLCFVMDYCPG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 441 GCLSDYLRTQRG---------LFAAETLLgmcldvceGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFgmtrfvlDDQ 511
Cdd:cd05574  86 GELFRLLQKQPGkrlpeevarFYAAEVLL--------ALEYLHLLGFVYRDLKPENILLHESGHIMLTDF-------DLS 150
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 512 YTSSTGTKFPVK-----------------------------------WASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd05574 151 KQSSVTPPPVRKslrkgsrrssvksieketfvaepsarsnsfvgteeYIAPEVIKGDGHGSAVDWWTLGILLYE 224
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
406-551 5.67e-11

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 64.63  E-value: 5.67e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  406 EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGcLSDYLRTQRGLfAAETLLGMCLDVCEGMAYLEEACVIHRDLAA 485
Cdd:PHA03212 133 EAHILRAINHPSIIQLKGTFTYNKFTCLILPRYKTD-LYCYLAAKRNI-AICDILAIERSVLRAIQYLHENRIIHRDIKA 210
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680  486 RNCLVGENQVIKVSDFGMTRFVLD---DQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEV 551
Cdd:PHA03212 211 ENIFINHPGDVCLGDFGAACFPVDinaNKYYGWAGT---IATNAPELLARDPYGPAVDIWSAGIVLFEM 276
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
369-502 5.83e-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: 60.53  E-value: 5.83e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHL--GYWLNKdKVAIKTIREGAMSEEDFIE-EAEVMMKLSHPKL--VQLYGVCLEQAPICLVFEFMEHGCL 443
Cdd:cd13968   1 MGEGASAKVFWaeGECTTI-GVAVKIGDDVNNEEGEDLEsEMDILRRLKGLELniPKVLVTEDVDGPNILLMELVKGGTL 79
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 444 SDYLrTQRGLFAAETLlGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG 502
Cdd:cd13968  80 IAYT-QEEELDEKDVE-SIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
363-606 6.81e-11

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: 62.92  E-value: 6.81e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 363 LTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIRE-GAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEF---- 437
Cdd:cd14111   5 YTFLDEKARGRFGVIRRCRENATGKNFPAKIVPyQAEEKQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEFcsgk 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 -MEHGcLSDYLRtqrglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR----FVLdDQY 512
Cdd:cd14111  85 eLLHS-LIDRFR-----YSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQsfnpLSL-RQL 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 513 TSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG----FRLYkPRL---AST 585
Cdd:cd14111 158 GRRTGT---LEYMAPEMVKGEPVGPPADIWSIGVLTYIMLS-GRSPFEDQDPQETEAKILVAkfdaFKLY-PNVsqsASL 232
                       250       260
                ....*....|....*....|..
gi 15718680 586 HVYQIMN-HCWKeRPEDRPAFS 606
Cdd:cd14111 233 FLKKVLSsYPWS-RPTTKDCFA 253
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
365-571 7.50e-11

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: 63.53  E-value: 7.50e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMS-EEDFIE-EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd14168  14 FKEVLGTGAFSEVVLAEERATGKLfAVKCIPKKALKgKESSIEnEIAVLRKIKHENIVALEDIYESPNHLYLVMQLVSGG 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 CLSDYLrTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV---GENQVIKVSDFGMTRFV-LDDQYTSSTG 517
Cdd:cd14168  94 ELFDRI-VEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLYfsqDEESKIMISDFGLSKMEgKGDVMSTACG 172
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 15718680 518 TKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd14168 173 TP---GYVAPEVLAQKPYSKAVDCWSIGVIAYILLC-GYPPFYDENDSKLFEQI 222
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
367-609 8.99e-11

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: 62.60  E-value: 8.99e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLV----HLGywlNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd14107   8 EEIGRGTFGFVkrvtHKG---NGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELCSSEE 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGLFAAETLLGMcLDVCEGMAYLEEACVIHRDLAARNCLV--GENQVIKVSDFGMTRFV--LDDQYTSSTGT 518
Cdd:cd14107  85 LLDRLFLKGVVTEAEVKLYI-QQVLEGIGYLHGMNILHLDIKPDNILMvsPTREDIKICDFGFAQEItpSEHQFSKYGSP 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 519 KFpvkwASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGfRLY--KPRLA--STHVYQIMNHC 594
Cdd:cd14107 164 EF----VAPEIVHQEPVSAATDIWALGVIAYLSLT-CHSPFAGENDRATLLNVAEG-VVSwdTPEIThlSEDAKDFIKRV 237
                       250
                ....*....|....*
gi 15718680 595 WKERPEDRPAFSRLL 609
Cdd:cd14107 238 LQPDPEKRPSASECL 252
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
366-615 9.07e-11

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: 62.67  E-value: 9.07e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIregaMSEEDF----IEEAEVMMKLS------HPKLVQLYGVCLEQAPICLV 434
Cdd:cd14133   4 LEVLGKGTFGQVVKCYDLLTGEeVALKII----KNNKDYldqsLDEIRLLELLNkkdkadKYHIVRLKDVFYFKNHLCIV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGcLSDYLRTQRglfaaETLLGMCL------DVCEGMAYLEEACVIHRDLAARNCLVGENQ--VIKVSDFGMTRF 506
Cdd:cd14133  80 FELLSQN-LYEFLKQNK-----FQYLSLPRirkiaqQILEALVFLHSLGLIHCDLKPENILLASYSrcQIKIIDFGSSCF 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 507 VLDDQYT---SSTgtkfpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRLYKPRLA 583
Cdd:cd14133 154 LTQRLYSyiqSRY-------YRAPEVILGLPYDEKIDMWSLGCILAELYT-GEPLFPGASEVDQLARIIGTIGIPPAHML 225
                       250       260       270
                ....*....|....*....|....*....|..
gi 15718680 584 SthvyqimnhcwkERPEDRPAFSRLLRQLAEI 615
Cdd:cd14133 226 D------------QGKADDELFVDFLKKLLEI 245
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
365-574 9.40e-11

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: 62.63  E-value: 9.40e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 365 FVQEIGSGQFGLVHLGywlnKDKV-----AIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLeqAPICLVFefME 439
Cdd:cd14110   7 FQTEINRGRFSVVRQC----EEKRsgqmlAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYL--SPRHLVL--IE 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLR---TQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSST 516
Cdd:cd14110  79 ELCSGPELLynlAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKVLMTD 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 517 GTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTG 574
Cdd:cd14110 159 KKGDYVETMAPELLEGQGAGPQTDIWAIGVTAFIMLS-ADYPVSSDLNWERDRNIRKG 215
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
367-572 9.94e-11

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: 62.63  E-value: 9.94e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHLGYWLNKDKVA----IKTIREGAMSEEDFIEEAEVM-MKLSHPKLVQLYGVCLEQAPICLVFEFMEHG 441
Cdd:cd14198  14 KELGRGKFAVVRQCISKSTGQEYaakfLKKRRRGQDCRAEILHEIAVLeLAKSNPRVVNLHEVYETTSEIILILEYAAGG 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 442 -----CLSDylrtQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCL------VGEnqvIKVSDFGMTRFVLDD 510
Cdd:cd14198  94 eifnlCVPD----LAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILlssiypLGD---IKIVDFGMSRKIGHA 166
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 511 -QYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDIS 572
Cdd:cd14198 167 cELREIMGTP---EYLAPEILNYDPITTATDMWNIGVIAYMLLT-HESPFVGEDNQETFLNIS 225
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
361-609 1.00e-10

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: 62.91  E-value: 1.00e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 361 SELTFVQEIGSGQFGLVH-LGYWLNKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLE--------Q 428
Cdd:cd14049   6 NEFEEIARLGKGGYGKVYkVRNKLDGQYYAIKKILIKKVTKRDcmkVLREVKVLAGLQHPNIVGYHTAWMEhvqlmlyiQ 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 429 APIC------LVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLV-GENQVIKVSDF 501
Cdd:cd14049  86 MQLCelslwdWIVERNKRPCEEEFKSAPYTPVDVDVTTKILQQLLEGVTYIHSMGIVHRDLKPRNIFLhGSDIHVRIGDF 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 502 GMT----------RFVLDDQYTSSTGTKF-PVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFsegkIPYENR-SNSEVVE 569
Cdd:cd14049 166 GLAcpdilqdgndSTTMSRLNGLTHTSGVgTCLYAAPEQLEGSHYDFKSDMYSIGVILLELF----QPFGTEmERAEVLT 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 15718680 570 DISTG-----FRLYKPRLAsthvyQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd14049 242 QLRNGqipksLCKRWPVQA-----KYIKLLTSTEPSERPSASQLL 281
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
389-611 1.05e-10

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: 62.64  E-value: 1.05e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 389 AIKTIREGAMSE----EDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMcL 464
Cdd:cd14189  30 AVKVIPHSRVAKphqrEKIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKSLAHIWKARHTLLEPEVRYYL-K 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 465 DVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPvKWASPEVFSFSRYSSKSDVWSF 544
Cdd:cd14189 109 QIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPEQRKKTICGTP-NYLAPEVLLRQGHGPESDVWSL 187
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 545 GVLMWEVFSeGKIPYEnrsnsevVEDISTGFRLYK------PRLASTHVYQIMNHCWKERPEDRPAFSRLLRQ 611
Cdd:cd14189 188 GCVMYTLLC-GNPPFE-------TLDLKETYRCIKqvkytlPASLSLPARHLLAGILKRNPGDRLTLDQILEH 252
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
239-333 1.06e-10

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. 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: 198207  Cd Length: 104  Bit Score: 58.66  E-value: 1.06e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 239 WYNKSISRDKAEKLLLDTG-KEGAFMVRDSRT-AGTYTVSVftKAVVSENNPCIKHYHIKETNDNpkRYYVAEKYVFDSI 316
Cdd:cd10344  12 WLFEGLSREKAEELLMLPGnQVGSFLIRESETrRGCYSLSV--RHRGSQSRDSVKHYRIFRLDNG--WFYISPRLTFQCL 87
                        90
                ....*....|....*..
gi 15718680 317 PLLINYHQHNGGGLVTR 333
Cdd:cd10344  88 EDMVNHYSESADGLCCV 104
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
235-337 1.24e-10

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: 58.29  E-value: 1.24e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 235 ETYEWYNKSISRDKAEKLLLDTGKE-GAFMVRDSRT-AGTYTVSVftkavvsENNPCIKHYHIKETNDNPkrYYVAEKYV 312
Cdd:cd10370   1 EAEPWYFGKIKRIEAEKKLLLPENEhGAFLIRDSESrHNDYSLSV-------RDGDTVKHYRIRQLDEGG--FFIARRTT 71
                        90       100
                ....*....|....*....|....*
gi 15718680 313 FDSIPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd10370  72 FRTLQELVEHYSKDSDGLCVNLRKP 96
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
360-553 1.30e-10

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: 63.09  E-value: 1.30e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 360 PSELTFVQEIGSGQFGLVHLGY-WLNKDKVAIKTIR--EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVcleQAP------ 430
Cdd:cd07849   4 GPRYQNLSYIGEGAYGMVCSAVhKPTGQKVAIKKISpfEHQTYCLRTLREIKILLRFKHENIIGILDI---QRPptfesf 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 --ICLVFEFMEHGcLSDYLRTQR------GLFAAETLlgmcldvcEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFG 502
Cdd:cd07849  81 kdVYIVQELMETD-LYKLIKTQHlsndhiQYFLYQIL--------RGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFG 151
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 503 MTRfvLDDQYTSSTG--TKF-PVKW-ASPEV-FSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:cd07849 152 LAR--IADPEHDHTGflTEYvATRWyRAPEImLNSKGYTKAIDIWSVGCILAEMLS 205
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
390-572 1.38e-10

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: 62.37  E-value: 1.38e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 390 IKTIREGAMSEEDFIEEAEV-MMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMcLDVCE 468
Cdd:cd14106  41 LRKRRRGQDCRNEILHEIAVlELCKDCPRVVNLHEVYETRSELILILELAAGGELQTLLDEEECLTEADVRRLM-RQILE 119
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 469 GMAYLEEACVIHRDLAARNCLVGENQV---IKVSDFGMTRFVlddqytsSTGTKF-----PVKWASPEVFSFSRYSSKSD 540
Cdd:cd14106 120 GVQYLHERNIVHLDLKPQNILLTSEFPlgdIKLCDFGISRVI-------GEGEEIreilgTPDYVAPEILSYEPISLATD 192
                       170       180       190
                ....*....|....*....|....*....|..
gi 15718680 541 VWSFGVLMWeVFSEGKIPYENRSNSEVVEDIS 572
Cdd:cd14106 193 MWSIGVLTY-VLLTGHSPFGGDDKQETFLNIS 223
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
362-509 1.47e-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: 62.97  E-value: 1.47e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 362 ELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIEEAEV---MMKLSH-PKLVQLYGVCLEQAPICLVFE 436
Cdd:cd05610   5 EFVIVKPISRGAFGKVYLGRKKNNSKLyAVKVVKKADMINKNMVHQVQAerdALALSKsPFIVHLYYSLQSANNVYLVME 84
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 437 FMEHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD 509
Cdd:cd05610  85 YLIGGDVKSLLHIY-GYFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVTLN 156
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
366-550 1.55e-10

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: 62.87  E-value: 1.55e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLVHLGYWLNKDK-VAIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVC--------------LEQA 429
Cdd:cd07854  10 LRPLGCGSNGLVFSAVDSDCDKrVAVKKIVlTDPQSVKHALREIKIIRRLDHDNIVKVYEVLgpsgsdltedvgslTELN 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFM--------EHGCLS-DYLRtqrgLFAAETLlgmcldvcEGMAYLEEACVIHRDLAARNCLVG-ENQVIKVS 499
Cdd:cd07854  90 SVYIVQEYMetdlanvlEQGPLSeEHAR----LFMYQLL--------RGLKYIHSANVLHRDLKPANVFINtEDLVLKIG 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 500 DFGMTRfVLDDQYTS----STGTKfpVKW-ASPE-VFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd07854 158 DFGLAR-IVDPHYSHkgylSEGLV--TKWyRSPRlLLSPNNYTKAIDMWAAGCIFAE 211
STKc_aPKC cd05588
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the ...
369-566 2.04e-10

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: 62.44  E-value: 2.04e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLS-HPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd05588   3 IGRGSYAKVLMVELKKTKRIyAMKVIKKELVNDDEDIDwvqtEKHVFETASnHPFLVGLHSCFQTESRLFFVIEFVNGGD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQRGL-------FAAEtllgmcldVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd05588  83 LMFHMQRQRRLpeeharfYSAE--------ISLALNFLHEKGIIYRDLKLDNVLLDSEGHIKLTDYGMCKEGLRPGDTTS 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 516 TGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSE 566
Cdd:cd05588 155 TFCGTP-NYIAPEILRGEDYGFSVDWWALGVLMFEMLA-GRSPFDIVGSSD 203
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
369-550 2.20e-10

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: 62.25  E-value: 2.20e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVhlgyWLNKDK-----VAIKTIREGAMSEEDFIE----EAEVMMKLSHPKLVQLYgvCLEQAPICL--VFEF 437
Cdd:cd05599   9 IGRGAFGEV----RLVRKKdtghvYAMKKLRKSEMLEKEQVAhvraERDILAEADNPWVVKLY--YSFQDEENLylIMEF 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCL------SDYL---RTQrgLFAAETLLGmcLDVCEGMAYleeacvIHRDLAARNCLVGENQVIKVSDFGMTRFVL 508
Cdd:cd05599  83 LPGGDMmtllmkKDTLteeETR--FYIAETVLA--IESIHKLGY------IHRDIKPDNLLLDARGHIKLSDFGLCTGLK 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 15718680 509 DDQYTSST-GTkfPvKWASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd05599 153 KSHLAYSTvGT--P-DYIAPEVFLQKGYGKECDWWSLGVIMYE 192
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
369-571 2.20e-10

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: 62.41  E-value: 2.20e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAMSEEDFIE----EAEVMMKLSHPK-LVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd05587   4 LGKGSFGKVMLAERKGTDELyAIKILKKDVIIQDDDVEctmvEKRVLALSGKPPfLTQLHSCFQTMDRLYFVMEYVNGGD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSdYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPv 522
Cdd:cd05587  84 LM-YHIQQVGKFKEPVAVFYAAEIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKEGIFGGKTTRTFCGTP- 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 523 KWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDI 571
Cdd:cd05587 162 DYIAPEIIAYQPYGKSVDWWAYGVLLYEMLA-GQPPFDGEDEDELFQSI 209
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
360-557 2.29e-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: 62.37  E-value: 2.29e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 360 PSELTFVQEIGSGQFGLVHLGYWLN-KDKVAIKTIR---EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPI---- 431
Cdd:cd07878  14 PERYQNLTPVGSGAYGSVCSAYDTRlRQKVAVKKLSrpfQSLIHARRTYRELRLLKHMKHENVIGLLDVFTPATSIenfn 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 --CLVFEFMEHGcLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVlD 509
Cdd:cd07878  94 evYLVTNLMGAD-LNNIVKCQK--LSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQA-D 169
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 15718680 510 DQYTSSTGTKFpvkWASPEV-FSFSRYSSKSDVWSFGVLMWEVFsEGKI 557
Cdd:cd07878 170 DEMTGYVATRW---YRAPEImLNWMHYNQTVDIWSVGCIMAELL-KGKA 214
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
478-609 2.43e-10

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 63.35  E-value: 2.43e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  478 VIHRDLAARNCLVGENQVIKVSDFGMTRF----VLDDQYTSSTGTKFPVkwaSPEVFSFSRYSSKSDVWSFGVLMWEVFS 553
Cdd:PTZ00283 164 MIHRDIKSANILLCSNGLVKLGDFGFSKMyaatVSDDVGRTFCGTPYYV---APEIWRRKPYSKKADMFSLGVLLYELLT 240
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680  554 EgKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:PTZ00283 241 L-KRPFDGENMEEVMHKTLAGRYDPLPPSISPEMQEIVTALLSSDPKRRPSSSKLL 295
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
366-584 2.49e-10

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: 61.67  E-value: 2.49e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 366 VQEIGSGQFGLV-HLGYWLNKDKV-AIKTIRE---GAMSEEDFIEEAEVMMKLS---HPKLVQLYGVCLEQAPICLVFEF 437
Cdd:cd14052   5 VELIGSGEFSQVyKVSERVPTGKVyAVKKLKPnyaGAKDRLRRLEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQTEL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 438 MEHGCLSDYLRTQrGLFAA---ETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTS 514
Cdd:cd14052  85 CENGSLDVFLSEL-GLLGRldeFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVWPLIRGIE 163
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15718680 515 STGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWE-----VFSEGKIPYEN-RSNsevveDISTGFRLYKPRLAS 584
Cdd:cd14052 164 REGDR---EYIAPEILSEHMYDKPADIFSLGLILLEaaanvVLPDNGDAWQKlRSG-----DLSDAPRLSSTDLHS 231
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
369-580 2.50e-10

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: 62.29  E-value: 2.50e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDKV-AIKTIREGAM----SEEDFIEEAEVMMK-LSHPKLVQLYGVCLEQAPICLVFEFMEHGC 442
Cdd:cd05603   3 IGKGSFGKVLLAKRKCDGKFyAVKVLQKKTIlkkkEQNHIMAERNVLLKnLKHPFLVGLHYSFQTSEKLYFVLDYVNGGE 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 443 LSDYLRTQR-------GLFAAEtllgmcldVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSS 515
Cdd:cd05603  83 LFFHLQRERcflepraRFYAAE--------VASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCKEGMEPEETTS 154
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15718680 516 TGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYENRSNSEVVEDIstgfrLYKP 580
Cdd:cd05603 155 TFCGTP-EYLAPEVLRKEPYDRTVDWWCLGAVLYEML-YGLPPFYSRDVSQMYDNI-----LHKP 212
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
359-558 2.58e-10

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: 61.93  E-value: 2.58e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 359 DPSEL-TFVQEIGSGQFGLVH-LGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLS-HPKLVQLYGVCLEQ-----AP 430
Cdd:cd06639  19 DPSDTwDIIETIGKGTYGKVYkVTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLPnHPNVVKFYGMFYKAdqyvgGQ 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 431 ICLVFEFMEHGCLSDYLRT--QRGLFAAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfv 507
Cdd:cd06639  99 LWLVLELCNGGSVTELVKGllKCGQRLDEAMISYILyGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSA-- 176
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15718680 508 lddQYTS-------STGTKFpvkWASPEVFSFSR-----YSSKSDVWSFGVLMWEVfSEGKIP 558
Cdd:cd06639 177 ---QLTSarlrrntSVGTPF---WMAPEVIACEQqydysYDARCDVWSLGITAIEL-ADGDPP 232
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
369-556 2.67e-10

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: 61.55  E-value: 2.67e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLV-HLGYWLNKDKVAIKTIREGAMSEE---DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLs 444
Cdd:cd07848   9 VGEGAYGVVlKCRHKETKEIVAIKKFKDSEENEEvkeTTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNML- 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 445 DYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFV---LDDQYTSSTGTKFp 521
Cdd:cd07848  88 ELLEEMPNGVPPEKVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLsegSNANYTEYVATRW- 166
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15718680 522 vkWASPEVFSFSRYSSKSDVWSFGVLMWEVfSEGK 556
Cdd:cd07848 167 --YRSPELLLGAPYGKAVDMWSVGCILGEL-SDGQ 198
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
364-612 2.93e-10

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 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: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 61.54  E-value: 2.93e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 364 TFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIR-EGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCL-EQAP----ICLVFE 436
Cdd:cd13986   3 RIQRLLGEGGFSFVYLVEDLSTGRLyALKKILcHSKEDVKEAMREIENYRLFNHPNILRLLDSQIvKEAGgkkeVYLLLP 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGCLSDYLRTQR--GLFAAET-LLGMCLDVCEGMAYLEEAC---VIHRDLAARNCLVGENQVIKVSDFG-MTRFVLd 509
Cdd:cd13986  83 YYKRGSLQDEIERRLvkGTFFPEDrILHIFLGICRGLKAMHEPElvpYAHRDIKPGNVLLSEDDEPILMDLGsMNPARI- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 510 dQYTSSTGTKFPVKWAS---------PEVF---SFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDISTGFRL 577
Cdd:cd13986 162 -EIEGRREALALQDWAAehctmpyraPELFdvkSHCTIDEKTDIWSLGCTLYALMY-GESPFERIFQKGDSLALAVLSGN 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 15718680 578 YKPrlASTHVY-----QIMNHCWKERPEDRPAFSRLLRQL 612
Cdd:cd13986 240 YSF--PDNSRYseelhQLVKSMLVVNPAERPSIDDLLSRV 277
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
238-334 3.28e-10

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: 57.37  E-value: 3.28e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 238 EWYNKSISRDKAEKLLLD-TGKEGAFMVRDSRTA-GTYTVSVFTKAVVSENNpcIKHYHIKETNDNPkrYYVAEKYVFDS 315
Cdd:cd10365   4 EWYFGKITRRESERLLLNaENPRGTFLVRESETTkGAYCLSVSDFDNAKGLN--VKHYKIRKLDSGG--FYITSRTQFNS 79
                        90
                ....*....|....*....
gi 15718680 316 IPLLINYHQHNGGGLVTRL 334
Cdd:cd10365  80 LQQLVAYYSKHADGLCHRL 98
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
238-337 3.60e-10

N-terminal Src homology 2 (N-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: 199829  Cd Length: 99  Bit Score: 56.98  E-value: 3.60e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 238 EWYNKSIS--RDKAEKLLLD--TGKEGAFMVRDSRT-AGTYTVSVFTKAVVsennpciKHYHIKETNDN-PKRYYVAEKY 311
Cdd:cd10341   5 PWFHGKLGdgRDEAEKLLLEycEGGDGTFLVRESETfVGDYTLSFWRNGKV-------QHCRIRSRQENgEKKYYLTDNL 77
                        90       100
                ....*....|....*....|....*.
gi 15718680 312 VFDSIPLLINYHQHNggglvtRLRYP 337
Cdd:cd10341  78 VFDSLYELIDYYRQN------PLRCA 97
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
7-106 3.74e-10

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 56.78  E-value: 3.74e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   7 LEEQLIKKSQQKRRtspsNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRIKCVEIVKSDISipchyKYPFQVVHDN 86
Cdd:cd00821   1 KEGYLLKRGGGGLK----SWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKER-----PHCFELVTPD 71
                        90       100
                ....*....|....*....|.
gi 15718680  87 YLLYVF-APDRESRQRWVLAL 106
Cdd:cd00821  72 GRTYYLqADSEEERQEWLKAL 92
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
361-599 4.32e-10

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 62.83  E-value: 4.32e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   361 SELTFVQEIGSGQFGLVHL-GYWLNKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQA--PICLV 434
Cdd:PTZ00266   13 NEYEVIKKIGNGRFGEVFLvKHKRTQEFFCWKAISYRGLKEREksqLVIEVNVMRELKHKNIVRYIDRFLNKAnqKLYIL 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   435 FEFMEHGCLSDYLRTQRGLFAA---ETLLGMCLDVCEGMAYLEE-------ACVIHRDLAARNCLVGEN----------- 493
Cdd:PTZ00266   93 MEFCDAGDLSRNIQKCYKMFGKieeHAIVDITRQLLHALAYCHNlkdgpngERVLHRDLKPQNIFLSTGirhigkitaqa 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   494 ------QVIKVSDFGMTRFV-LDDQYTSSTGTkfPVKWaSPEVF--SFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSN 564
Cdd:PTZ00266  173 nnlngrPIAKIGDFGLSKNIgIESMAHSCVGT--PYYW-SPELLlhETKSYDDKSDMWALGCIIYELCS-GKTPFHKANN 248
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 15718680   565 -SEVVEDISTGFRLY---KPRLASTHVYQIMNHCWKERP 599
Cdd:PTZ00266  249 fSQLISELKRGPDLPikgKSKELNILIKNLLNLSAKERP 287
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
367-572 4.51e-10

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: 60.72  E-value: 4.51e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 367 QEIGSGQFGLVHlgYWLNKD---KVAIKTIRE---GAMSEEDFIEEAEVM-MKLSHPKLVQLYGVCLEQAPICLVFEFME 439
Cdd:cd14197  15 RELGRGKFAVVR--KCVEKDsgkEFAAKFMRKrrkGQDCRMEIIHEIAVLeLAQANPWVINLHEVYETASEMILVLEYAA 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 440 HGCLSDYLRTQRG-LFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQV---IKVSDFGMTRFVLD-DQYTS 514
Cdd:cd14197  93 GGEIFNQCVADREeAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTSESPlgdIKIVDFGLSRILKNsEELRE 172
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 515 STGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWeVFSEGKIPYENRSNSEVVEDIS 572
Cdd:cd14197 173 IMGTP---EYVAPEILSYEPISTATDMWSIGVLAY-VMLTGISPFLGDDKQETFLNIS 226
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
369-553 4.76e-10

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share 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 association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-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: 270835 [Multi-domain]  Cd Length: 286  Bit Score: 60.86  E-value: 4.76e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYW-LNKDKVAIKTIR----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMeHGCL 443
Cdd:cd07844   8 LGEGSYATVYKGRSkLTGQLVALKEIRleheEGAPFTA--IREASLLKDLKHANIVTLHDIIHTKKTLTLVFEYL-DTDL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 444 SDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRF--VLDDQYTSSTGTKFp 521
Cdd:cd07844  85 KQYMDDCGGGLSMHNVRLFLFQLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLARAksVPSKTYSNEVVTLW- 163
                       170       180       190
                ....*....|....*....|....*....|...
gi 15718680 522 vkWASPEVFSFSR-YSSKSDVWSFGVLMWEVFS 553
Cdd:cd07844 164 --YRPPDVLLGSTeYSTSLDMWGVGCIFYEMAT 194
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
356-550 4.90e-10

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: 61.54  E-value: 4.90e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 356 WVIdPSELTFVQEIGSGQFGLVHLGY-WLNKDKVAIKTIREGAMSEED---FIEEAEVMMKLSHPKLVQLYGVCLEQAPI 431
Cdd:cd07851  11 WEV-PDRYQNLSPVGSGAYGQVCSAFdTKTGRKVAIKKLSRPFQSAIHakrTYRELRLLKHMKHENVIGLLDVFTPASSL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 432 ------CLVFEFMEHGcLSDYLRTQRglFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTR 505
Cdd:cd07851  90 edfqdvYLVTHLMGAD-LNNIVKCQK--LSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLAR 166
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 15718680 506 fVLDDQYTSSTGTKFpvkWASPEV-FSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd07851 167 -HTDDEMTGYVATRW---YRAPEImLNWMHYNQTVDIWSVGCIMAE 208
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
366-554 5.17e-10

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 60.99  E-value: 5.17e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  366 VQEIGSGQFGLVHLGywlnKDK-----VAIKTIR-----EGAMSEEdfIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 435
Cdd:PLN00009   7 VEKIGEGTYGVVYKA----RDRvtnetIALKKIRleqedEGVPSTA--IREISLLKEMQHGNIVRLQDVVHSEKRLYLVF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  436 EFMEHGcLSDYLRTQRGLFAAETLLGMCL-DVCEGMAYLEEACVIHRDLAARNCLVG-ENQVIKVSDFGMTRF--VLDDQ 511
Cdd:PLN00009  81 EYLDLD-LKKHMDSSPDFAKNPRLIKTYLyQILRGIAYCHSHRVLHRDLKPQNLLIDrRTNALKLADFGLARAfgIPVRT 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 15718680  512 YTSSTGTKFpvkWASPEVFSFSR-YSSKSDVWSFGVLMWEVFSE 554
Cdd:PLN00009 160 FTHEVVTLW---YRAPEILLGSRhYSTPVDIWSVGCIFAEMVNQ 200
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
239-338 5.93e-10

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: 56.52  E-value: 5.93e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 239 WYNKSISRDKAEKLLLDTGKEGAFMVRDSRTA-GTYTVSVFTkavvseNNPCIKHYHIKETNDnpkRYYVAEKYVFDSIP 317
Cdd:cd09931   2 WFHGHLSGKEAEKLLLEKGKPGSFLVRESQSKpGDFVLSVRT------DDDKVTHIMIRCQGG---KYDVGGGEEFDSLT 72
                        90       100
                ....*....|....*....|....*
gi 15718680 318 LLINYHQHNG----GGLVTRLRYPV 338
Cdd:cd09931  73 DLVEHYKKNPmvetSGTVVHLKQPL 97
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
369-574 6.75e-10

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: 60.50  E-value: 6.75e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHL-------GYW----LNKDK-VAIKTIregamseEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFE 436
Cdd:cd14209   9 LGTGSFGRVMLvrhketgNYYamkiLDKQKvVKLKQV-------EHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVME 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 437 FMEHGCLSDYLRTQRGL-------FAAETLLGMcldvcegmAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLD 509
Cdd:cd14209  82 YVPGGEMFSHLRRIGRFsepharfYAAQIVLAF--------EYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAKRVKG 153
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15718680 510 DQYTsSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWEvFSEGKIPYENRSNSEVVEDISTG 574
Cdd:cd14209 154 RTWT-LCGTP---EYLAPEIILSKGYNKAVDWWALGVLIYE-MAAGYPPFFADQPIQIYEKIVSG 213
SH3_Nck1_1 cd11900
First Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
172-230 7.22e-10

First Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck1 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212833 [Multi-domain]  Cd Length: 59  Bit Score: 55.11  E-value: 7.22e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15718680 172 EETVVIALYDYQTNDPQELALRRNEEYCLLDSSEiHWWRVQDRNGHEGYVPSSYLVEKS 230
Cdd:cd11900   1 EEVVVVAKFDYVAQQDQELDIKKNERLWLLDDSK-SWWRVRNAMNKTGFVPSNYVERKN 58
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
387-609 7.30e-10

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: 59.95  E-value: 7.30e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 387 KVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMcLDV 466
Cdd:cd14187  38 KIVPKSLLLKPHQKEKMSMEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCRRRSLLELHKRRKALTEPEARYYL-RQI 116
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 467 CEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPvKWASPEVFSFSRYSSKSDVWSFGV 546
Cdd:cd14187 117 ILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVEYDGERKKTLCGTP-NYIAPEVLSKKGHSFEVDIWSIGC 195
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15718680 547 LMWEVFSeGKIPYENRSNSEvvedisTGFRLYK-----PRLASTHVYQIMNHCWKERPEDRPAFSRLL 609
Cdd:cd14187 196 IMYTLLV-GKPPFETSCLKE------TYLRIKKneysiPKHINPVAASLIQKMLQTDPTARPTINELL 256
STKc_SRPK cd14136
Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze ...
346-550 7.77e-10

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK 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: 271038 [Multi-domain]  Cd Length: 320  Bit Score: 60.67  E-value: 7.77e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 346 PVTAGLRY-GKWVIdpseltfVQEIGSGQFGLVHLGYWLNKDK-VAIKTIRegamSEEDFIEEAEVMMKL---------S 414
Cdd:cd14136   1 PVKIGEVYnGRYHV-------VRKLGWGHFSTVWLCWDLQNKRfVALKVVK----SAQHYTEAALDEIKLlkcvreadpK 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 415 HP---KLVQLYGVCLEQAP----ICLVFEFMEHGCL-----SDYlrtqRGLfAAETLLGMCLDVCEGMAYLEEAC-VIHR 481
Cdd:cd14136  70 DPgreHVVQLLDDFKHTGPngthVCMVFEVLGPNLLklikrYNY----RGI-PLPLVKKIARQVLQGLDYLHTKCgIIHT 144
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 482 DLAARNCLVGENQV-IKVSDFGMTRFVlDDQYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd14136 145 DIKPENVLLCISKIeVKIADLGNACWT-DKHFTEDIQTR---QYRSPEVILGAGYGTPADIWSTACMAFE 210
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
8-118 7.88e-10

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269950  Cd Length: 107  Bit Score: 56.53  E-value: 7.88e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680   8 EEQLIKKSQQKR-RTSPSNFKVRFFVLTKASLAYFEDRHGKKRTlkgSIELSRIKCVEIVKSDisiPCHYKYPFQVVHDN 86
Cdd:cd01244   2 EGYLIKRAQGRKkKFGRKNFKKRYFRLTNEALSYSKSKGKQPLC---SIPLEDILAVERVEEE---SFKMKNMFQIVQPD 75
                        90       100       110
                ....*....|....*....|....*....|..
gi 15718680  87 YLLYVFAPDRESRQRWVLALKEETRNNNSLVP 118
Cdd:cd01244  76 RTLYLQAKNVVELNEWLSALRKVCLCNPNRLP 107
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
469-563 9.06e-10

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: 60.91  E-value: 9.06e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 469 GMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRfvLDDQYTSSTGTKFPVK--WASPEVFSFSR-YSSKSDVWSFG 545
Cdd:cd07853 115 GLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLAR--VEEPDESKHMTQEVVTqyYRAPEILMGSRhYTSAVDIWSVG 192
                        90
                ....*....|....*...
gi 15718680 546 VLMWEVFSeGKIPYENRS 563
Cdd:cd07853 193 CIFAELLG-RRILFQAQS 209
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
369-613 9.15e-10

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. 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 MAP3K8 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: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 59.64  E-value: 9.15e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWL-NKDKVAIKTIREGAMSEEDfieeAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYL 447
Cdd:cd13995  12 IPRGAFGKVYLAQDTkTKKRMACKLIPVEQFKPSD----VEIQACFRHENIAELYGALLWEETVHLFMEAGEGGSVLEKL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 448 RTQRGLFAAEtLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVsDFGMTRFVLDDQYTSST--GTKFpvkWA 525
Cdd:cd13995  88 ESCGPMREFE-IIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFMSTKAVLV-DFGLSVQMTEDVYVPKDlrGTEI---YM 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 526 SPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENR--------------SNSEVVEDIstgfrlykPRLASTHVYQIM 591
Cdd:cd13995 163 SPEVILCRGHNTKADIYSLGATIIHMQT-GSPPWVRRyprsaypsylyiihKQAPPLEDI--------AQDCSPAMRELL 233
                       250       260
                ....*....|....*....|..
gi 15718680 592 NHCWKERPEDRPAFSRLLRQLA 613
Cdd:cd13995 234 EAALERNPNHRSSAAELLKHEA 255
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 ...
238-337 9.43e-10

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: 56.16  E-value: 9.43e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 238 EWYNKSISRDKAEKLLLDTGK-EGAFMVRDSRTA-GTYTVSVftKAVVSENNPCIKHYHIKETNDNPkrYYVAEKYVFDS 315
Cdd:cd10418   4 EWYFGKLGRKDAERQLLSFGNpRGTFLIRESETTkGAYSLSI--RDWDDMKGDHVKHYKIRKLDNGG--YYITTRAQFET 79
                        90       100
                ....*....|....*....|..
gi 15718680 316 IPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd10418  80 LQQLVQHYSERAAGLCCRLVVP 101
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
235-337 9.63e-10

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: 56.08  E-value: 9.63e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 235 ETYEWYNKSISRDKAEKLLLDTGK-EGAFMVRDSRTAGTYTVSVFTKAVVsennpcikhYHIKETNDNPKRYYVAEKYVF 313
Cdd:cd10402   8 ERMPWYHGSIARDEAERRLYSGAQpDGKFLLRERKESGTYALSLVYGKTV---------YHYRIDQDKSGKYSIPEGTKF 78
                        90       100
                ....*....|....*....|....
gi 15718680 314 DSIPLLINYHQHNGGGLVTRLRYP 337
Cdd:cd10402  79 DTLWQLVEYLKLKPDGLIFVLRES 102
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
231-338 1.06e-09

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 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: 198195  Cd Length: 110  Bit Score: 56.18  E-value: 1.06e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 231 PNNLETYEWYNKSISRDKAEKLLLDTgKEGAFMVRDSRTA-GTYTVSVFTkavvSENNPCIKHYHIKEtndnpkRYYVAE 309
Cdd:cd09942   1 PHSLQEAEWYWGDISREEVNEKMRDT-PDGTFLVRDASTMkGDYTLTLRK----GGNNKLIKIFHRDG------KYGFSD 69
                        90       100       110
                ....*....|....*....|....*....|....
gi 15718680 310 KYVFDSIPLLINYHQHNG-----GGLVTRLRYPV 338
Cdd:cd09942  70 PLTFNSVVELINYYRNNSlaeynRKLDVKLLYPV 103
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
239-338 1.13e-09

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: 55.76  E-value: 1.13e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 239 WYNKSISRDKAEKLLLDTgKEGAFMVRDS-RTAGTYTVSV-FTKAVvsennpciKHYHIKETNDnpkRYYVAEKYVFDSI 316
Cdd:cd09937   5 WFHGKISREEAERLLQPP-EDGLFLVREStNYPGDYTLCVsFEGKV--------EHYRVIYRNG---KLTIDEEEYFENL 72
                        90       100
                ....*....|....*....|..
gi 15718680 317 PLLINYHQHNGGGLVTRLRYPV 338
Cdd:cd09937  73 IQLVEHYTKDADGLCTRLVKPK 94
SH2_SAP1a cd10400
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked ...
240-338 1.17e-09

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: 56.01  E-value: 1.17e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 240 YNKSISRDKAEKLLLDTGKEGAFMVRDSRT-AGTYTVSVFTKAVVSEnnpcikhYHIKETNDNPKRYYVA---EKYVFDS 315
Cdd:cd10400   6 YHGKISRETGEKLLLAAGLDGSYLLRDSESvPGVYCLCVLYKGYVYT-------YRVSQTETGSWSAETApgvHKRLFRK 78
                        90       100
                ....*....|....*....|...
gi 15718680 316 IPLLINYHQHNGGGLVTRLRYPV 338
Cdd:cd10400  79 VKNLISAFQKPDQGIVTPLQYPV 101
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
466-553 1.32e-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: 60.05  E-value: 1.32e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 466 VCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVlDDQYTSSTGTKFpvkWASPEV-FSFSRYSSKSDVWSF 544
Cdd:cd07877 129 ILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHT-DDEMTGYVATRW---YRAPEImLNWMHYNQTVDIWSV 204

                ....*....
gi 15718680 545 GVLMWEVFS 553
Cdd:cd07877 205 GCIMAELLT 213
PTZ00036 PTZ00036
glycogen synthase kinase; Provisional
369-551 1.35e-09

glycogen synthase kinase; Provisional


Pssm-ID: 173333 [Multi-domain]  Cd Length: 440  Bit Score: 60.82  E-value: 1.35e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  369 IGSGQFGLVHLGYWLN-KDKVAIKTIREGAMSEEdfiEEAEVMMKLSHPKLVQL----YGVCLEQAP----ICLVFEFME 439
Cdd:PTZ00036  74 IGNGSFGVVYEAICIDtSEKVAIKKVLQDPQYKN---RELLIMKNLNHINIIFLkdyyYTECFKKNEknifLNVVMEFIP 150
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  440 ---HGCLSDYLRTQRGLFAAETLLgMCLDVCEGMAYLEEACVIHRDLAARNCLVGEN-QVIKVSDFGMTRFVLDDQYTSS 515
Cdd:PTZ00036 151 qtvHKYMKHYARNNHALPLFLVKL-YSYQLCRALAYIHSKFICHRDLKPQNLLIDPNtHTLKLCDFGSAKNLLAGQRSVS 229
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 15718680  516 -TGTKFpvkWASPEV-FSFSRYSSKSDVWSFGVLMWEV 551
Cdd:PTZ00036 230 yICSRF---YRAPELmLGATNYTTHIDLWSLGCIIAEM 264
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
404-571 1.48e-09

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: 59.60  E-value: 1.48e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 404 IEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGL-FAAETLLGMCLDVCEGMAYLEEACVIHRD 482
Cdd:cd05632  50 LNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIMNGGDLKFHIYNMGNPgFEEERALFYAAEILCGLEDLHRENTVYRD 129
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 483 LAARNCLVGENQVIKVSDFGMT-RFVLDDQYTSSTGTkfpVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFsEGKIPYEN 561
Cdd:cd05632 130 LKPENILLDDYGHIRISDLGLAvKIPEGESIRGRVGT---VGYMAPEVLNNQRYTLSPDYWGLGCLIYEMI-EGQSPFRG 205
                       170
                ....*....|
gi 15718680 562 RSNSEVVEDI 571
Cdd:cd05632 206 RKEKVKREEV 215
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
398-603 1.50e-09

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: 59.48  E-value: 1.50e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 398 MSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHG--CLSDYLRTQRGLFAAETLLGMCL-DVCEGMAYLE 474
Cdd:cd14094  47 LSTEDLKREASICHMLKHPHIVELLETYSSDGMLYMVFEFMDGAdlCFEIVKRADAGFVYSEAVASHYMrQILEALRYCH 126
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 475 EACVIHRDLAARNCLVG--ENQV-IKVSDFGMTRFVLDDQYTSSTGTKFPvKWASPEVFSFSRYSSKSDVWSFGVLMWEV 551
Cdd:cd14094 127 DNNIIHRDVKPHCVLLAskENSApVKLGGFGVAIQLGESGLVAGGRVGTP-HFMAPEVVKREPYGKPVDVWGCGVILFIL 205
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15718680 552 FSeGKIPYENrSNSEVVEDISTGFRLYKPRLAST---------------------HVYQIMNHCW-KERPEDRP 603
Cdd:cd14094 206 LS-GCLPFYG-TKERLFEGIIKGKYKMNPRQWSHisesakdlvrrmlmldpaeriTVYEALNHPWiKERDRYAY 277
STKc_ROCK cd05596
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
355-550 1.57e-09

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: 60.08  E-value: 1.57e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 355 KWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKV-AIKTIREGAM---SEEDFI-EEAEVMMKLSHPKLVQLYGVCLEQA 429
Cdd:cd05596  20 KLRMNAEDFDVIKVIGRGAFGEVQLVRHKSTKKVyAMKLLSKFEMikrSDSAFFwEERDIMAHANSEWIVQLHYAFQDDK 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 430 PICLVFEFMEHG----CLSDYLRTQR--GLFAAETLLGmcLDVCEGMAYleeacvIHRDLAARNCLVGENQVIKVSDFGM 503
Cdd:cd05596 100 YLYMVMDYMPGGdlvnLMSNYDVPEKwaRFYTAEVVLA--LDAIHSMGF------VHRDVKPDNMLLDASGHLKLADFGT 171
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 15718680 504 -TRFVLDDQYTSSTGTKFPvKWASPEVFS----FSRYSSKSDVWSFGVLMWE 550
Cdd:cd05596 172 cMKMDKDGLVRSDTAVGTP-DYISPEVLKsqggDGVYGRECDWWSVGVFLYE 222
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
25-103 1.72e-09

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 55.42  E-value: 1.72e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680  25 NFKVRFFVL--TKASLAYFEDRHGKKrtLKGSIELSRIKCVEIVKSDISIPCHY--KYPFQVVHDNYLLYVFAPDRESRQ 100
Cdd:cd01235  18 GWKQRWFVLdsTKHQLRYYESREDTK--CKGFIDLAEVESVTPATPIIGAPKRAdeGAFFDLKTNKRVYNFCAFDAESAQ 95

                ...
gi 15718680 101 RWV 103
Cdd:cd01235  96 QWI 98
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
239-338 1.84e-09

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 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: 198184  Cd Length: 104  Bit Score: 55.11  E-value: 1.84e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 239 WYNKSISRDKAEKLLLdtGK-EGAFMVRDSRTAGTYTVSVFTKAVVsennpciKHYHIKETndnPKRYYVAEKY-VFDSI 316
Cdd:cd09930   8 WLVGDINRTQAEELLR--GKpDGTFLIRESSTQGCYACSVVCNGEV-------KHCVIYKT---ETGYGFAEPYnLYESL 75
                        90       100
                ....*....|....*....|....*..
gi 15718680 317 PLLINYHQHNG-----GGLVTRLRYPV 338
Cdd:cd09930  76 KELVLHYAHNSleqhnDSLTVTLAYPV 102
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
369-602 2.16e-09

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes 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 region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 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: 270957 [Multi-domain]  Cd Length: 295  Bit Score: 58.93  E-value: 2.16e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK-----VAIKTIREGAMS----EEDFIEEAevmmKLSHPKLVQLY-----GVCLEQApICLV 434
Cdd:cd14055   3 VGKGRFAEVWKAKLKQNASgqyetVAVKIFPYEEYAswknEKDIFTDA----SLKHENILQFLtaeerGVGLDRQ-YWLI 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 435 FEFMEHGCLSDYLRtqRGLFAAETLLGMCLDVCEGMAYLEEAC---------VIHRDLAARNCLVGENQVIKVSDFGMTr 505
Cdd:cd14055  78 TAYHENGSLQDYLT--RHILSWEDLCKMAGSLARGLAHLHSDRtpcgrpkipIAHRDLKSSNILVKNDGTCVLADFGLA- 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 506 FVLD-----DQYTSS--TGTKfpvKWASPEVF----------SFSRysskSDVWSFGVLMWEVFSEGKI-----PYENRS 563
Cdd:cd14055 155 LRLDpslsvDELANSgqVGTA---RYMAPEALesrvnledleSFKQ----IDVYSMALVLWEMASRCEAsgevkPYELPF 227
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15718680 564 NSEVVE------------------DISTGFRLYKprlASTHVYQIMNHCWKERPEDR 602
Cdd:cd14055 228 GSKVRErpcvesmkdlvlrdrgrpEIPDSWLTHQ---GMCVLCDTITECWDHDPEAR 281
SH3_Eps8 cd11764
Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar ...
176-226 2.21e-09

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212698 [Multi-domain]  Cd Length: 54  Bit Score: 53.42  E-value: 2.21e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 15718680 176 VIALYDYQTNDPQELALRRNEEYCLLDSSEiHWWRVQDRNGHEGYVPSSYL 226
Cdd:cd11764   2 VRVLYDFTARNSKELSVLKGEYLEVLDDSR-QWWKVRNSRGQVGYVPHNIL 51
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
394-570 2.24e-09

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: 58.50  E-value: 2.24e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 394 REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQrGLFAAETLLGMCLDVCEGMAYL 473
Cdd:cd14088  37 RDGRKVRKAAKNEINILKMVKHPNILQLVDVFETRKEYFIFLELATGREVFDWILDQ-GYYSERDTSNVIRQVLEAVAYL 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 474 EEACVIHRDLAARNCLVG---ENQVIKVSDFGMTRfVLDDQYTSSTGTKfpvKWASPEVFSFSRYSSKSDVWSFGVLMWE 550
Cdd:cd14088 116 HSLKIVHRNLKLENLVYYnrlKNSKIVISDFHLAK-LENGLIKEPCGTP---EYLAPEVVGRQRYGRPVDCWAIGVIMYI 191
                       170       180
                ....*....|....*....|
gi 15718680 551 VFSeGKIPYENRSNSEVVED 570
Cdd:cd14088 192 LLS-GNPPFYDEAEEDDYEN 210
STKc_PRP4 cd14135
Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze ...
369-568 2.29e-09

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 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: 271037 [Multi-domain]  Cd Length: 318  Bit Score: 59.16  E-value: 2.29e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 369 IGSGQFGLVHLGYWLNKDK--VAIKTIREGAMSEEDFIEEAEVMMKLS--------HpkLVQLYGVCLEQAPICLVFEFM 438
Cdd:cd14135   8 LGKGVFSNVVRARDLARGNqeVAIKIIRNNELMHKAGLKELEILKKLNdadpddkkH--CIRLLRHFEHKNHLCLVFESL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15718680 439 eHGCLSDYLR----------TQRGLFAAETLLGMCLdvcegmayLEEACVIHRDLAARNCLVGENQ-VIKVSDFGMTRFV 507
Cdd:cd14135  86 -SMNLREVLKkygknvglniKAVRSYAQQLFLALKH--------LKKCNILHADIKPDNILVNEKKnTLKLCDFGSASDI 156
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15718680 508 LDDQYTSSTGTKFpvkWASPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVV 568
Cdd:cd14135 157 GENEITPYLVSRF---YRAPEIILGLPYDYPIDMWSVGCTLYELYT-GKILFPGKTNNHML 213
 
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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