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Conserved domains on  [gi|33469982|ref|NP_001706|]
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tyrosine-protein kinase Blk isoform 1 [Homo sapiens]

Protein Classification

protein kinase family protein( domain architecture ID 10186281)

protein kinase family protein containing Src homology 2 (SH2) domain(s), may catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine and/or tyrosine residues on protein substrates; similar to Syk-like subfamily of tyrosine-protein kinases

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
233-496 0e+00

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd05067:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 264  Bit Score: 513.67  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVT 312
Cdd:cd05067   1 EWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAIKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIIT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTA 391
Cdd:cd05067  81 EYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIeDNEYTA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:cd05067 161 REGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQ-LMRL 239
                       250       260
                ....*....|....*....|....*
gi 33469982 472 CWRSRPEERPTFEFLQSVLEDFYTA 496
Cdd:cd05067 240 CWKERPEDRPTFEYLRSVLEDFFTA 264
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
120-219 1.48e-73

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: 227.60  E-value: 1.48e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQGELIKHYKIRCLDEGGYYISPRITFPSLQ 199
Cdd:cd10371   1 EVEKWFFRTISRKDAERQLLAPMNKAGSFLIRESESNKGAFSLSVKDVTTQGEVVKHYKIRSLDNGGYYISPRITFPTLQ 80
                        90       100
                ....*....|....*....|
gi 33469982 200 ALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10371  81 ALVQHYSKKGDGLCQKLTLP 100
SH3_Blk cd12009
Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of ...
62-115 5.15e-31

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212942 [Multi-domain]  Cd Length: 54  Bit Score: 114.14  E-value: 5.15e-31
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVAR 115
Cdd:cd12009   1 CVIAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWLAKSLTTGKEGYIPSNYVAR 54
 
Name Accession Description Interval E-value
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
233-496 0e+00

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: 513.67  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVT 312
Cdd:cd05067   1 EWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAIKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIIT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTA 391
Cdd:cd05067  81 EYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIeDNEYTA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:cd05067 161 REGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQ-LMRL 239
                       250       260
                ....*....|....*....|....*
gi 33469982 472 CWRSRPEERPTFEFLQSVLEDFYTA 496
Cdd:cd05067 240 CWKERPEDRPTFEYLRSVLEDFFTA 264
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
241-490 4.51e-135

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: 390.70  E-value: 4.51e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   241 LRLVRKLGSGQFGEVWMGYYK-----NNMKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVT 312
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKgegenTKIKVAVKTLKEGADEEerEDFLEEASIMKKLDHPNIVKLLGVCTQgEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   313 EYMARGCLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEYT 390
Cdd:pfam07714  81 EYMPGGDLLDFLR-KHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIydDDYYR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   391 AQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIA 470
Cdd:pfam07714 160 KRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYD-LMK 238
                         250       260
                  ....*....|....*....|
gi 33469982   471 ECWRSRPEERPTFEFLQSVL 490
Cdd:pfam07714 239 QCWAYDPEDRPTFSELVEDL 258
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
241-490 8.60e-122

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: 356.86  E-value: 8.60e-122
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    241 LRLVRKLGSGQFGEVWMGYYKNN-----MKVAIKTLKEGTMS--PEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVT 312
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGKgdgkeVEVAVKTLKEDASEqqIEEFLREARIMRKLDHPNIVKLLGVCTEeEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    313 EYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS-EYTA 391
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDdDYYK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:smart00221 161 VKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYK-LMLQ 239
                          250
                   ....*....|....*....
gi 33469982    472 CWRSRPEERPTFEFLQSVL 490
Cdd:smart00221 240 CWAEDPEDRPTFSELVEIL 258
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
120-219 1.48e-73

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: 227.60  E-value: 1.48e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQGELIKHYKIRCLDEGGYYISPRITFPSLQ 199
Cdd:cd10371   1 EVEKWFFRTISRKDAERQLLAPMNKAGSFLIRESESNKGAFSLSVKDVTTQGEVVKHYKIRSLDNGGYYISPRITFPTLQ 80
                        90       100
                ....*....|....*....|
gi 33469982 200 ALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10371  81 ALVQHYSKKGDGLCQKLTLP 100
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
242-481 2.08e-43

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 160.18  E-value: 2.08e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKN-NMKVAIKTLK-EGTMSPEA---FLGEANVMKALQHERLVRLYAVVTKEPI-YIVTEYM 315
Cdd:COG0515  10 RILRLLGRGGMGVVYLARDLRlGRPVALKVLRpELAADPEArerFRREARALARLNHPNIVRVYDVGEEDGRpYLVMEYV 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGA 395
Cdd:COG0515  90 EGESLADLLR--RRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGT 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 kfpIKWT----APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMP----RPDtCPPELyRG 467
Cdd:COG0515 168 ---VVGTpgymAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPPpselRPD-LPPAL-DA 241
                       250
                ....*....|....
gi 33469982 468 VIAECWRSRPEERP 481
Cdd:COG0515 242 IVLRALAKDPEERY 255
SH3_Blk cd12009
Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of ...
62-115 5.15e-31

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212942 [Multi-domain]  Cd Length: 54  Bit Score: 114.14  E-value: 5.15e-31
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVAR 115
Cdd:cd12009   1 CVIAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWLAKSLTTGKEGYIPSNYVAR 54
SH2 pfam00017
SH2 domain;
124-205 9.58e-30

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 111.15  E-value: 9.58e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   124 WFFRSQGRKEAERQLLApINKAGSFLIRESETNKGAFSLSVKDvttqGELIKHYKIRCLDEGGYYISPRITFPSLQALVQ 203
Cdd:pfam00017   1 WYHGKISRQEAERLLLN-GKPDGTFLVRESESTPGGYTLSVRD----DGKVKHYKIQSTDNGGYYISGGVKFSSLAELVE 75

                  ..
gi 33469982   204 HY 205
Cdd:pfam00017  76 HY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
122-211 1.39e-25

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: 100.00  E-value: 1.39e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    122 ERWFFRSQGRKEAERQLLAPINkaGSFLIRESETNKGAFSLSVKDvttqGELIKHYKIRCLDEGGYYISPRITFPSLQAL 201
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEGD--GDFLVRDSESSPGDYVLSVRV----KGKVKHYRIRRNEDGKFYLEGGRKFPSLVEL 74
                           90
                   ....*....|
gi 33469982    202 VQHYSKKGDG 211
Cdd:smart00252  75 VEHYQKNSLG 84
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
242-438 1.98e-20

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 94.48  E-value: 1.98e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  242 RLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPEAFL----GEANVMKALQHERLVRLYAVVTKEPI-YIVTEYM 315
Cdd:NF033483  10 EIGERIGRGGMAEVYLAKdTRLDRDVAVKVLRPDLARDPEFVarfrREAQSAASLSHPNIVSVYDVGEDGGIpYIVMEYV 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  316 ArGCLL-DFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEG 394
Cdd:NF033483  90 D-GRTLkDYIR--EHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSTTMTQTN 166
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 33469982  395 AkfpIKWTA----PEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:NF033483 167 S---VLGTVhylsPEQARGGTVDARSDIYSLGIVLYEMLT-GRPPFDG 210
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
247-465 2.56e-17

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 82.89  E-value: 2.56e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  247 LGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPEAF---------------LGEANVMKALQHERLVRLYAV-VTKEPIY 309
Cdd:PTZ00024  17 LGEGTYGKVEKAYDTLTGKiVAIKKVKIIEISNDVTkdrqlvgmcgihfttLRELKIMNEIKHENIMGLVDVyVEGDFIN 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  310 IVTEYMARgcllDFLKT-DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR----- 383
Cdd:PTZ00024  97 LVMDIMAS----DLKKVvDRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLARrygyp 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  384 IIDSEYTAQEGAKFPIKWT---------APEAIhFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSNpevIRNLERGY 452
Cdd:PTZ00024 173 PYSDTLSKDETMQRREEMTskvvtlwyrAPELL-MGAekYHFAVDMWSVGCIFAELLT-GKPLFPGENE---IDQLGRIF 247
                        250
                 ....*....|....*.
gi 33469982  453 RM---PRPDTCPPELY 465
Cdd:PTZ00024 248 ELlgtPNEDNWPQAKK 263
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
59-114 1.80e-15

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: 70.64  E-value: 1.80e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982     59 DKHFVVALYDYTAMNDRDLQMLKGEKLQVL-KGTGDWWLARsLVTGREGYVPSNFVA 114
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLeKSDDGWWKGR-LGRGKEGLFPSNYVE 56
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
64-110 1.80e-13

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: 64.53  E-value: 1.80e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 33469982    64 VALYDYTAMNDRDLQMLKGEKLQVL-KGTGDWWLARSLvTGREGYVPS 110
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLeKSEDGWWKGRNK-GGKEGLIPS 47
 
Name Accession Description Interval E-value
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
233-496 0e+00

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: 513.67  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVT 312
Cdd:cd05067   1 EWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAIKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIIT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTA 391
Cdd:cd05067  81 EYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIeDNEYTA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:cd05067 161 REGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQ-LMRL 239
                       250       260
                ....*....|....*....|....*
gi 33469982 472 CWRSRPEERPTFEFLQSVLEDFYTA 496
Cdd:cd05067 240 CWKERPEDRPTFEYLRSVLEDFFTA 264
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
234-502 6.62e-174

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: 490.32  E-value: 6.62e-174
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVT 312
Cdd:cd05072   2 WEIPRESIKLVKKLGAGQFGEVWMGYYNNSTKVAVKTLKPGTMSVQAFLEEANLMKTLQHDKLVRLYAVVTKeEPIYIIT 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTA 391
Cdd:cd05072  82 EYMAKGSLLDFLKSDEGGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIeDNEYTA 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:cd05072 162 REGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYD-IMKT 240
                       250       260       270
                ....*....|....*....|....*....|.
gi 33469982 472 CWRSRPEERPTFEFLQSVLEDFYTATERQYE 502
Cdd:cd05072 241 CWKEKAEERPTFDYLQSVLDDFYTATEGQYQ 271
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
245-491 2.30e-171

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: 482.55  E-value: 2.30e-171
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVTEYMARGCLLDF 323
Cdd:cd05034   1 KKLGAGQFGEVWMGVWNGTTKVAVKTLKPGTMSPEAFLQEAQIMKKLRHDKLVQLYAVCSDeEPIYIVTELMSKGSLLDY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTAQEGAKFPIKWT 402
Cdd:cd05034  81 LRTGEGRALRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIeDDEYTAREGAKFPIKWT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 403 APEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPEERPT 482
Cdd:cd05034 161 APEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYD-IMLQCWKKEPEERPT 239

                ....*....
gi 33469982 483 FEFLQSVLE 491
Cdd:cd05034 240 FEYLQSFLE 248
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
229-493 1.69e-156

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: 445.62  E-value: 1.69e-156
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 229 WAQDEWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPI 308
Cdd:cd05073   1 WEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 YIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DS 387
Cdd:cd05073  81 YIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIeDN 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYrG 467
Cdd:cd05073 161 EYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELY-N 239
                       250       260
                ....*....|....*....|....*.
gi 33469982 468 VIAECWRSRPEERPTFEFLQSVLEDF 493
Cdd:cd05073 240 IMMRCWKNRPEERPTFEYIQSVLDDF 265
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
232-495 3.88e-154

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: 439.92  E-value: 3.88e-154
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 232 DEWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVT-KEPIYI 310
Cdd:cd05068   1 DQWEIDRKSLKLLRKLGSGQFGEVWEGLWNNTTPVAVKTLKPGTMDPEDFLREAQIMKKLRHPKLIQLYAVCTlEEPIYI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSE 388
Cdd:cd05068  81 ITELMKHGSLLEYLQ-GKGRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIkvEDE 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgV 468
Cdd:cd05068 160 YEAREGAKFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYD-I 238
                       250       260
                ....*....|....*....|....*..
gi 33469982 469 IAECWRSRPEERPTFEFLQSVLEDFYT 495
Cdd:cd05068 239 MLECWKADPMERPTFETLQWKLEDFFV 265
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
245-492 2.02e-145

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: 417.01  E-value: 2.02e-145
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARGCLLDFL 324
Cdd:cd14203   1 VKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMSPEAFLEEAQIMKKLRHDKLVQLYAVVSEEPIYIVTEFMSKGSLLDFL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 325 KTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTAQEGAKFPIKWTA 403
Cdd:cd14203  81 KDGEGKYLKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIeDNEYTARQGAKFPIKWTA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 404 PEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTF 483
Cdd:cd14203 161 PEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHE-LMCQCWRKDPEERPTF 239

                ....*....
gi 33469982 484 EFLQSVLED 492
Cdd:cd14203 240 EYLQSFLED 248
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
231-502 4.51e-138

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: 399.44  E-value: 4.51e-138
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 231 QDEWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYI 310
Cdd:cd05070   1 KDVWEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEY 389
Cdd:cd05070  81 VTEYMSKGSLLDFLKDGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIeDNEY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRGVI 469
Cdd:cd05070 161 TARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMI 240
                       250       260       270
                ....*....|....*....|....*....|...
gi 33469982 470 aECWRSRPEERPTFEFLQSVLEDFYTATERQYE 502
Cdd:cd05070 241 -HCWKKDPEERPTFEYLQGFLEDYFTATEPQYQ 272
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
230-502 2.19e-137

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: 397.52  E-value: 2.19e-137
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 230 AQDEWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIY 309
Cdd:cd05069   3 AKDAWEIPRESLRLDVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIY 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 310 IVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSE 388
Cdd:cd05069  83 IVTEFMGKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIeDNE 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgV 468
Cdd:cd05069 163 YTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCPESLHE-L 241
                       250       260       270
                ....*....|....*....|....*....|....
gi 33469982 469 IAECWRSRPEERPTFEFLQSVLEDFYTATERQYE 502
Cdd:cd05069 242 MKLCWKKDPDERPTFEYIQSFLEDYFTATEPQYQ 275
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
241-490 4.51e-135

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: 390.70  E-value: 4.51e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   241 LRLVRKLGSGQFGEVWMGYYK-----NNMKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVT 312
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKgegenTKIKVAVKTLKEGADEEerEDFLEEASIMKKLDHPNIVKLLGVCTQgEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   313 EYMARGCLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEYT 390
Cdd:pfam07714  81 EYMPGGDLLDFLR-KHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIydDDYYR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   391 AQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIA 470
Cdd:pfam07714 160 KRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYD-LMK 238
                         250       260
                  ....*....|....*....|
gi 33469982   471 ECWRSRPEERPTFEFLQSVL 490
Cdd:pfam07714 239 QCWAYDPEDRPTFSELVEDL 258
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
231-502 5.13e-134

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: 389.05  E-value: 5.13e-134
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 231 QDEWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYI 310
Cdd:cd05071   1 KDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEY 389
Cdd:cd05071  81 VTEYMSKGSLLDFLKGEMGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIeDNEY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVI 469
Cdd:cd05071 161 TARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHD-LM 239
                       250       260       270
                ....*....|....*....|....*....|...
gi 33469982 470 AECWRSRPEERPTFEFLQSVLEDFYTATERQYE 502
Cdd:cd05071 240 CQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQ 272
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
241-490 8.60e-122

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: 356.86  E-value: 8.60e-122
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    241 LRLVRKLGSGQFGEVWMGYYKNN-----MKVAIKTLKEGTMS--PEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVT 312
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGKgdgkeVEVAVKTLKEDASEqqIEEFLREARIMRKLDHPNIVKLLGVCTEeEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    313 EYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS-EYTA 391
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDdDYYK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:smart00221 161 VKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYK-LMLQ 239
                          250
                   ....*....|....*....
gi 33469982    472 CWRSRPEERPTFEFLQSVL 490
Cdd:smart00221 240 CWAEDPEDRPTFSELVEIL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
241-490 2.82e-120

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 352.99  E-value: 2.82e-120
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    241 LRLVRKLGSGQFGEVWMGYYKNN-----MKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVT 312
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKGKggkkkVEVAVKTLKEDASEQqiEEFLREARIMRKLDHPNVVKLLGVCTEeEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    313 EYMARGCLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS-EYTA 391
Cdd:smart00219  81 EYMEGGDLLSYLR-KNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDdDYYR 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:smart00219 160 KRGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYD-LMLQ 238
                          250
                   ....*....|....*....
gi 33469982    472 CWRSRPEERPTFEFLQSVL 490
Cdd:smart00219 239 CWAEDPEDRPTFSELVEIL 257
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
245-491 1.94e-118

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: 348.76  E-value: 1.94e-118
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNN----MKVAIKTLKEGTMSPE--AFLGEANVMKALQHERLVRLYAVVT-KEPIYIVTEYMAR 317
Cdd:cd00192   1 KKLGEGAFGEVYKGKLKGGdgktVDVAVKTLKEDASESErkDFLKEARVMKKLGHPNVVRLLGVCTeEEPLYLVMEYMEG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKT-------DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE-- 388
Cdd:cd00192  81 GDLLDFLRKsrpvfpsPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDdy 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgV 468
Cdd:cd00192 161 YRKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYE-L 239
                       250       260
                ....*....|....*....|...
gi 33469982 469 IAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd00192 240 MLSCWQLDPEDRPTFSELVERLE 262
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
234-493 4.15e-113

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: 335.17  E-value: 4.15e-113
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIV 311
Cdd:cd05148   1 WERPREEFTLERKLGSGYFGEVWEGLWKNRVRVAIKILKsDDLLKQQDFQKEVQALKRLRHKHLISLFAVCSVgEPVYII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd05148  81 TELMEKGSLLAFLRSPEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKEDVYL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:cd05148 161 SSDKKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYK-IMLE 239
                       250       260
                ....*....|....*....|..
gi 33469982 472 CWRSRPEERPTFEFLQSVLEDF 493
Cdd:cd05148 240 CWAAEPEDRPSFKALREELDNI 261
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
234-491 6.53e-106

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: 316.60  E-value: 6.53e-106
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKNNmKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVT 312
Cdd:cd05039   1 WAINKKDLKLGELIGKGEFGDVMLGDYRGQ-KVAVKCLKDDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGnGLYIVT 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiiDSEYTaQ 392
Cdd:cd05039  80 EYMAKGSLVDYLRSRGRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAK--EASSN-Q 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAEC 472
Cdd:cd05039 157 DGGKLPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYK-VMKNC 235
                       250
                ....*....|....*....
gi 33469982 473 WRSRPEERPTFEFLQSVLE 491
Cdd:cd05039 236 WELDPAKRPTFKQLREKLE 254
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
236-490 6.31e-104

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: 311.30  E-value: 6.31e-104
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEY 314
Cdd:cd05059   1 IDPSELTFLKELGSGQFGVVHLGKWRGKIDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQrPIFIVTEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR-IIDSEYTAQE 393
Cdd:cd05059  81 MANGCLLNYLRERRG-KFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARyVLDDEYTSSV 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECW 473
Cdd:cd05059 160 GTKFPVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYT-IMYSCW 238
                       250
                ....*....|....*..
gi 33469982 474 RSRPEERPTFEFLQSVL 490
Cdd:cd05059 239 HEKPEERPTFKILLSQL 255
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
234-494 1.19e-98

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: 298.18  E-value: 1.19e-98
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIV 311
Cdd:cd05052   1 WEIERTDITMKHKLGGGQYGEVYEGVWKKyNLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREpPFYII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYT 390
Cdd:cd05052  81 TEFMPYGNLLDYLRECNREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMtGDTYT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 391 AQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIA 470
Cdd:cd05052 161 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYE-LMR 239
                       250       260
                ....*....|....*....|....
gi 33469982 471 ECWRSRPEERPTFEFLQSVLEDFY 494
Cdd:cd05052 240 ACWQWNPSDRPSFAEIHQALETMF 263
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
241-486 1.77e-93

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: 284.54  E-value: 1.77e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMARGC 319
Cdd:cd05112   6 LTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQaPICLVFEFMEHGC 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTAQEGAKFP 398
Cdd:cd05112  86 LSDYLRTQRGL-FSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVlDDQYTSSTGTKFP 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 IKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPE 478
Cdd:cd05112 165 VKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYE-IMNHCWKERPE 243

                ....*...
gi 33469982 479 ERPTFEFL 486
Cdd:cd05112 244 DRPSFSLL 251
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
236-493 1.13e-86

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: 267.70  E-value: 1.13e-86
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYKNNMK----VAIKTLKEGTmSPEA---FLGEANVMKALQHERLVRLYAVVTK-EP 307
Cdd:cd05033   1 IDASYVTIEKVIGGGEFGEVCSGSLKLPGKkeidVAIKTLKSGY-SDKQrldFLTEASIMGQFDHPNVIRLEGVVTKsRP 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-- 385
Cdd:cd05033  80 VMIVTEYMENGSLDKFLRENDG-KFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLed 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 -DSEYTAQeGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPEL 464
Cdd:cd05033 159 sEATYTTK-GGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSAL 237
                       250       260
                ....*....|....*....|....*....
gi 33469982 465 YRgVIAECWRSRPEERPTFEFLQSVLEDF 493
Cdd:cd05033 238 YQ-LMLDCWQKDRNERPTFSQIVSTLDKM 265
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
245-490 4.28e-86

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: 265.46  E-value: 4.28e-86
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTLKEgTMSPE---AFLGEANVMKALQHERLVRLYAV-VTKEPIYIVTEYMARGC 319
Cdd:cd05041   1 EKIGRGNFGDVYRGVLKpDNTEVAVKTCRE-TLPPDlkrKFLQEARILKQYDHPNIVKLIGVcVQKQPIMIVMELVPGGS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI-IDSEYTAQEGAK-F 397
Cdd:cd05041  80 LLTFLRK-KGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREeEDGEYTVSDGLKqI 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 398 PIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRP 477
Cdd:cd05041 159 PIKWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYR-LMLQCWAYDP 237
                       250
                ....*....|...
gi 33469982 478 EERPTFEFLQSVL 490
Cdd:cd05041 238 ENRPSFSEIYNEL 250
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
241-492 2.91e-83

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: 258.64  E-value: 2.91e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMARGC 319
Cdd:cd05114   6 LTFMKELGSGLFGVVRLGKWRAQYKVAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQkPIYIVTEFMENGC 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR-IIDSEYTAQEGAKFP 398
Cdd:cd05114  86 LLNYLRQRRG-KLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRyVLDDQYTSSSGAKFP 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 IKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPE 478
Cdd:cd05114 165 VKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYE-VMYSCWHEKPE 243
                       250
                ....*....|....
gi 33469982 479 ERPTFEFLQSVLED 492
Cdd:cd05114 244 GRPTFADLLRTITE 257
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
236-491 9.36e-83

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: 257.12  E-value: 9.36e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEY 314
Cdd:cd05113   1 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQrPIFIITEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR-IIDSEYTAQE 393
Cdd:cd05113  81 MANGCLLNYLR-EMRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRyVLDDEYTSSV 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECW 473
Cdd:cd05113 160 GSKFPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYT-IMYSCW 238
                       250
                ....*....|....*...
gi 33469982 474 RSRPEERPTFEFLQSVLE 491
Cdd:cd05113 239 HEKADERPTFKILLSNIL 256
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
234-492 1.54e-82

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: 256.45  E-value: 1.54e-82
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKNNmKVAIKTLKEGTmSPEAFLGEANVMKALQHERLVRLYAVVTKEP--IYIV 311
Cdd:cd05082   1 WALNMKELKLLQTIGKGEFGDVMLGDYRGN-KVAVKCIKNDA-TAQAFLAEASVMTQLRHSNLVQLLGVIVEEKggLYIV 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSeytA 391
Cdd:cd05082  79 TEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASS---T 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:cd05082 156 QDTGKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYD-VMKN 234
                       250       260
                ....*....|....*....|.
gi 33469982 472 CWRSRPEERPTFEFLQSVLED 492
Cdd:cd05082 235 CWHLDAAMRPSFLQLREQLEH 255
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
234-492 2.48e-79

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: 249.18  E-value: 2.48e-79
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKN------NMKVAIKTLKEGTMSPE--AFLGEANVMKALQHERLVRLYAVVTK 305
Cdd:cd05032   1 WELPREKITLIRELGQGSFGMVYEGLAKGvvkgepETRVAIKTVNENASMREriEFLNEASVMKEFNCHHVVRLLGVVST 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 E-PIYIVTEYMARGCLLDFLK--------TDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKI 376
Cdd:cd05032  81 GqPTLVVMELMAKGDLKSYLRsrrpeaenNPGLGPPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 377 ADFGLAR-IIDSEYTAQEG-AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRM 454
Cdd:cd05032 161 GDFGMTRdIYETDYYRKGGkGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGHL 240
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 33469982 455 PRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd05032 241 DLPENCPDKLLE-LMRMCWQYNPKMRPTFLEIVSSLKD 277
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
245-494 1.12e-78

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: 246.49  E-value: 1.12e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYY--KNN--MKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARG 318
Cdd:cd05060   1 KELGHGNFGSVRKGVYlmKSGkeVEVAVKTLKQEHEKAgkKEFLREASVMAQLDHPCIVRLIGVCKGEPLMLVMELAPLG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII---DSEYTAQEGA 395
Cdd:cd05060  81 PLLKYLKKR--REIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALgagSDYYRATTAG 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRS 475
Cdd:cd05060 159 RWPLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYS-IMLSCWKY 237
                       250
                ....*....|....*....
gi 33469982 476 RPEERPTFEFLQSVLEDFY 494
Cdd:cd05060 238 RPEDRPTFSELESTFRRDP 256
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
234-491 1.38e-77

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: 243.63  E-value: 1.38e-77
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKNNmKVAIKTLKeGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTE 313
Cdd:cd05083   1 WLLNLQKLTLGEIIGEGEFGAVLQGEYMGQ-KVAVKNIK-CDVTAQAFLEETAVMTKLQHKNLVRLLGVILHNGLYIVME 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIidsEYTAQE 393
Cdd:cd05083  79 LMSKGNLVNFLRSRGRALVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKV---GSMGVD 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYrGVIAECW 473
Cdd:cd05083 156 NSRLPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVY-SIMTSCW 234
                       250
                ....*....|....*...
gi 33469982 474 RSRPEERPTFEFLQSVLE 491
Cdd:cd05083 235 EAEPGKRPSFKKLREKLE 252
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
247-490 2.69e-76

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: 240.13  E-value: 2.69e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCLLD 322
Cdd:cd13999   1 IGSGSFGEVYKGKWRGT-DVAIKKLKVEDDNDellKEFRREVSILSKLRHPNIVQFIGACLSPPpLCIVTEYMPGGSLYD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPIKWT 402
Cdd:cd13999  80 LL-HKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKNSTTEKMTGVVGTPRWM 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 403 APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVI-RNLERGYRMPRPDTCPPELYRgVIAECWRSRPEERP 481
Cdd:cd13999 159 APEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIAaAVVQKGLRPPIPPDCPPELSK-LIKRCWNEDPEKRP 236

                ....*....
gi 33469982 482 TFEFLQSVL 490
Cdd:cd13999 237 SFSEIVKRL 245
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
246-492 8.84e-76

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: 239.17  E-value: 8.84e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNN----MKVAIKTLKEGTMS----PEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMAR 317
Cdd:cd05040   2 KLGDGSFGVVRRGEWTTPsgkvIQVAVKCLKSDVLSqpnaMDDFLKEVNAMHSLDHPNLIRLYGVVLSSPLMMVTELAPL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE---YTAQEG 394
Cdd:cd05040  82 GSLLDRLR-KDQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQNedhYVMQEH 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLER-GYRMPRPDTCPPELYRgVIAECW 473
Cdd:cd05040 161 RKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDKeGERLERPDDCPQDIYN-VMLQCW 239
                       250
                ....*....|....*....
gi 33469982 474 RSRPEERPTFEFLQSVLED 492
Cdd:cd05040 240 AHKPADRPTFVALRDFLPE 258
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
234-494 9.19e-76

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: 239.63  E-value: 9.19e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKN----NMKVAIKTLKEGTmSP---EAFLGEANVMKALQHERLVRLYAVVTKE 306
Cdd:cd05056   1 YEIQREDITLGRCIGEGQFGDVYQGVYMSpeneKIAVAVKTCKNCT-SPsvrEKFLQEAYIMRQFDHPHIVKLIGVITEN 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 PIYIVTEYMARGCLLDFLKTdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID 386
Cdd:cd05056  80 PVWIVMELAPLGELRSYLQV-NKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYME 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SE--YTAQEGaKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPEL 464
Cdd:cd05056 159 DEsyYKASKG-KLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTL 237
                       250       260       270
                ....*....|....*....|....*....|
gi 33469982 465 YrGVIAECWRSRPEERPTFEFLQSVLEDFY 494
Cdd:cd05056 238 Y-SLMTKCWAYDPSKRPRFTELKAQLSDIL 266
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
233-483 1.88e-75

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: 239.63  E-value: 1.88e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEVWMGYY-------KNNMKVAIKTLKEGTMSPEA--FLGEANVMKAL-QHERLVRLYAV 302
Cdd:cd05053   6 EWELPRDRLTLGKPLGEGAFGQVVKAEAvgldnkpNEVVTVAVKMLKDDATEKDLsdLVSEMEMMKMIgKHKNIINLLGA 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 303 VTKE-PIYIVTEYMARGCLLDFLKTDE--------------GSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANIL 367
Cdd:cd05053  86 CTQDgPLYVVVEYASKGNLREFLRARRppgeeaspddprvpEEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAARNVL 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 368 VSEALCCKIADFGLARIIDSE--YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVI 445
Cdd:cd05053 166 VTEDNVMKIADFGLARDIHHIdyYRKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELF 245
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 33469982 446 RNLERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTF 483
Cdd:cd05053 246 KLLKEGHRMEKPQNCTQELYM-LMRDCWHEVPSQRPTF 282
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
247-492 5.59e-75

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: 237.31  E-value: 5.59e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKN-------NMKVAIKTLKEGTMSPE--AFLGEANVMKALQHERLVRLYAV-VTKEPIYIVTEYMA 316
Cdd:cd05044   3 LGSGAFGEVFEGTAKDilgdgsgETKVAVKTLRKGATDQEkaEFLKEAHLMSNFKHPNILKLLGVcLDNDPQYIILELME 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLK-----TDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCC----KIADFGLAR-IID 386
Cdd:cd05044  83 GGDLLSYLRaarptAFTPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSKDYRervvKIGDFGLARdIYK 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SEYTAQEG-AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELY 465
Cdd:cd05044 163 NDYYRKEGeGLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAGGRLDQPDNCPDDLY 242
                       250       260
                ....*....|....*....|....*..
gi 33469982 466 RgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd05044 243 E-LMLRCWSTDPEERPSFARILEQLQN 268
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
120-219 1.48e-73

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: 227.60  E-value: 1.48e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQGELIKHYKIRCLDEGGYYISPRITFPSLQ 199
Cdd:cd10371   1 EVEKWFFRTISRKDAERQLLAPMNKAGSFLIRESESNKGAFSLSVKDVTTQGEVVKHYKIRSLDNGGYYISPRITFPTLQ 80
                        90       100
                ....*....|....*....|
gi 33469982 200 ALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10371  81 ALVQHYSKKGDGLCQKLTLP 100
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
241-491 3.71e-73

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: 232.83  E-value: 3.71e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYK----NNMKVAIKTLKEGTMSPEA--FLGEANVMKALQHERLVRLYAVVTK-EPIYIVTE 313
Cdd:cd05066   6 IKIEKVIGAGEFGEVCSGRLKlpgkREIPVAIKTLKAGYTEKQRrdFLSEASIMGQFDHPNIIHLEGVVTRsKPVMIVTE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII----DSEY 389
Cdd:cd05066  86 YMENGSLDAFLRKHDG-QFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLeddpEAAY 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQeGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVI 469
Cdd:cd05066 165 TTR-GGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQ-LM 242
                       250       260
                ....*....|....*....|..
gi 33469982 470 AECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05066 243 LDCWQKDRNERPKFEQIVSILD 264
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
235-491 6.80e-73

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: 232.28  E-value: 6.80e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYY------KNNMKVAIKTLKEgTMSPEA---FLGEANVMKALQHERLVRLYAVVTK 305
Cdd:cd05036   2 EVPRKNLTLIRALGQGAFGEVYEGTVsgmpgdPSPLQVAVKTLPE-LCSEQDemdFLMEALIMSKFNHPNIVRCIGVCFQ 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 E-PIYIVTEYMARGCLLDFL-----KTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEAL---CCKI 376
Cdd:cd05036  81 RlPRFILLELMAGGDLKSFLrenrpRPEQPSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCKGpgrVAKI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 377 ADFGLAR-IIDSEYTAQEG-AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRM 454
Cdd:cd05036 161 GDFGMARdIYRADYYRKGGkAMLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSGGRM 240
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 33469982 455 PRPDTCPPELYRgVIAECWRSRPEERPTFEflqSVLE 491
Cdd:cd05036 241 DPPKNCPGPVYR-IMTQCWQHIPEDRPNFS---TILE 273
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
235-491 1.47e-71

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: 228.70  E-value: 1.47e-71
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYYK----NNMKVAIKTLKEGTMSPEA--FLGEANVMKALQHERLVRLYAVVTK-EP 307
Cdd:cd05063   1 EIHPSHITKQKVIGAGEFGEVFRGILKmpgrKEVAVAIKTLKPGYTEKQRqdFLSEASIMGQFSHHNIIRLEGVVTKfKP 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGSRLSLpRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS 387
Cdd:cd05063  81 AMIITEYMENGALDKYLRDHDGEFSSY-QLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLED 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 E----YTAQeGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPE 463
Cdd:cd05063 160 DpegtYTTS-GGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSA 238
                       250       260
                ....*....|....*....|....*...
gi 33469982 464 LYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05063 239 VYQ-LMLQCWQQDRARRPRFVDIVNLLD 265
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
235-493 2.94e-71

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: 228.07  E-value: 2.94e-71
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYY-----KNNMKVAIKTLKEGT--MSPEAFLGEANVMKALQHERLVRLYAVVTKEP 307
Cdd:cd05057   3 IVKETELEKGKVLGSGAFGTVYKGVWipegeKVKIPVAIKVLREETgpKANEEILDEAYVMASVDHPHLVRLLGICLSSQ 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID- 386
Cdd:cd05057  83 VQLITQLMPLGCLLDYVRNHRD-NIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLDv 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 --SEYTAqEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPEL 464
Cdd:cd05057 162 deKEYHA-EGGKVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDV 240
                       250       260
                ....*....|....*....|....*....
gi 33469982 465 YRgVIAECWRSRPEERPTFEFLQSVLEDF 493
Cdd:cd05057 241 YM-VLVKCWMIDAESRPTFKELANEFSKM 268
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
234-492 3.19e-71

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: 228.91  E-value: 3.19e-71
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEV------WMGYYKNNMKVAIKTLKEGTMSPE--AFLGEANVMKAL-QHERLVRLYAVVT 304
Cdd:cd05055  30 WEFPRNNLSFGKTLGAGAFGKVveatayGLSKSDAVMKVAVKMLKPTAHSSEreALMSELKIMSHLgNHENIVNLLGACT 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 305 KE-PIYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR 383
Cdd:cd05055 110 IGgPILVITEYCCYGDLLNFLRRKRESFLTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKICDFGLAR 189
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 384 II--DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMS-NPEVIRNLERGYRMPRPDTC 460
Cdd:cd05055 190 DImnDSNYVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMPvDSKFYKLIKEGYRMAQPEHA 269
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 461 PPELYRgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd05055 270 PAEIYD-IMKTCWDADPLKRPTFKQIVQLIGK 300
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
247-493 3.40e-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: 225.13  E-value: 3.40e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK----VAIKTLKEGTMSPEA--FLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMARGC 319
Cdd:cd05065  12 IGAGEFGEVCRGRLKLPGKreifVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNIIHLEGVVTKSrPVMIITEFMENGA 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-----DSEYTAQEG 394
Cdd:cd05065  92 LDSFLRQNDG-QFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddtsDPTYTSSLG 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWR 474
Cdd:cd05065 171 GKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTALHQ-LMLDCWQ 249
                       250
                ....*....|....*....
gi 33469982 475 SRPEERPTFEFLQSVLEDF 493
Cdd:cd05065 250 KDRNLRPKFGQIVNTLDKM 268
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
246-490 1.52e-69

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: 222.88  E-value: 1.52e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYK-NNMKVAIKTLKEgTMSPE---AFLGEANVMKALQHERLVRLYAVVT-KEPIYIVTEYMARGCL 320
Cdd:cd05084   3 RIGRGNFGEVFSGRLRaDNTPVAVKSCRE-TLPPDlkaKFLQEARILKQYSHPNIVRLIGVCTqKQPIYIVMELVQGGDF 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI-IDSEYTAQEGAK-FP 398
Cdd:cd05084  82 LTFLRT-EGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSREeEDGVYAATGGMKqIP 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 IKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPE 478
Cdd:cd05084 161 VKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYR-LMEQCWEYDPR 239
                       250
                ....*....|..
gi 33469982 479 ERPTFEFLQSVL 490
Cdd:cd05084 240 KRPSFSTVHQDL 251
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
247-490 1.97e-69

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: 222.57  E-value: 1.97e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEA--FLGEANVMKALQHERLVRLYAVVT-KEPIYIVTEYMARGCLLDF 323
Cdd:cd05085   4 LGKGNFGEVYKGTLKDKTPVAVKTCKEDLPQELKikFLSEARILKQYDHPNIVKLIGVCTqRQPIYIVMELVPGGDFLSF 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 L--KTDEgsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAK-FPIK 400
Cdd:cd05085  84 LrkKKDE---LKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRQEDDGVYSSSGLKqIPIK 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 WTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPEER 480
Cdd:cd05085 161 WTAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYK-IMQRCWDYNPENR 239
                       250
                ....*....|
gi 33469982 481 PTFEFLQSVL 490
Cdd:cd05085 240 PKFSELQKEL 249
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
235-483 9.49e-67

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: 216.47  E-value: 9.49e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMG--YYKNN----MKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLYAVVTKE 306
Cdd:cd05048   1 EIPLSAVRFLEELGEGAFGKVYKGelLGPSSeesaISVAIKTLKENASPKtqQDFRREAELMSDLQHPNIVCLLGVCTKE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 -PIYIVTEYMARGCLLDFL--------------KTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA 371
Cdd:cd05048  81 qPQCMLFEYMAHGDLHEFLvrhsphsdvgvssdDDGTASSLDQSDFLHIAIQIAAGMEYLSSHHYVHRDLAARNCLVGDG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 372 LCCKIADFGLARIIDSE--YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLE 449
Cdd:cd05048 161 LTVKISDFGLSRDIYSSdyYRVQSKSLLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIEMIR 240
                       250       260       270
                ....*....|....*....|....*....|....
gi 33469982 450 RGYRMPRPDTCPPELYRGVIaECWRSRPEERPTF 483
Cdd:cd05048 241 SRQLLPCPEDCPARVYSLMV-ECWHEIPSRRPRF 273
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
241-491 2.38e-65

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: 213.01  E-value: 2.38e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNN-----MKVAIKTLKegTMSPEA----FLGEANVMKALQHERLVRLYAVVTKEP---I 308
Cdd:cd05038   6 LKFIKQLGEGHFGSVELCRYDPLgdntgEQVAVKSLQ--PSGEEQhmsdFKREIEILRTLDHEYIVKYKGVCESPGrrsL 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 YIVTEYMARGCLLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--D 386
Cdd:cd05038  84 RLIMEYLPSGSLRDYLQRHR-DQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLpeD 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SE-YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNP--------------EVIRNLERG 451
Cdd:cd05038 163 KEyYYVKEPGESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPSQSPPALFlrmigiaqgqmivtRLLELLKSG 242
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 33469982 452 YRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05038 243 ERLPRPPSCPDEVYD-LMKECWEYEPQDRPSFSDLILIID 281
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
235-486 1.31e-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: 211.43  E-value: 1.31e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWM-----------GYYKNNMK------VAIKTLKEGTMSP--EAFLGEANVMKALQHER 295
Cdd:cd05051   1 EFPREKLEFVEKLGEGQFGEVHLceanglsdltsDDFIGNDNkdepvlVAVKMLRPDASKNarEDFLKEVKIMSQLKDPN 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 296 LVRLYAVVTK-EPIYIVTEYMARGCLLDFLKTDE----------GSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAA 364
Cdd:cd05051  81 IVRLLGVCTRdEPLCMIVEYMENGDLNQFLQKHEaetqgasatnSKTLSYGTLLYMATQIASGMKYLESLNFVHRDLATR 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 365 NILVSEALCCKIADFGLAR-IIDSEYTAQEG-AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRV-PYPGMSN 441
Cdd:cd05051 161 NCLVGPNYTIKIADFGMSRnLYSGDYYRIEGrAVLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCKEqPYEHLTD 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982 442 PEVIRNLERGYR-------MPRPDTCPPELYRgVIAECWRSRPEERPTFEFL 486
Cdd:cd05051 241 EQVIENAGEFFRddgmevyLSRPPNCPKEIYE-LMLECWRRDEEDRPTFREI 291
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
235-490 2.99e-64

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: 209.39  E-value: 2.99e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYY----KNNMKVAIKTLKEGTMSPE--AFLGEANVMKALQHERLVRLYAVVTK-EP 307
Cdd:cd05064   1 ELDNKSIKIERILGTGRFGELCRGCLklpsKRELPVAIHTLRAGCSDKQrrGFLAEALTLGQFDHSNIVRLEGVITRgNT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS 387
Cdd:cd05064  81 MMIVTEYMSNGALDSFLRKHEG-QLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRRLQEDKS 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 E--YTAQEGaKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELY 465
Cdd:cd05064 160 EaiYTTMSG-KSPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLH 238
                       250       260
                ....*....|....*....|....*
gi 33469982 466 RgVIAECWRSRPEERPTFEFLQSVL 490
Cdd:cd05064 239 Q-LMLDCWQKERGERPRFSQIHSIL 262
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
235-484 5.60e-64

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: 209.24  E-value: 5.60e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYYKN------NMKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLYAVVTK- 305
Cdd:cd05049   1 HIKRDTIVLKRELGEGAFGKVFLGECYNlepeqdKMLVAVKTLKDASSPDarKDFEREAELLTNLQHENIVKFYGVCTEg 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 EPIYIVTEYMARGCLLDFLK-------------TDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEAL 372
Cdd:cd05049  81 DPLLMVFEYMEHGDLNKFLRshgpdaaflasedSAPG-ELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNL 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 373 CCKIADFGLAR-IIDSEYTAQEG-AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLER 450
Cdd:cd05049 160 VVKIGDFGMSRdIYSTDYYRVGGhTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIECITQ 239
                       250       260       270
                ....*....|....*....|....*....|....
gi 33469982 451 GYRMPRPDTCPPELYRgVIAECWRSRPEERPTFE 484
Cdd:cd05049 240 GRLLQRPRTCPSEVYA-VMLGCWKREPQQRLNIK 272
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
233-501 3.45e-63

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: 208.28  E-value: 3.45e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEV----WMGYYKNN----MKVAIKTLKEGTMSPEA--FLGEANVMKAL-QHERLVRLYA 301
Cdd:cd05099   6 KWEFPRDRLVLGKPLGEGCFGQVvraeAYGIDKSRpdqtVTVAVKMLKDNATDKDLadLISEMELMKLIgKHKNIINLLG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 302 VVTKE-PIYIVTEYMARGCLLDFLK---------TDEGSR-----LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANI 366
Cdd:cd05099  86 VCTQEgPLYVIVEYAAKGNLREFLRarrppgpdyTFDITKvpeeqLSFKDLVSCAYQVARGMEYLESRRCIHRDLAARNV 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 367 LVSEALCCKIADFGLARIID--SEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEV 444
Cdd:cd05099 166 LVTEDNVMKIADFGLARGVHdiDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIPVEEL 245
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 445 IRNLERGYRMPRPDTCPPELYrGVIAECWRSRPEERPTFEFLQSVLEDFYTATERQY 501
Cdd:cd05099 246 FKLLREGHRMDKPSNCTHELY-MLMRECWHAVPTQRPTFKQLVEALDKVLAAVSEEY 301
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
234-494 8.93e-63

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: 206.36  E-value: 8.93e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMK------VAIKTLKEGTMSPE--AFLGEANVMKALQHERLVRLYAVVTK 305
Cdd:cd05061   1 WEVSREKITLLRELGQGSFGMVYEGNARDIIKgeaetrVAVKTVNESASLREriEFLNEASVMKGFTCHHVVRLLGVVSK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 -EPIYIVTEYMARGCLLDFLKT-------DEGSRL-SLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKI 376
Cdd:cd05061  81 gQPTLVVMELMAHGDLKSYLRSlrpeaenNPGRPPpTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 377 ADFGLARIIDSEYTAQEGAK--FPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRM 454
Cdd:cd05061 161 GDFGMTRDIYETDYYRKGGKglLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYL 240
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 33469982 455 PRPDTCPPELYrGVIAECWRSRPEERPTF-EFLQSVLEDFY 494
Cdd:cd05061 241 DQPDNCPERVT-DLMRMCWQFNPKMRPTFlEIVNLLKDDLH 280
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
233-492 6.23e-62

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: 204.65  E-value: 6.23e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEVW----MGYYKNNM--KVAIKTLKEGTMSPE--AFLGEANVMKAL-QHERLVRLYAVV 303
Cdd:cd05054   1 KWEFPRDRLKLGKPLGRGAFGKVIqasaFGIDKSATcrTVAVKMLKEGATASEhkALMTELKILIHIgHHLNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 TKE--PIYIVTEYMARGCLLDFLKT---------DEGSR---------------LSLPRLIDMSAQIAEGMAYIERMNSI 357
Cdd:cd05054  81 TKPggPLMVIVEFCKFGNLSNYLRSkreefvpyrDKGARdveeeedddelykepLTLEDLICYSFQVARGMEFLASRKCI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 358 HRDLRAANILVSEALCCKIADFGLARII--DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVP 435
Cdd:cd05054 161 HRDLAARNILLSENNVVKICDFGLARDIykDPDYVRKGDARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASP 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 436 YPGMS-NPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd05054 241 YPGVQmDEEFCRRLKEGTRMRAPEYTTPEIYQ-IMLDCWHGEPKERPTFSELVEKLGD 297
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
236-491 2.24e-61

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: 202.50  E-value: 2.24e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYKN------NMKVAIKTLKEGTMSP-EAFLGEANVMKALQHERLVRLYAVVTK-EP 307
Cdd:cd05092   2 IKRRDIVLKWELGEGAFGKVFLAECHNllpeqdKMLVAVKALKEATESArQDFQREAELLTVLQHQHIVRFYGVCTEgEP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKT--------DEGS-----RLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCC 374
Cdd:cd05092  82 LIMVFEYMRHGDLNRFLRShgpdakilDGGEgqapgQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVV 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 375 KIADFGLARIIDSEYTAQEGAK--FPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGY 452
Cdd:cd05092 162 KIGDFGMSRDIYSTDYYRVGGRtmLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQGR 241
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 33469982 453 RMPRPDTCPPELYrGVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05092 242 ELERPRTCPPEVY-AIMQGCWQREPQQRHSIKDIHSRLQ 279
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
240-491 5.62e-60

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: 199.42  E-value: 5.62e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWMGY------YKNNMKVAIKTLKEGTMSPE--AFLGEANVMKALQHERLVRLYAVVTK-EPIYI 310
Cdd:cd05045   1 NLVLGKTLGEGEFGKVVKATafrlkgRAGYTTVAVKMLKENASSSElrDLLSEFNLLKQVNHPHVIKLYGACSQdGPLLL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLK----------TDEGSR------------LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV 368
Cdd:cd05045  81 IVEYAKYGSLRSFLResrkvgpsylGSDGNRnssyldnpderaLTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 369 SEALCCKIADFGLARII--DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIR 446
Cdd:cd05045 161 AEGRKMKISDFGLSRDVyeEDSYVKRSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFN 240
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 33469982 447 NLERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05045 241 LLKTGYRMERPENCSEEMYN-LMLTCWKQEPDKRPTFADISKELE 284
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
246-494 1.54e-59

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: 197.11  E-value: 1.54e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKnnMK-----VAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMAR 317
Cdd:cd05116   2 ELGSGNFGTVKKGYYQ--MKkvvktVAVKILKNEANDPalkDELLREANVMQQLDNPYIVRMIGICEAESWMLVMEMAEL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE---YTAQEG 394
Cdd:cd05116  80 GPLNKFLQKNR--HVTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADenyYKAQTH 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYrGVIAECWR 474
Cdd:cd05116 158 GKWPVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMY-DLMKLCWT 236
                       250       260
                ....*....|....*....|
gi 33469982 475 SRPEERPTFEFLQSVLEDFY 494
Cdd:cd05116 237 YDVDERPGFAAVELRLRNYY 256
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
246-494 6.38e-59

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: 195.94  E-value: 6.38e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMK---VAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARGCL 320
Cdd:cd05115  11 ELGSGNFGCVKKGVYKMRKKqidVAIKVLKQGNEKAvrDEMMREAQIMHQLDNPYIVRMIGVCEAEALMLVMEMASGGPL 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFL--KTDEgsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII---DSEYTAQEGA 395
Cdd:cd05115  91 NKFLsgKKDE---ITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALgadDSYYKARSAG 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRS 475
Cdd:cd05115 168 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYA-LMSDCWIY 246
                       250
                ....*....|....*....
gi 33469982 476 RPEERPTFEFLQSVLEDFY 494
Cdd:cd05115 247 KWEDRPNFLTVEQRMRTYY 265
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
220-491 1.02e-57

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: 195.83  E-value: 1.02e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 220 CVRPApQNPWaQDEWEIPRQSLRLVRKLGSGQFGEV------WMGYYKNNMKVAIKTLKEGTMSPE--AFLGEANVMKAL 291
Cdd:cd05106  21 FIDPT-QLPY-NEKWEFPRDNLQFGKTLGAGAFGKVveatafGLGKEDNVLRVAVKMLKASAHTDEreALMSELKILSHL 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 292 -QHERLVRLYAVVTKE-PIYIVTEYMARGCLLDFL--------------------------------------------- 324
Cdd:cd05106  99 gQHKNIVNLLGACTHGgPVLVITEYCCYGDLLNFLrkkaetflnfvmalpeisetssdyknitlekkyirsdsgfssqgs 178
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 325 ----------------------KTDEGSR-LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGL 381
Cdd:cd05106 179 dtyvemrpvsssssqssdskdeEDTEDSWpLDLDDLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGL 258
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 382 ARII--DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMS-NPEVIRNLERGYRMPRPD 458
Cdd:cd05106 259 ARDImnDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILvNSKFYKMVKRGYQMSRPD 338
                       330       340       350
                ....*....|....*....|....*....|...
gi 33469982 459 TCPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05106 339 FAPPEIYS-IMKMCWNLEPTERPTFSQISQLIQ 370
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
241-486 9.84e-57

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: 190.24  E-value: 9.84e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYY---KNNMK--VAIKTLKEGTmSPEA---FLGEANVMKALQHERLVRLYAVVTKEPIYIVT 312
Cdd:cd05109   9 LKKVKVLGSGAFGTVYKGIWipdGENVKipVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVCRLLGICLTSTVQLVT 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID---SEY 389
Cdd:cd05109  88 QLMPYGCLLDYVRENKD-RIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDideTEY 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAqEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVI 469
Cdd:cd05109 167 HA-DGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYM-IM 244
                       250
                ....*....|....*..
gi 33469982 470 AECWRSRPEERPTFEFL 486
Cdd:cd05109 245 VKCWMIDSECRPRFREL 261
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
235-491 1.03e-56

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: 190.43  E-value: 1.03e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGY------YKNNMKVAIKTLKEGT---MSPEaFLGEANVMKALQHERLVRLYAV-VT 304
Cdd:cd05050   1 EYPRNNIEYVRDIGQGAFGRVFQARapgllpYEPFTMVAVKMLKEEAsadMQAD-FQREAALMAEFDHPNIVKLLGVcAV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 305 KEPIYIVTEYMARGCLLDFLK--------------------TDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAA 364
Cdd:cd05050  80 GKPMCLLFEYMAYGDLNEFLRhrspraqcslshstssarkcGLNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLATR 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 365 NILVSEALCCKIADFGLARIIDSE--YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNP 442
Cdd:cd05050 160 NCLVGENMVVKIADFGLSRNIYSAdyYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHE 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 33469982 443 EVIRNLERGYRMPRPDTCPPELYrGVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05050 240 EVIYYVRDGNVLSCPDNCPLELY-NLMRLCWSKLPSDRPSFASINRILQ 287
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
225-500 1.03e-56

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: 190.99  E-value: 1.03e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 225 PQNPwaqdEWEIPRQSLRLVRKLGSGQFGEVWM----GYYKNN----MKVAIKTLKEGTMSPEA--FLGEANVMKAL-QH 293
Cdd:cd05098   3 PEDP----RWELPRDRLVLGKPLGEGCFGQVVLaeaiGLDKDKpnrvTKVAVKMLKSDATEKDLsdLISEMEMMKMIgKH 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 294 ERLVRLYAVVTKE-PIYIVTEYMARGCLLDFLKTDE--------------GSRLSLPRLIDMSAQIAEGMAYIERMNSIH 358
Cdd:cd05098  79 KNIINLLGACTQDgPLYVIVEYASKGNLREYLQARRppgmeycynpshnpEEQLSSKDLVSCAYQVARGMEYLASKKCIH 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 359 RDLRAANILVSEALCCKIADFGLARIID--SEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPY 436
Cdd:cd05098 159 RDLAARNVLVTEDNVMKIADFGLARDIHhiDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPY 238
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33469982 437 PGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLEDFYTATERQ 500
Cdd:cd05098 239 PGVPVEELFKLLKEGHRMDKPSNCTNELYM-MMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQ 301
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
242-484 4.44e-56

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 187.74  E-value: 4.44e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    242 RLVRKLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMS--PEAFLGEANVMKALQHERLVRLYAV-VTKEPIYIVTEYMAR 317
Cdd:smart00220   2 EILEKLGEGSFGKVYLARDKKtGKLVAIKVIKKKKIKkdRERILREIKILKKLKHPNIVRLYDVfEDEDKLYLVMEYCEG 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    318 GCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE--GA 395
Cdd:smart00220  82 GDLFDLLK--KRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGEKLTTfvGT 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    396 KFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVI-RNLERGYR--MPRPDTCPPELyRGVIAEC 472
Cdd:smart00220 160 PE---YMAPEVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDDQLLELfKKIGKPKPpfPPPEWDISPEA-KDLIRKL 234
                          250
                   ....*....|..
gi 33469982    473 WRSRPEERPTFE 484
Cdd:smart00220 235 LVKDPEKRLTAE 246
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
244-486 2.63e-55

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: 187.54  E-value: 2.63e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYY-----KNNMKVAIKTLKEGTmSPEA---FLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYM 315
Cdd:cd05108  12 IKVLGSGAFGTVYKGLWipegeKVKIPVAIKELREAT-SPKAnkeILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLM 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII---DSEYTAq 392
Cdd:cd05108  91 PFGCLLDYVREHK-DNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLgaeEKEYHA- 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAEC 472
Cdd:cd05108 169 EGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYM-IMVKC 247
                       250
                ....*....|....
gi 33469982 473 WRSRPEERPTFEFL 486
Cdd:cd05108 248 WMIDADSRPKFREL 261
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
225-500 3.98e-55

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: 187.14  E-value: 3.98e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 225 PQNPwaqdEWEIPRQSLRLVRKLGSGQFGEVWMGYY--------KNNMKVAIKTLKEGTMSPEA--FLGEANVMKAL-QH 293
Cdd:cd05101  14 PEDP----KWEFPRDKLTLGKPLGEGCFGQVVMAEAvgidkdkpKEAVTVAVKMLKDDATEKDLsdLVSEMEMMKMIgKH 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 294 ERLVRLYAVVTKE-PIYIVTEYMARGCLLDFLK----------------TDEgsRLSLPRLIDMSAQIAEGMAYIERMNS 356
Cdd:cd05101  90 KNIINLLGACTQDgPLYVIVEYASKGNLREYLRarrppgmeysydinrvPEE--QMTFKDLVSCTYQLARGMEYLASQKC 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 357 IHRDLRAANILVSEALCCKIADFGLARIIDS--EYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRV 434
Cdd:cd05101 168 IHRDLAARNVLVTENNVMKIADFGLARDINNidYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGS 247
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 435 PYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLEDFYTATERQ 500
Cdd:cd05101 248 PYPGIPVEELFKLLKEGHRMDKPANCTNELYM-MMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNE 312
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
236-492 4.18e-55

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: 185.75  E-value: 4.18e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYKNNMK------VAIKTLKE--GTMSPEAFLGEANVMKALQHERLVRLYAVV-TKE 306
Cdd:cd05046   2 FPRSNLQEITTLGRGEFGEVFLAKAKGIEEeggetlVLVKALQKtkDENLQSEFRRELDMFRKLSHKNVVRLLGLCrEAE 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 PIYIVTEYMARGCLLDFLKTDEGSR-------LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADF 379
Cdd:cd05046  82 PHYMILEYTDLGDLKQFLRATKSKDeklkpppLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLL 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 380 GLAR-IIDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERG-YRMPRP 457
Cdd:cd05046 162 SLSKdVYNSEYYKLRNALIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLQAGkLELPVP 241
                       250       260       270
                ....*....|....*....|....*....|....*
gi 33469982 458 DTCPPELYRgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd05046 242 EGCPSRLYK-LMTRCWAVNPKDRPSFSELVSALGE 275
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
120-219 8.85e-55

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: 178.93  E-value: 8.85e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVT-TQGELIKHYKIRCLDEGGYYISPRITFPSL 198
Cdd:cd09933   1 EAEEWFFGKIKRKDAEKLLLAPGNPRGTFLIRESETTPGAYSLSVRDGDdARGDTVKHYRIRKLDNGGYYITTRATFPTL 80
                        90       100
                ....*....|....*....|.
gi 33469982 199 QALVQHYSKKGDGLCQRLTLP 219
Cdd:cd09933  81 QELVQHYSKDADGLCCRLTVP 101
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
234-491 9.15e-55

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: 185.24  E-value: 9.15e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMK------VAIKTLKEGTMSPE--AFLGEANVMKALQHERLVRLYAVVTK 305
Cdd:cd05062   1 WEVAREKITMSRELGQGSFGMVYEGIAKGVVKdepetrVAIKTVNEAASMREriEFLNEASVMKEFNCHHVVRLLGVVSQ 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 -EPIYIVTEYMARGCLLDFL-----KTDEGSRLSLP---RLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKI 376
Cdd:cd05062  81 gQPTLVIMELMTRGDLKSYLrslrpEMENNPVQAPPslkKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 377 ADFGLARIIDSEYTAQEGAK--FPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRM 454
Cdd:cd05062 161 GDFGMTRDIYETDYYRKGGKglLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGLL 240
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 33469982 455 PRPDTCPPELYRgVIAECWRSRPEERPTF-EFLQSVLE 491
Cdd:cd05062 241 DKPDNCPDMLFE-LMRMCWQYNPKMRPSFlEIISSIKE 277
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
245-496 9.76e-55

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: 184.60  E-value: 9.76e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYY----KNNMKVAIKTLK--EGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE---PIyIVTEYM 315
Cdd:cd05058   1 EVIGKGHFGCVYHGTLidsdGQKIHCAVKSLNriTDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPSegsPL-VVLPYM 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR-IIDSEYTA--- 391
Cdd:cd05058  80 KHGDLRNFIR-SETHNPTVKDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARdIYDKEYYSvhn 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAE 471
Cdd:cd05058 159 HTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYE-VMLS 237
                       250       260
                ....*....|....*....|....*
gi 33469982 472 CWRSRPEERPTFEFLQSVLEDFYTA 496
Cdd:cd05058 238 CWHPKPEMRPTFSELVSRISQIFST 262
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
235-484 3.19e-54

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


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 184.06  E-value: 3.19e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGY-YKNNMK----VAIKTLKE--GTMSPEAFLGEANVMKALQHERLVRLYAVVTKE- 306
Cdd:cd05090   1 ELPLSAVRFMEELGECAFGKIYKGHlYLPGMDhaqlVAIKTLKDynNPQQWNEFQQEASLMTELHHPNIVCLLGVVTQEq 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 PIYIVTEYMARGCLLDFL-----------KTDEG----SRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA 371
Cdd:cd05090  81 PVCMLFEFMNQGDLHEFLimrsphsdvgcSSDEDgtvkSSLDHGDFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQ 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 372 LCCKIADFGLARIIDSE--YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLE 449
Cdd:cd05090 161 LHVKISDLGLSREIYSSdyYRVQNKSLLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVR 240
                       250       260       270
                ....*....|....*....|....*....|....*
gi 33469982 450 RGYRMPRPDTCPPELYrGVIAECWRSRPEERPTFE 484
Cdd:cd05090 241 KRQLLPCSEDCPPRMY-SLMTECWQEIPSRRPRFK 274
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
225-497 1.44e-53

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: 183.68  E-value: 1.44e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 225 PQNPwaqdEWEIPRQSLRLVRKLGSGQFGEVWM----GYYKNN----MKVAIKTLKEGTMSPEA--FLGEANVMKAL-QH 293
Cdd:cd05100   2 PADP----KWELSRTRLTLGKPLGEGCFGQVVMaeaiGIDKDKpnkpVTVAVKMLKDDATDKDLsdLVSEMEMMKMIgKH 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 294 ERLVRLYAVVTKE-PIYIVTEYMARGCLLDFLKTDE--------------GSRLSLPRLIDMSAQIAEGMAYIERMNSIH 358
Cdd:cd05100  78 KNIINLLGACTQDgPLYVLVEYASKGNLREYLRARRppgmdysfdtcklpEEQLTFKDLVSCAYQVARGMEYLASQKCIH 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 359 RDLRAANILVSEALCCKIADFGLARIIDS--EYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPY 436
Cdd:cd05100 158 RDLAARNVLVTEDNVMKIADFGLARDVHNidYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPY 237
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 437 PGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLEDFYTAT 497
Cdd:cd05100 238 PGIPVEELFKLLKEGHRMDKPANCTHELYM-IMRECWHAVPSQRPTFKQLVEDLDRVLTVT 297
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
235-490 2.57e-53

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: 181.37  E-value: 2.57e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYY------KNNMKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLYAVVTKE 306
Cdd:cd05091   2 EINLSAVRFMEELGEDRFGKVYKGHLfgtapgEQTQAVAIKTLKDKAEGPlrEEFRHEAMLRSRLQHPNIVCLLGVVTKE 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 -PIYIVTEYMARGCLLDFL----------KTDEG----SRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA 371
Cdd:cd05091  82 qPMSMIFSYCSHGDLHEFLvmrsphsdvgSTDDDktvkSTLEPADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFDK 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 372 LCCKIADFGLAR-IIDSEYTAQEGAK-FPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLE 449
Cdd:cd05091 162 LNVKISDLGLFReVYAADYYKLMGNSlLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVIEMIR 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 33469982 450 RGYRMPRPDTCPPELYrGVIAECWRSRPEERPTFEFLQSVL 490
Cdd:cd05091 242 NRQVLPCPDDCPAWVY-TLMLECWNEFPSRRPRFKDIHSRL 281
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
247-483 5.22e-53

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: 180.24  E-value: 5.22e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK---NNMKVAIKTLKEGTMSPEA--FLGEANVMKAL-QHERLVRLY-AVVTKEPIYIVTEYMARGC 319
Cdd:cd05047   3 IGEGNFGQVLKARIKkdgLRMDAAIKRMKEYASKDDHrdFAGELEVLCKLgHHPNIINLLgACEHRGYLYLAIEYAPHGN 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLK------TD--------EGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIi 385
Cdd:cd05047  83 LLDFLRksrvleTDpafaiansTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELY 465
Cdd:cd05047 162 QEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVY 241
                       250
                ....*....|....*...
gi 33469982 466 RgVIAECWRSRPEERPTF 483
Cdd:cd05047 242 D-LMRQCWREKPYERPSF 258
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
233-493 1.28e-52

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: 181.33  E-value: 1.28e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEV----WMGYYKNNM--KVAIKTLKEGTMSPE--AFLGEANVMKAL-QHERLVRLYAVV 303
Cdd:cd05102   1 QWEFPRDRLRLGKVLGHGAFGKVveasAFGIDKSSSceTVAVKMLKEGATASEhkALMSELKILIHIgNHLNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 TKE--PIYIVTEYMARGCLLDFLKT------------------------------------DEGSR-------------- 331
Cdd:cd05102  81 TKPngPLMVIVEFCKYGNLSNFLRAkregfspyrersprtrsqvrsmveavradrrsrqgsDRVASftestsstnqprqe 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 332 --------LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEYTAQEGAKFPIKW 401
Cdd:cd05102 161 vddlwqspLTMEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIykDPDYVRKGSARLPLKW 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 402 TAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMS-NPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSRPEER 480
Cdd:cd05102 241 MAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQiNEEFCQRLKDGTRMRAPEYATPEIYR-IMLSCWHGDPKER 319
                       330
                ....*....|...
gi 33469982 481 PTFEFLQSVLEDF 493
Cdd:cd05102 320 PTFSDLVEILGDL 332
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
241-488 6.25e-52

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: 178.34  E-value: 6.25e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYY-----KNNMKVAIKTLKEgTMSPEA---FLGEANVMKALQHERLVRLYAVVTKEPIYIVT 312
Cdd:cd05110   9 LKRVKVLGSGAFGTVYKGIWvpegeTVKIPVAIKILNE-TTGPKAnveFMDEALIMASMDHPHLVRLLGVCLSPTIQLVT 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFL---KTDEGSRLslprLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID--- 386
Cdd:cd05110  88 QLMPHGCLLDYVhehKDNIGSQL----LLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEgde 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SEYTAqEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYR 466
Cdd:cd05110 164 KEYNA-DGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYM 242
                       250       260
                ....*....|....*....|..
gi 33469982 467 gVIAECWRSRPEERPTFEFLQS 488
Cdd:cd05110 243 -VMVKCWMIDADSRPKFKELAA 263
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
234-495 1.23e-51

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: 180.59  E-value: 1.23e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEV------WMGYYKNNMKVAIKTLKEGTMSPE--AFLGEANVMKAL-QHERLVRLYAVVT 304
Cdd:cd05107  32 WEMPRDNLVLGRTLGSGAFGRVveatahGLSHSQSTMKVAVKMLKSTARSSEkqALMSELKIMSHLgPHLNIVNLLGACT 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 305 KE-PIYIVTEYMARGCLLDFL--------------KTDEGSRLS------LPR--------------------------- 336
Cdd:cd05107 112 KGgPIYIITEYCRYGDLVDYLhrnkhtflqyyldkNRDDGSLISggstplSQRkshvslgsesdggymdmskdesadyvp 191
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 337 -------------------------------------------------LIDMSAQIAEGMAYIERMNSIHRDLRAANIL 367
Cdd:cd05107 192 mqdmkgtvkyadiessnyespydqylpsapertrrdtlinespalsymdLVGFSYQVANGMEFLASKNCVHRDLAARNVL 271
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 368 VSEALCCKIADFGLARII--DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVI 445
Cdd:cd05107 272 ICEGKLVKICDFGLARDImrDSNYISKGSTFLPLKWMAPESIFNNLYTTLSDVWSFGILLWEIFTLGGTPYPELPMNEQF 351
                       330       340       350       360       370
                ....*....|....*....|....*....|....*....|....*....|.
gi 33469982 446 RN-LERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLEDFYT 495
Cdd:cd05107 352 YNaIKRGYRMAKPAHASDEIYE-IMQKCWEEKFEIRPDFSQLVHLVGDLLT 401
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
242-482 2.19e-51

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: 175.47  E-value: 2.19e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMSPEA----FLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYM 315
Cdd:cd14014   3 RLVRLLGRGGMGEVYRARDTLlGRPVAIKVLRPELAEDEEfrerFLREARALARLSHPNIVRVYDVGeDDGRPYIVMEYV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGA 395
Cdd:cd14014  83 EGGSLADLLR--ERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGS 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KF--PIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMP---RPDTCPPELYRgVIA 470
Cdd:cd14014 161 VLgtPA-YMAPEQARGGPVDPRSDIYSLGVVLYELLT-GRPPFDGDSPAAVLAKHLQEAPPPpspLNPDVPPALDA-IIL 237
                       250
                ....*....|..
gi 33469982 471 ECWRSRPEERPT 482
Cdd:cd14014 238 RALAKDPEERPQ 249
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
233-497 2.29e-51

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: 178.25  E-value: 2.29e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEVW----MGYYKNNM--KVAIKTLKEGTMSPE--AFLGEANVMKALQHE-RLVRLYAVV 303
Cdd:cd05103   1 KWEFPRDRLKLGKPLGRGAFGQVIeadaFGIDKTATcrTVAVKMLKEGATHSEhrALMSELKILIHIGHHlNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 TKE--PIYIVTEYMARGCLLDFLKT------------------------------------------------------- 326
Cdd:cd05103  81 TKPggPLMVIVEFCKFGNLSAYLRSkrsefvpyktkgarfrqgkdyvgdisvdlkrrldsitssqssassgfveekslsd 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 327 ----DEGSR------LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEYTAQEG 394
Cdd:cd05103 161 veeeEAGQEdlykdfLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIykDPDYVRKGD 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMS-NPEVIRNLERGYRMPRPDTCPPELYRGVIaECW 473
Cdd:cd05103 241 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTML-DCW 319
                       330       340
                ....*....|....*....|....
gi 33469982 474 RSRPEERPTFEFLQSVLEDFYTAT 497
Cdd:cd05103 320 HGEPSQRPTFSELVEHLGNLLQAN 343
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
247-483 6.57e-51

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: 175.57  E-value: 6.57e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK---NNMKVAIKTLKEGTMSPEA--FLGEANVMKAL-QHERLVRLY-AVVTKEPIYIVTEYMARGC 319
Cdd:cd05089  10 IGEGNFGQVIKAMIKkdgLKMNAAIKMLKEFASENDHrdFAGELEVLCKLgHHPNIINLLgACENRGYLYIAIEYAPYGN 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLK------TD--------EGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIi 385
Cdd:cd05089  90 LLDFLRksrvleTDpafakehgTASTLTSQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIADFGLSRG- 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELY 465
Cdd:cd05089 169 EEVYVKKTMGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEKPRNCDDEVY 248
                       250
                ....*....|....*...
gi 33469982 466 RgVIAECWRSRPEERPTF 483
Cdd:cd05089 249 E-LMRQCWRDRPYERPPF 265
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
239-488 7.31e-51

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: 174.76  E-value: 7.31e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYY---KNNMK--VAIKTL--KEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIV 311
Cdd:cd05111   7 TELRKLKVLGSGVFGTVHKGIWipeGDSIKipVAIKVIqdRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGICPGASLQLV 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII---DSE 388
Cdd:cd05111  87 TQLLPLGSLLDHVRQHRGS-LGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLypdDKK 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEgAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgV 468
Cdd:cd05111 166 YFYSE-AKTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQICTIDVYM-V 243
                       250       260
                ....*....|....*....|
gi 33469982 469 IAECWRSRPEERPTFEFLQS 488
Cdd:cd05111 244 MVKCWMIDENIRPTFKELAN 263
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
241-492 1.23e-50

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: 174.26  E-value: 1.23e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNN----MKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAV------VTKEP 307
Cdd:cd05035   1 LKLGKILGEGEFGSVMEAQLKQDdgsqLKVAVKTMKVDIHTYseiEEFLSEAACMKDFDHPNVMRLIGVcftasdLNKPP 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 I-YIVTEYMARGCLLDFL---KTDEGS-RLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd05035  81 SpMVILPFMKHGDLHSYLlysRLGGLPeKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLS 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSEYTAQEG--AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTC 460
Cdd:cd05035 161 RKIYSGDYYRQGriSKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPEDC 240
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 461 PPELYRgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd05035 241 LDEVYF-LMYFCWTVDPKDRPTFTKLREVLEN 271
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
234-491 1.47e-50

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: 177.52  E-value: 1.47e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGY------YKNNMKVAIKTLKEGTMSPE--AFLGEANVMKAL-QHERLVRLYAVVT 304
Cdd:cd05105  32 WEFPRDGLVLGRILGSGAFGKVVEGTayglsrSQPVMKVAVKMLKPTARSSEkqALMSELKIMTHLgPHLNIVNLLGACT 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 305 KE-PIYIVTEYMARGCLLDFLK-------------------------TDEGSR--------------------------- 331
Cdd:cd05105 112 KSgPIYIITEYCFYGDLVNYLHknrdnflsrhpekpkkdldifginpADESTRsyvilsfenkgdymdmkqadttqyvpm 191
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 332 ------------------------------------------LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVS 369
Cdd:cd05105 192 leikeaskysdiqrsnydrpasykgsndsevknllsddgsegLTTLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLA 271
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 370 EALCCKIADFGLARII--DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRN 447
Cdd:cd05105 272 QGKIVKICDFGLARDImhDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMIVDSTFYN 351
                       330       340       350       360
                ....*....|....*....|....*....|....*....|....*
gi 33469982 448 -LERGYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05105 352 kIKSGYRMAKPDHATQEVYD-IMVKCWNSEPEKRPSFLHLSDIVE 395
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
235-492 3.59e-50

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: 173.64  E-value: 3.59e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWM----GYYKNNMK-------------VAIKTLKE--GTMSPEAFLGEANVMKALQHER 295
Cdd:cd05095   1 EFPRKLLTFKEKLGEGQFGEVHLceaeGMEKFMDKdfalevsenqpvlVAVKMLRAdaNKNARNDFLKEIKIMSRLKDPN 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 296 LVRLYAV-VTKEPIYIVTEYMARGCLLDFLKTDE----------GSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAA 364
Cdd:cd05095  81 IIRLLAVcITDDPLCMITEYMENGDLNQFLSRQQpegqlalpsnALTVSYSDLRFMAAQIASGMKYLSSLNFVHRDLATR 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 365 NILVSEALCCKIADFGLARIIDS--EYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGR-VPYPGMSN 441
Cdd:cd05095 161 NCLVGKNYTIKIADFGMSRNLYSgdYYRIQGRAVLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFCReQPYSQLSD 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 442 PEVIRNLERGYR-------MPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd05095 241 EQVIENTGEFFRdqgrqtyLPQPALCPDSVYK-LMLSCWRRDTKDRPSFQEIHTLLQE 297
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
236-491 5.33e-50

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: 172.79  E-value: 5.33e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYKNN----MKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVVTKE-- 306
Cdd:cd05074   6 IQEQQFTLGRMLGKGEFGSVREAQLKSEdgsfQKVAVKMLKADIFSSsdiEEFLREAACMKEFDHPNVIKLIGVSLRSra 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 ----PI-YIVTEYMARGCLLDFLKT----DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIA 377
Cdd:cd05074  86 kgrlPIpMVILPFMKHGDLHTFLLMsrigEEPFTLPLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVA 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 378 DFGLARIIDS-EYTAQEGA-KFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMP 455
Cdd:cd05074 166 DFGLSKKIYSgDYYRQGCAsKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGNRLK 245
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 33469982 456 RPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05074 246 QPPDCLEDVYE-LMCQCWSPEPKCRPSFQHLRDQLE 280
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
241-491 6.20e-50

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: 172.50  E-value: 6.20e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNN---MKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVVTK--------E 306
Cdd:cd05075   2 LALGKTLGEGEFGSVMEGQLNQDdsvLKVAVKTMKIAICTRsemEDFLSEAVCMKEFDHPNVMRLIGVCLQntesegypS 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 PIYIVTeYMARGCLLDFLKTdegSRLS-----LPR--LIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADF 379
Cdd:cd05075  82 PVVILP-FMKHGDLHSFLLY---SRLGdcpvyLPTqmLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADF 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 380 GLAR-IIDSEYTAQ-EGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRP 457
Cdd:cd05075 158 GLSKkIYNGDYYRQgRISKMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQP 237
                       250       260       270
                ....*....|....*....|....*....|....
gi 33469982 458 DTCPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05075 238 PDCLDGLYE-LMSSCWLLNPKDRPSFETLRCELE 270
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
236-491 6.99e-50

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: 172.43  E-value: 6.99e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYK----NNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVVTK--- 305
Cdd:cd14204   4 IDRNLLSLGKVLGEGEFGSVMEGELQqpdgTNHKVAVKTMKLDNFSQreiEEFLSEAACMKDFNHPNVIRLLGVCLEvgs 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 ----EPIyIVTEYMARGCLLDFL---KTDEGSR-LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIA 377
Cdd:cd14204  84 qripKPM-VILPFMKYGDLHSFLlrsRLGSGPQhVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 378 DFGLARIIDSEYTAQEG--AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMP 455
Cdd:cd14204 163 DFGLSKKIYSGDYYRQGriAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHRLK 242
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 33469982 456 RPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14204 243 QPEDCLDELYD-IMYSCWRSDPTDRPTFTQLRENLE 277
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
236-497 1.28e-49

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: 171.76  E-value: 1.28e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYKN------NMKVAIKTLKEGTMSPEA-FLGEANVMKALQHERLVRLYAV-VTKEP 307
Cdd:cd05093   2 IKRHNIVLKRELGEGAFGKVFLAECYNlcpeqdKILVAVKTLKDASDNARKdFHREAELLTNLQHEHIVKFYGVcVEGDP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKT-----------DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKI 376
Cdd:cd05093  82 LIMVFEYMKHGDLNKFLRAhgpdavlmaegNRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKI 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 377 ADFGLARIIDSE--YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRM 454
Cdd:cd05093 162 GDFGMSRDVYSTdyYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVL 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 33469982 455 PRPDTCPPELYRGVIAeCWRSRPEERPTFEFLQSVLEDFYTAT 497
Cdd:cd05093 242 QRPRTCPKEVYDLMLG-CWQREPHMRLNIKEIHSLLQNLAKAS 283
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
247-484 2.13e-49

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: 168.99  E-value: 2.13e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-VAIKTLK--EGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCLLD 322
Cdd:cd00180   1 LGKGSFGKVYKARDKETGKkVAVKVIPkeKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENfLYLVMEYCEGGSLKD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE--YTAQEGAKFPIK 400
Cdd:cd00180  81 LLKENKG-PLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDdsLLKTTGGTTPPY 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 WTAPEAIHFGVFTIKADVWSFGVLLMEVvtygrvpypgmsnpEVIRNLergyrmprpdtcppelyrgvIAECWRSRPEER 480
Cdd:cd00180 160 YAPPELLGGRYYGPKVDIWSLGVILYEL--------------EELKDL--------------------IRRMLQYDPKKR 205

                ....
gi 33469982 481 PTFE 484
Cdd:cd00180 206 PSAK 209
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
120-221 2.43e-49

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: 164.75  E-value: 2.43e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQ-GELIKHYKIRCLDEGGYYISPRITFPSL 198
Cdd:cd10363   1 ETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPQhGDTVKHYKIRTLDNGGFYISPRSTFSTL 80
                        90       100
                ....*....|....*....|...
gi 33469982 199 QALVQHYSKKGDGLCQRLTLPCV 221
Cdd:cd10363  81 QELVDHYKKGNDGLCQKLSVPCM 103
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
236-497 2.52e-49

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: 170.96  E-value: 2.52e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGY------YKNNMKVAIKTLKEGTMSPEA-FLGEANVMKALQHERLVRLYAV-VTKEP 307
Cdd:cd05094   2 IKRRDIVLKRELGEGAFGKVFLAEcynlspTKDKMLVAVKTLKDPTLAARKdFQREAELLTNLQHDHIVKFYGVcGDGDP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKT--------------DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC 373
Cdd:cd05094  82 LIMVFEYMKHGDLNKFLRAhgpdamilvdgqprQAKGELGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLL 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 374 CKIADFGLAR-IIDSEYTAQEG-AKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERG 451
Cdd:cd05094 162 VKIGDFGMSRdVYSTDYYRVGGhTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECITQG 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 33469982 452 YRMPRPDTCPPELYrGVIAECWRSRPEERPTFEFLQSVLEDFYTAT 497
Cdd:cd05094 242 RVLERPRVCPKEVY-DIMLGCWQREPQQRLNIKEIYKILHALGKAT 286
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
120-219 5.03e-49

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: 164.00  E-value: 5.03e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQ-GELIKHYKIRCLDEGGYYISPRITFPSL 198
Cdd:cd10364   1 ETEEWFFKDITRKDAERQLLAPGNSAGAFLIRESETLKGSYSLSVRDYDPQhGDVIKHYKIRSLDNGGYYISPRITFPCI 80
                        90       100
                ....*....|....*....|.
gi 33469982 199 QALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10364  81 SDMIKHYQKQSDGLCRRLEKA 101
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
233-493 8.05e-49

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: 171.34  E-value: 8.05e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEV----WMGYYKNNM--KVAIKTLKEGTMSPE--AFLGEANVMKALQHE-RLVRLYAVV 303
Cdd:cd14207   1 KWEFARERLKLGKSLGRGAFGKVvqasAFGIKKSPTcrVVAVKMLKEGATASEykALMTELKILIHIGHHlNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 TKE--PIYIVTEYMARGCLLDFLKTD-------------------------EGSR------------------------- 331
Cdd:cd14207  81 TKSggPLMVIVEYCKYGNLSNYLKSKrdffvtnkdtslqeelikekkeaepTGGKkkrlesvtssesfassgfqedksls 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 332 ----------------LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEYTAQE 393
Cdd:cd14207 161 dveeeeedsgdfykrpLTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIykNPDYVRKG 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMS-NPEVIRNLERGYRMPRPDTCPPELYRgVIAEC 472
Cdd:cd14207 241 DARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQiDEDFCSKLKEGIRMRAPEFATSEIYQ-IMLDC 319
                       330       340
                ....*....|....*....|.
gi 33469982 473 WRSRPEERPTFEFLQSVLEDF 493
Cdd:cd14207 320 WQGDPNERPRFSELVERLGDL 340
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
235-490 8.06e-48

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: 167.46  E-value: 8.06e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEV----------WMGYYKNNMK-----VAIKTLKEGTMSP--EAFLGEANVMKALQHERLV 297
Cdd:cd05097   1 EFPRQQLRLKEKLGEGQFGEVhlceaeglaeFLGEGAPEFDgqpvlVAVKMLRADVTKTarNDFLKEIKIMSRLKNPNII 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 298 RLYAV-VTKEPIYIVTEYMARGCLLDFL----------KTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANI 366
Cdd:cd05097  81 RLLGVcVSDDPLCMITEYMENGDLNQFLsqreiestftHANNIPSVSIANLLYMAVQIASGMKYLASLNFVHRDLATRNC 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 367 LVSEALCCKIADFGLARIIDSE--YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGR-VPYPGMSNPE 443
Cdd:cd05097 161 LVGNHYTIKIADFGMSRNLYSGdyYRIQGRAVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLCKeQPYSLLSDEQ 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 33469982 444 VIRNLERGYR-------MPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVL 490
Cdd:cd05097 241 VIENTGEFFRnqgrqiyLSQTPLCPSPVFK-LMMRCWSRDIKDRPTFNKIHHFL 293
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
233-491 9.34e-48

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: 169.31  E-value: 9.34e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEV----WMGYYKNN--MKVAIKTLKEGTMSPE--AFLGEANVMKAL-QHERLVRLYAVV 303
Cdd:cd05104  29 KWEFPRDRLRFGKTLGAGAFGKVveatAYGLAKADsaMTVAVKMLKPSAHSTEreALMSELKVLSYLgNHINIVNLLGAC 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 T-KEPIYIVTEYMARGCLLDFLK--------------------------------------------------------- 325
Cdd:cd05104 109 TvGGPTLVITEYCCYGDLLNFLRrkrdsficpkfedlaeaalyrnllhqremacdslneymdmkpsvsyvvptkadkrrg 188
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 326 ----------------TDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DS 387
Cdd:cd05104 189 vrsgsyvdqdvtseilEEDELALDTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIrnDS 268
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMS-NPEVIRNLERGYRMPRPDTCPPELYR 466
Cdd:cd05104 269 NYVVKGNARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPvDSKFYKMIKEGYRMDSPEFAPSEMYD 348
                       330       340
                ....*....|....*....|....*
gi 33469982 467 gVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05104 349 -IMRSCWDADPLKRPTFKQIVQLIE 372
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
236-496 2.12e-47

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


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 165.70  E-value: 2.12e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 236 IPRQSLRLVRKLGSGQFGEVWMGYYKNNM----KVAIKTLKEGTmSP---EAFLGEANVMKALQHERLVRLYAVVTK--E 306
Cdd:cd05043   3 VSRERVTLSDLLQEGTFGRIFHGILRDEKgkeeEVLVKTVKDHA-SEiqvTMLLQESSLLYGLSHQNLLPILHVCIEdgE 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 PIYIVTEYMARGCLLDFLK------TDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFG 380
Cdd:cd05043  82 KPMVLYPYMNWGNLKLFLQqcrlseANNPQALSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNA 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 381 LARII---------DSEYTaqegakfPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERG 451
Cdd:cd05043 162 LSRDLfpmdyhclgDNENR-------PIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDG 234
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 33469982 452 YRMPRPDTCPPELYrGVIAECWRSRPEERPTFEFLQSVLEDFYTA 496
Cdd:cd05043 235 YRLAQPINCPDELF-AVMACCWALDPEERPSFQQLVQCLTDFHAQ 278
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
241-492 2.45e-47

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: 165.57  E-value: 2.45e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYY---KNNMK--VAIKTLKEGTMSP-EAFLGEANVMKALQHERLVRLYAV---VTKEPIYIV 311
Cdd:cd14205   6 LKFLQQLGKGNFGSVEMCRYdplQDNTGevVAVKKLQHSTEEHlRDFEREIEILKSLQHDNIVKYKGVcysAGRRNLRLI 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEY 389
Cdd:cd14205  86 MEYLPYGSLRDYLQKHK-ERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLpqDKEY 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 -TAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTY---------------GRVPYPGMSNPEVIRNLERGYR 453
Cdd:cd14205 165 yKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYieksksppaefmrmiGNDKQGQMIVFHLIELLKNNGR 244
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 33469982 454 MPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd14205 245 LPRPDGCPDEIYM-IMTECWNNNVNQRPSFRDLALRVDQ 282
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
235-490 5.33e-47

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: 165.49  E-value: 5.33e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYYKN-----------NMK------VAIKTLKegtmsPEA-------FLGEANVMKA 290
Cdd:cd05096   1 KFPRGHLLFKEKLGEGQFGEVHLCEVVNpqdlptlqfpfNVRkgrpllVAVKILR-----PDAnknarndFLKEVKILSR 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 291 LQHERLVRLYAV-VTKEPIYIVTEYMARGCLLDFL-------KTDEGSR----------LSLPRLIDMSAQIAEGMAYIE 352
Cdd:cd05096  76 LKDPNIIRLLGVcVDEDPLCMITEYMENGDLNQFLsshhlddKEENGNDavppahclpaISYSSLLHVALQIASGMKYLS 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 353 RMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd05096 156 SLNFVHRDLATRNCLVGENLTIKIADFGMSRNLyaGDYYRIQGRAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEILM 235
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 431 YGRV-PYPGMSNPEVIRNLERGYR-------MPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVL 490
Cdd:cd05096 236 LCKEqPYGELTDEQVIENAGEFFRdqgrqvyLFRPPPCPQGLYE-LMLQCWSRDCRERPSFSDIHAFL 302
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
120-219 3.70e-46

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: 156.18  E-value: 3.70e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDV-TTQGELIKHYKIRCLDEGGYYISPRITFPSL 198
Cdd:cd10362   1 EPEPWFFKNLSRNDAERQLLAPGNTHGSFLIRESETTAGSFSLSVRDFdQNQGEVVKHYKIRNLDNGGFYISPRITFPGL 80
                        90       100
                ....*....|....*....|.
gi 33469982 199 QALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10362  81 HELVRHYTNASDGLCTRLSRP 101
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
242-482 5.26e-46

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: 161.15  E-value: 5.26e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPE---AFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTEYMA 316
Cdd:cd06606   3 KKGELLGKGSFGSVYLALNLDTGElMAVKEVELSGDSEEeleALEREIRILSSLKHPNIVRyLGTERTENTLNIFLEYVP 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTdeGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAK 396
Cdd:cd06606  83 GGSLASLLKK--FGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIATGEGTKS 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 397 F---PIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNP-----EVIRNLErgyrMPR-PDTCPPELyRG 467
Cdd:cd06606 161 LrgtPY-WMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPWSELGNPvaalfKIGSSGE----PPPiPEHLSEEA-KD 233
                       250
                ....*....|....*
gi 33469982 468 VIAECWRSRPEERPT 482
Cdd:cd06606 234 FLRKCLQRDPKKRPT 248
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
241-491 2.76e-44

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: 157.36  E-value: 2.76e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYY-----KNNMKVAIKTLKEGTMSP-EAFLGEANVMKALQHERLVRLYAVV---TKEPIYIV 311
Cdd:cd05081   6 LKYISQLGKGNFGSVELCRYdplgdNTGALVAVKQLQHSGPDQqRDFQREIQILKALHSDFIVKYRGVSygpGRRSLRLV 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSE- 388
Cdd:cd05081  86 MEYLPSGCLRDFLQRHR-ARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLplDKDy 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTY---GRVP---YPGMSNPE--------VIRNLERGYRM 454
Cdd:cd05081 165 YVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYcdkSCSPsaeFLRMMGCErdvpalcrLLELLEEGQRL 244
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 33469982 455 PRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd05081 245 PAPPACPAEVHE-LMKLCWAPSPQDRPSFSALGPQLD 280
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
238-494 5.56e-44

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: 156.60  E-value: 5.56e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 238 RQSLRLVRKLGSGQFGEVWMGYYKNNMK-----VAIKTLKE--GTMSPEAFLGEANVMKALQHERLVRLYAVVTK---EP 307
Cdd:cd05080   3 KRYLKKIRDLGEGHFGKVSLYCYDPTNDgtgemVAVKALKAdcGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEqggKS 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDegsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-- 385
Cdd:cd05080  83 LQLIMEYVPLGSLRDYLPKH---SIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVpe 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 -DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTY------GRVPYPGMSNPE--------VIRNLER 450
Cdd:cd05080 160 gHEYYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHcdssqsPPTKFLEMIGIAqgqmtvvrLIELLER 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 33469982 451 GYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLEDFY 494
Cdd:cd05080 240 GERLPCPDKCPQEVYH-LMKNCWETEASFRPTFENLIPILKTVH 282
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
241-493 6.95e-44

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: 156.63  E-value: 6.95e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYY-----KNNMKVAIKTLKEGTMSPEA--FLGEANVMKALQHERLVRLYAVVTKEP---IYI 310
Cdd:cd05079   6 LKRIRDLGEGHFGKVELCRYdpegdNTGEQVAVKSLKPESGGNHIadLKKEIEILRNLYHENIVKYKGICTEDGgngIKL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE-- 388
Cdd:cd05079  86 IMEFLPSGSLKEYLPRNK-NKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDke 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 -YTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMS------NP--------EVIRNLERGYR 453
Cdd:cd05079 165 yYTVKDDLDSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCDSESSPMTlflkmiGPthgqmtvtRLVRVLEEGKR 244
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 33469982 454 MPRPDTCPPELYRgVIAECWRSRPEERPTFeflQSVLEDF 493
Cdd:cd05079 245 LPRPPNCPEEVYQ-LMRKCWEFQPSKRTTF---QNLIEGF 280
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
242-481 2.08e-43

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 160.18  E-value: 2.08e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKN-NMKVAIKTLK-EGTMSPEA---FLGEANVMKALQHERLVRLYAVVTKEPI-YIVTEYM 315
Cdd:COG0515  10 RILRLLGRGGMGVVYLARDLRlGRPVALKVLRpELAADPEArerFRREARALARLNHPNIVRVYDVGEEDGRpYLVMEYV 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGA 395
Cdd:COG0515  90 EGESLADLLR--RRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGT 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 kfpIKWT----APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMP----RPDtCPPELyRG 467
Cdd:COG0515 168 ---VVGTpgymAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPPpselRPD-LPPAL-DA 241
                       250
                ....*....|....
gi 33469982 468 VIAECWRSRPEERP 481
Cdd:COG0515 242 IVLRALAKDPEERY 255
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
247-483 3.33e-43

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


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 155.16  E-value: 3.33e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNN---MKVAIKTLKEGTMSPEA--FLGEANVMKAL-QHERLVRLY-AVVTKEPIYIVTEYMARGC 319
Cdd:cd05088  15 IGEGNFGQVLKARIKKDglrMDAAIKRMKEYASKDDHrdFAGELEVLCKLgHHPNIINLLgACEHRGYLYLAIEYAPHGN 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLK------TD--------EGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIi 385
Cdd:cd05088  95 LLDFLRksrvleTDpafaiansTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG- 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 DSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELY 465
Cdd:cd05088 174 QEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVY 253
                       250
                ....*....|....*...
gi 33469982 466 RgVIAECWRSRPEERPTF 483
Cdd:cd05088 254 D-LMRQCWREKPYERPSF 270
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
247-491 5.99e-41

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: 147.26  E-value: 5.99e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLKEGTMSpeaflgEANVMKALQHERLVRLYAVVTKEPIY-IVTEYMARGCLLDFLK 325
Cdd:cd14059   1 LGSGAQGAVFLGKFRGE-EVAVKKVRDEKET------DIKHLRKLNHPNIIKFKGVCTQAPCYcILMEYCPYGQLYEVLR 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 326 tdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIdSEYTAQEGAKFPIKWTAPE 405
Cdd:cd14059  74 --AGREITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKEL-SEKSTKMSFAGTVAWMAPE 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 406 AIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNL-ERGYRMPRPDTCPPELyRGVIAECWRSRPEERPTFE 484
Cdd:cd14059 151 VIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIIWGVgSNSLQLPVPSTCPDGF-KLLMKQCWNSKPRNRPSFR 228

                ....*..
gi 33469982 485 FLQSVLE 491
Cdd:cd14059 229 QILMHLD 235
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
247-491 9.14e-41

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: 147.15  E-value: 9.14e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLK-----EGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYmARGCL 320
Cdd:cd14061   2 IGVGGFGKVYRGIWRGE-EVAVKAARqdpdeDISVTLENVRQEARLFWMLRHPNIIALRGVCLQPPnLCLVMEY-ARGGA 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDflKTDEGSRLSLPRLIDMSAQIAEGMAYIER---MNSIHRDLRAANILVSEAL--------CCKIADFGLARiiDSEY 389
Cdd:cd14061  80 LN--RVLAGRKIPPHVLVDWAIQIARGMNYLHNeapVPIIHRDLKSSNILILEAIenedlenkTLKITDFGLAR--EWHK 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGmsnpevIRNLERGYR-------MPRPDTCpP 462
Cdd:cd14061 156 TTRMSAAGTYAWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKG------IDGLAVAYGvavnkltLPIPSTC-P 227
                       250       260
                ....*....|....*....|....*....
gi 33469982 463 ELYRGVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14061 228 EPFAQLMKDCWQPDPHDRPSFADILKQLE 256
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
247-491 2.64e-40

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: 146.00  E-value: 2.64e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmkVAIKTLKEGTMSPE---AFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd14062   1 IGSGSFGTVYKGRWHGD--VAVKKLNVTDPTPSqlqAFKNEVAVLRKTRHVNILLFMGYMTKPQLAIVTQWCEGSSLYKH 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLArIIDSEYTAQEGAKFP---IK 400
Cdd:cd14062  79 LHVLE-TKFEMLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLA-TVKTRWSGSQQFEQPtgsIL 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 WTAPEAIHFGV---FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPE-VIRNLERGYRMP-----RPDTcpPELYRGVIAE 471
Cdd:cd14062 157 WMAPEVIRMQDenpYSFQSDVYAFGIVLYELLT-GQLPYSHINNRDqILFMVGRGYLRPdlskvRSDT--PKALRRLMED 233
                       250       260
                ....*....|....*....|
gi 33469982 472 CWRSRPEERPTFEFLQSVLE 491
Cdd:cd14062 234 CIKFQRDERPLFPQILASLE 253
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
242-482 5.96e-40

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: 144.97  E-value: 5.96e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEAFLG---EANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd14003   3 ELGKTLGEGSFGKVKLARHKlTGEKVAIKIIDKSKLKEEIEEKikrEIEIMKLLNHPNIIKLYEVIeTENKIYLVMEYAS 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEgsRLSLP--RLIdmSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEYTAQ 392
Cdd:cd14003  83 GGELFDYIVNNG--RLSEDeaRRF--FQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFrgGSLLKTF 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKFpikWTAPEAI-HFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYrMPRPDTCPPELyRGVIAE 471
Cdd:cd14003 159 CGTPA---YAAPEVLlGRKYDGPKADVWSLGVILYAMLT-GYLPFDDDNDSKLFRKILKGK-YPIPSHLSPDA-RDLIRR 232
                       250
                ....*....|.
gi 33469982 472 CWRSRPEERPT 482
Cdd:cd14003 233 MLVVDPSKRIT 243
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
247-493 1.16e-39

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: 144.72  E-value: 1.16e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIKTLKEGTM--SPEAFLGEANVMKALQHERLVRLYAVVTK--EPIyIVTEYMARGCLLD 322
Cdd:cd14066   1 IGSGGFGTVYKGVLENGTVVAVKRLNEMNCaaSKKEFLTELEMLGRLRHPNLVRLLGYCLEsdEKL-LVYEYMPNGSLED 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLKTDEGSR-LSLPRLIDMSAQIAEGMAYIERMNS---IHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE--GAK 396
Cdd:cd14066  80 RLHCHKGSPpLPWPQRLKIAKGIARGLEYLHEECPppiIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVSKtsAVK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 397 FPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVT------YGRVPYPGMSNPEVIRNLERGYRM----PRPDTCPP---- 462
Cdd:cd14066 160 GTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLTgkpavdENRENASRKDLVEWVESKGKEELEdildKRLVDDDGveee 239
                       250       260       270
                ....*....|....*....|....*....|....
gi 33469982 463 ---ELYRgVIAECWRSRPEERPTFEFLQSVLEDF 493
Cdd:cd14066 240 eveALLR-LALLCTRSDPSLRPSMKEVVQMLEKL 272
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
247-483 2.89e-39

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: 143.36  E-value: 2.89e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMSPE---AFLGEANVMKALQHERLVRLYAV-VTKEPIYIVTEYMARGCLL 321
Cdd:cd13978   1 LGSGGFGTVSKARHVSwFGMVAIKCLHSSPNCIEerkALLKEAEKMERARHSYVLPLLGVcVERRSLGLVMEYMENGSLK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLKTDEGSrLSLPRLIDMSAQIAEGMAYIERMNS--IHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFP- 398
Cdd:cd13978  81 SLLEREIQD-VPWSLRFRIIHEIALGMNFLHNMDPplLHHDLKPENILLDNHFHVKISDFGLSKLGMKSISANRRRGTEn 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 ----IKWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVI-RNLERGYR-------MPRPDTCPPEL 464
Cdd:cd13978 160 lggtPIYMAPEAFDDFNkkPTSKSDVYSFAIVIWAVLT-RKEPFENAINPLLImQIVSKGDRpslddigRLKQIENVQEL 238
                       250
                ....*....|....*....
gi 33469982 465 YRgVIAECWRSRPEERPTF 483
Cdd:cd13978 239 IS-LMIRCWDGNPDARPTF 256
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
120-219 7.23e-39

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 136.96  E-value: 7.23e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDV-TTQGELIKHYKIRCLDEGGYYISPRITFPSL 198
Cdd:cd10367   1 QAEEWYFGKIGRKDAERQLLSPGNPRGAFLIRESETTKGAYSLSIRDWdQNRGDHVKHYKIRKLDTGGYYITTRAQFDTV 80
                        90       100
                ....*....|....*....|.
gi 33469982 199 QALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10367  81 QELVQHYMEVNDGLCYLLTAP 101
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
122-219 1.66e-38

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: 135.90  E-value: 1.66e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 122 ERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDV-TTQGELIKHYKIRCLDEGGYYISPRITFPSLQA 200
Cdd:cd10418   3 EEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWdDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQ 82
                        90
                ....*....|....*....
gi 33469982 201 LVQHYSKKGDGLCQRLTLP 219
Cdd:cd10418  83 LVQHYSERAAGLCCRLVVP 101
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
109-213 4.14e-38

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: 134.93  E-value: 4.14e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 109 PSNFVARVesleMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQGEL-IKHYKIRCLDEGGY 187
Cdd:cd10344   1 PSNYVAKV----YHGWLFEGLSREKAEELLMLPGNQVGSFLIRESETRRGCYSLSVRHRGSQSRDsVKHYRIFRLDNGWF 76
                        90       100
                ....*....|....*....|....*.
gi 33469982 188 YISPRITFPSLQALVQHYSKKGDGLC 213
Cdd:cd10344  77 YISPRLTFQCLEDMVNHYSESADGLC 102
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
122-219 5.29e-38

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 134.39  E-value: 5.29e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 122 ERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVT-TQGELIKHYKIRCLDEGGYYISPRITFPSLQA 200
Cdd:cd10368   3 EEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDdMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQ 82
                        90
                ....*....|....*....
gi 33469982 201 LVQHYSKKGDGLCQRLTLP 219
Cdd:cd10368  83 LVQHYSETANGLCKVLIVT 101
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
239-491 1.64e-37

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: 138.62  E-value: 1.64e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYYKNNMkVAIKTLKEG-----TMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVT 312
Cdd:cd14147   3 QELRLEEVIGIGGFGKVYRGSWRGEL-VAVKAARQDpdediSVTAESVRQEARLFAMLAHPNIIALKAVCLEEPnLCLVM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKtdeGSRLSLPRLIDMSAQIAEGMAYIER---MNSIHRDLRAANILVS--------EALCCKIADFGL 381
Cdd:cd14147  82 EYAAGGPLSRALA---GRRVPPHVLVNWAVQIARGMHYLHCealVPVIHRDLKSNNILLLqpienddmEHKTLKITDFGL 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 382 ARiiDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLE-RGYRMPRPDTC 460
Cdd:cd14147 159 AR--EWHKTTQMSAAGTYAWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAvNKLTLPIPSTC 235
                       250       260       270
                ....*....|....*....|....*....|.
gi 33469982 461 pPELYRGVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14147 236 -PEPFAQLMADCWAQDPHRRPDFASILQQLE 265
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
247-492 1.86e-37

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: 138.20  E-value: 1.86e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLKEG-----TMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYmARGCL 320
Cdd:cd14148   2 IGVGGFGKVYKGLWRGE-EVAVKAARQDpdediAVTAENVRQEARLFWMLQHPNIIALRGVCLNPPhLCLVMEY-ARGGA 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDflKTDEGSRLSLPRLIDMSAQIAEGMAYIER---MNSIHRDLRAANILVSEAL--------CCKIADFGLARiiDSEY 389
Cdd:cd14148  80 LN--RALAGKKVPPHVLVNWAVQIARGMNYLHNeaiVPIIHRDLKSSNILILEPIenddlsgkTLKITDFGLAR--EWHK 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG-YRMPRPDTCpPELYRGV 468
Cdd:cd14148 156 TTKMSAAGTYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAMNkLTLPIPSTC-PEPFARL 233
                       250       260
                ....*....|....*....|....
gi 33469982 469 IAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd14148 234 LEECWDPDPHGRPDFGSILKRLED 257
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
232-493 2.04e-37

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: 138.66  E-value: 2.04e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 232 DEWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNmkVAIKTLKEGTMSPE---AFLGEANVMKALQHERLVRLYAVVTKEPI 308
Cdd:cd14151   1 DDWEIPDGQITVGQRIGSGSFGTVYKGKWHGD--VAVKMLNVTAPTPQqlqAFKNEVGVLRKTRHVNILLFMGYSTKPQL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 YIVTEYMARGCLLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLArIIDSE 388
Cdd:cd14151  79 AIVTQWCEGSSLYHHLHIIE-TKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLA-TVKSR 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQ---EGAKFPIKWTAPEAIHF---GVFTIKADVWSFGVLLMEVVTyGRVPYPGMSN-PEVIRNLERGYRMPR----P 457
Cdd:cd14151 157 WSGShqfEQLSGSILWMAPEVIRMqdkNPYSFQSDVYAFGIVLYELMT-GQLPYSNINNrDQIIFMVGRGYLSPDlskvR 235
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 33469982 458 DTCPPELYRgVIAECWRSRPEERPTFEFLQSVLEDF 493
Cdd:cd14151 236 SNCPKAMKR-LMAECLKKKRDERPLFPQILASIELL 270
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
247-484 4.23e-37

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: 136.97  E-value: 4.23e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCLL 321
Cdd:cd14009   1 IGRGSFATVWKGRHKqTGEVVAIKEISRKKLNKklqENLESEIAILKSIKHPNIVRLYDVQkTEDFIYLVLEYCAGGDLS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLKTDEGSRLSLPRLIdMSaQIAEGMAYIERMNSIHRDLRAANILVS---EALCCKIADFGLARIIDSEYTAQEGAKFP 398
Cdd:cd14009  81 QYIRKRGRLPEAVARHF-MQ-QLASGLKFLRSKNIIHRDLKPQNLLLStsgDDPVLKIADFGFARSLQPASMAETLCGSP 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 IkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCP---PELyRGVIAECWRS 475
Cdd:cd14009 159 L-YMAPEILQFQKYDAKADLWSVGAILFEMLV-GKPPFRGSNHVQLLRNIERSDAVIPFPIAAqlsPDC-KDLLRRLLRR 235

                ....*....
gi 33469982 476 RPEERPTFE 484
Cdd:cd14009 236 DPAERISFE 244
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
243-491 5.93e-37

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: 137.07  E-value: 5.93e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNmkVAIKTLKEGTMSPE---AFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARGC 319
Cdd:cd14150   4 MLKRIGTGSFGTVFRGKWHGD--VAVKILKVTEPTPEqlqAFKNEMQVLRKTRHVNILLFMGFMTRPNFAIITQWCEGSS 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLArIIDSEYTAQEGAKFP- 398
Cdd:cd14150  82 LYRHLHVTE-TRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLA-TVKTRWSGSQQVEQPs 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 --IKWTAPEAIHF---GVFTIKADVWSFGVLLMEVVTyGRVPYPGMSN-PEVIRNLERGYRMPR----PDTCPPELYRgV 468
Cdd:cd14150 160 gsILWMAPEVIRMqdtNPYSFQSDVYAYGVVLYELMS-GTLPYSNINNrDQIIFMVGRGYLSPDlsklSSNCPKAMKR-L 237
                       250       260
                ....*....|....*....|...
gi 33469982 469 IAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14150 238 LIDCLKFKREERPLFPQILVSIE 260
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
246-486 3.17e-36

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: 134.66  E-value: 3.17e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPEAF---LGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCL 320
Cdd:cd06627   7 LIGRGAFGSVYKGLNLNTGEfVAIKQISLEKIPKSDLksvMGEIDLLKKLNHPNIVKYIGSVkTKDSLYIILEYVENGSL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTDegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPIK 400
Cdd:cd06627  87 ASIIKKF--GKFPESLVAVYIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVATKLNEVEKDENSVVGTPY 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 WTAPEAIHFGVFTIKADVWSFGVLLMEVVT-----YGRVPYPGMSNpevIRNLErgyRMPRPDTCPPELyRGVIAECWRS 475
Cdd:cd06627 165 WMAPEVIEMSGVTTASDIWSVGCTVIELLTgnppyYDLQPMAALFR---IVQDD---HPPLPENISPEL-RDFLLQCFQK 237
                       250
                ....*....|.
gi 33469982 476 RPEERPTFEFL 486
Cdd:cd06627 238 DPTLRPSAKEL 248
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
234-491 3.40e-36

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: 135.54  E-value: 3.40e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLVRKLGSGQFGEVWMGYYKNNmkVAIKTLKEGTMSPE---AFLGEANVMKALQHERLVRLYAVVTKEPIYI 310
Cdd:cd14149   7 WEIEASEVMLSTRIGSGSFGTVYKGKWHGD--VAVKILKVVDPTPEqfqAFRNEVAVLRKTRHVNILLFMGYMTKDNLAI 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLArIIDSEYT 390
Cdd:cd14149  85 VTQWCEGSSLYKHLHVQE-TKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLA-TVKSRWS 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 391 AQEGAKFP---IKWTAPEAIHF---GVFTIKADVWSFGVLLMEVVTyGRVPYPGMSN-PEVIRNLERGYRMPRPD----T 459
Cdd:cd14149 163 GSQQVEQPtgsILWMAPEVIRMqdnNPFSFQSDVYSYGIVLYELMT-GELPYSHINNrDQIIFMVGRGYASPDLSklykN 241
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 460 CPPELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14149 242 CPKAMKR-LVADCIKKVKEERPLFPQILSSIE 272
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
242-486 3.60e-36

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


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 134.64  E-value: 3.60e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPEAFLG-EANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARG 318
Cdd:cd05122   3 EILEKIGKGGFGVVYKARHKKTGQiVAIKKINLESKEKKESILnEIAILKKCKHPNIVKYYgSYLKKDELWIVMEFCSGG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKtdegsrlSLPRLIDmSAQIA-------EGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd05122  83 SLKDLLK-------NTNKTLT-EQQIAyvckevlKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTR 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QE--GAKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVtYGRVPYPGMSNPEVIrnlergYRMPRPDtcPPEL----- 464
Cdd:cd05122 155 NTfvGTPY---WMAPEVIQGKPYGFKADIWSLGITAIEMA-EGKPPYSELPPMKAL------FLIATNG--PPGLrnpkk 222
                       250       260
                ....*....|....*....|....*.
gi 33469982 465 ----YRGVIAECWRSRPEERPTFEFL 486
Cdd:cd05122 223 wskeFKDFLKKCLQKDPEKRPTAEQL 248
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
248-491 9.60e-36

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: 133.16  E-value: 9.60e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 248 GSGQFGEVWMGYY-KNNMKVAIKTLKEgtmspeaFLGEANVMKALQHERLVRLYAVVTKEPIY-IVTEYMARGCLLDFLK 325
Cdd:cd14060   2 GGGSFGSVYRAIWvSQDKEVAVKKLLK-------IEKEAEILSVLSHRNIIQFYGAILEAPNYgIVTEYASYGSLFDYLN 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 326 TDEGSRLSLPRLIDMSAQIAEGMAYIER---MNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPikWT 402
Cdd:cd14060  75 SNESEEMDMDQIMTWATDIAKGMHYLHMeapVKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSLVGTFP--WM 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 403 APEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVI-RNLERGYRMPRPDTCPPElYRGVIAECWRSRPEERP 481
Cdd:cd14060 153 APEVIQSLPVSETCDTYSYGVVLWEMLTR-EVPFKGLEGLQVAwLVVEKNERPTIPSSCPRS-FAELMRRCWEADVKERP 230
                       250
                ....*....|
gi 33469982 482 TFEFLQSVLE 491
Cdd:cd14060 231 SFKQIIGILE 240
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
247-483 2.24e-35

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: 132.85  E-value: 2.24e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLKEG-----TMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYmARGCL 320
Cdd:cd14146   2 IGVGGFGKVYRATWKGQ-EVAVKAARQDpdediKATAESVRQEAKLFSMLRHPNIIKLEGVCLEEPnLCLVMEF-ARGGT 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LD--------FLKTDEGSRLSLPRLIDMSAQIAEGMAYIER---MNSIHRDLRAANILVSEAL--------CCKIADFGL 381
Cdd:cd14146  80 LNralaaanaAPGPRRARRIPPHILVNWAVQIARGMLYLHEeavVPILHRDLKSSNILLLEKIehddicnkTLKITDFGL 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 382 ARiiDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLE-RGYRMPRPDTC 460
Cdd:cd14146 160 AR--EWHRTTKMSAAGTYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGVAvNKLTLPIPSTC 236
                       250       260
                ....*....|....*....|...
gi 33469982 461 pPELYRGVIAECWRSRPEERPTF 483
Cdd:cd14146 237 -PEPFAKLMKECWEQDPHIRPSF 258
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
247-494 2.82e-35

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: 132.63  E-value: 2.82e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIktLKEGTMSPE----AFLGEANVMKALQHERLVRLYAVVTK-EPIYIVTEYMARGCLL 321
Cdd:cd14154   1 LGKGFFGQAIKVTHRETGEVMV--MKELIRFDEeaqrNFLKEVKVMRSLDHPNVLKFIGVLYKdKKLNLITEYIPGGTLK 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYT------AQEGA 395
Cdd:cd14154  79 DVLK-DMARPLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLIVEERLpsgnmsPSETL 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPIK--------------WTAPEAIHFGVFTIKADVWSFGVLLMEVVtyGRVPypgmSNPEVI-RNL-----ERGYRMP 455
Cdd:cd14154 158 RHLKSpdrkkrytvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVLCEII--GRVE----ADPDYLpRTKdfglnVDSFREK 231
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 33469982 456 RPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLEDFY 494
Cdd:cd14154 232 FCAGCPPPFFK-LAFLCCDLDPEKRPPFETLEEWLEALY 269
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
120-219 1.19e-34

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: 125.31  E-value: 1.19e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDvttqGELIKHYKIRCLDEGGYYISPRITFPSLQ 199
Cdd:cd10370   1 EAEPWYFGKIKRIEAEKKLLLPENEHGAFLIRDSESRHNDYSLSVRD----GDTVKHYRIRQLDEGGFFIARRTTFRTLQ 76
                        90       100
                ....*....|....*....|
gi 33469982 200 ALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10370  77 ELVEHYSKDSDGLCVNLRKP 96
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
122-218 1.24e-34

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 125.56  E-value: 1.24e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 122 ERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVT-TQGELIKHYKIRCLDEGGYYISPRITFPSLQA 200
Cdd:cd10419   3 EEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDdMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQ 82
                        90
                ....*....|....*...
gi 33469982 201 LVQHYSKKGDGLCQRLTL 218
Cdd:cd10419  83 LVQHYSEKADGLCFNLTV 100
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
120-217 1.67e-34

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: 125.16  E-value: 1.67e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDV-TTQGELIKHYKIRCLDEGGYYISPRITFPSL 198
Cdd:cd10365   1 QAEEWYFGKITRRESERLLLNAENPRGTFLVRESETTKGAYCLSVSDFdNAKGLNVKHYKIRKLDSGGFYITSRTQFNSL 80
                        90
                ....*....|....*....
gi 33469982 199 QALVQHYSKKGDGLCQRLT 217
Cdd:cd10365  81 QQLVAYYSKHADGLCHRLT 99
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
243-458 8.11e-34

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: 128.36  E-value: 8.11e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKN-NMKVAIKTL---KEGTMSPEAFLGEANVMKALQHERLVRLYAV-VTKEPIYIVTEYMAR 317
Cdd:cd05117   4 LGKVLGRGSFGVVRLAVHKKtGEEYAVKIIdkkKLKSEDEEMLRREIEILKRLDHPNIVKLYEVfEDDKNLYLVMELCTG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV---SEALCCKIADFGLARIIDSEYTAQEG 394
Cdd:cd05117  84 GELFDRIV--KKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLaskDPDSPIKIIDFGLAKIFEEGEKLKTV 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 395 AKFPIkWTAPEAIHFGVFTIKADVWSFGVLLmevvtY----GRVPYPGMSNPEVIRNLERG-YRMPRPD 458
Cdd:cd05117 162 CGTPY-YVAPEVLKGKGYGKKCDIWSLGVIL-----YillcGYPPFYGETEQELFEKILKGkYSFDSPE 224
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
235-483 9.22e-34

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: 128.62  E-value: 9.22e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYYkNNMKVAIKTLKEG-----TMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-I 308
Cdd:cd14145   2 EIDFSELVLEEIIGIGGFGKVYRAIW-IGDEVAVKAARHDpdediSQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPnL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 YIVTEYmARGCLLDflKTDEGSRLSLPRLIDMSAQIAEGMAYIER---MNSIHRDLRAANILVSEAL--------CCKIA 377
Cdd:cd14145  81 CLVMEF-ARGGPLN--RVLSGKRIPPDILVNWAVQIARGMNYLHCeaiVPVIHRDLKSSNILILEKVengdlsnkILKIT 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 378 DFGLARiiDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG-YRMPR 456
Cdd:cd14145 158 DFGLAR--EWHRTTKMSAAGTYAWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYGVAMNkLSLPI 234
                       250       260
                ....*....|....*....|....*..
gi 33469982 457 PDTCpPELYRGVIAECWRSRPEERPTF 483
Cdd:cd14145 235 PSTC-PEPFARLMEDCWNPDPHSRPPF 260
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
247-494 1.75e-33

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: 127.17  E-value: 1.75e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNnMKVAIKTLkEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLDFLK 325
Cdd:cd14058   1 VGRGSFGVVCKARWRN-QIVAVKII-ESESEKKAFEVEVRQLSRVDHPNIIKLYgACSNQKPVCLVMEYAEGGSLYNVLH 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 326 TDEGS-RLSLPRLIDMSAQIAEGMAYIERMNS---IHRDLRAANIL-VSEALCCKIADFGLARIIDSEYTAQEGAkfpIK 400
Cdd:cd14058  79 GKEPKpIYTAAHAMSWALQCAKGVAYLHSMKPkalIHRDLKPPNLLlTNGGTVLKICDFGTACDISTHMTNNKGS---AA 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 WTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIR--NLERGYRMPRPDTCPPELyRGVIAECWRSRPE 478
Cdd:cd14058 156 WMAPEVFEGSKYSEKCDVFSWGIILWEVITR-RKPFDHIGGPAFRImwAVHNGERPPLIKNCPKPI-ESLMTRCWSKDPE 233
                       250
                ....*....|....*.
gi 33469982 479 ERPTFEFLQSVLEDFY 494
Cdd:cd14058 234 KRPSMKEIVKIMSHLM 249
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
247-483 2.49e-33

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: 126.84  E-value: 2.49e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIktLKEGTMSPE--AFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMARGCLLDF 323
Cdd:cd14065   1 LGKGFFGEVYKVTHRETGKVMV--MKELKRFDEqrSFLKEVKLMRRLSHPNILRFIGVCVKDnKLNFITEYVNGGTLEEL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCK---IADFGLARIIDSEYTAQEGAKFPIK 400
Cdd:cd14065  79 LKSMD-EQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREANRGRnavVADFGLAREMPDEKTKKPDRKKRLT 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 ------WTAPEAIHFGVFTIKADVWSFGVLLMEVVtyGRVPypgmSNPEVIRNLE------RGYRMPRPDTCPPELYRgV 468
Cdd:cd14065 158 vvgspyWMAPEMLRGESYDEKVDVFSFGIVLCEII--GRVP----ADPDYLPRTMdfgldvRAFRTLYVPDCPPSFLP-L 230
                       250
                ....*....|....*
gi 33469982 469 IAECWRSRPEERPTF 483
Cdd:cd14065 231 AIRCCQLDPEKRPSF 245
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
120-219 4.18e-33

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 121.14  E-value: 4.18e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDvttqGELIKHYKIRCLDEGGYYISPRITFPSLQ 199
Cdd:cd10369   1 QAEPWFFGAIKRADAEKQLLYSENQTGAFLIRESESQKGEFSLSVLD----GGVVKHYRIRRLDEGGFFLTRRKTFSTLN 76
                        90       100
                ....*....|....*....|
gi 33469982 200 ALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10369  77 EFVNYYTTTSDGLCVKLGKP 96
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
240-482 5.40e-33

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: 126.34  E-value: 5.40e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWMGYYKNNmKVAIKTLK---EGTMSPEAFLGEANVMKaLQHERLVRLYAVVTKEPI----YIVT 312
Cdd:cd13979   4 PLRLQEPLGSGGFGSVYKATYKGE-TVAVKIVRrrrKNRASRQSFWAELNAAR-LRHENIVRVLAAETGTDFaslgLIIM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLktDEGS-RLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd13979  82 EYCGNGTLQQLI--YEGSePLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEGNEV 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKfPIKWT----APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMsNPEVIRNLErGYRMpRPDTCPPE---- 463
Cdd:cd13979 160 GTPRS-HIGGTytyrAPELLKGERVTPKADIYSFGITLWQMLT-RELPYAGL-RQHVLYAVV-AKDL-RPDLSGLEdsef 234
                       250       260
                ....*....|....*....|.
gi 33469982 464 --LYRGVIAECWRSRPEERPT 482
Cdd:cd13979 235 gqRLRSLISRCWSAQPAERPN 255
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
120-217 1.39e-32

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 119.74  E-value: 1.39e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDV-TTQGELIKHYKIRCLDEGGYYISPRITFPSL 198
Cdd:cd10366   1 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWdEVRGDNVKHYKIRKLDNGGYYITTRAQFDTL 80
                        90
                ....*....|....*....
gi 33469982 199 QALVQHYSKKGDGLCQRLT 217
Cdd:cd10366  81 QKLVKHYTEHADGLCHKLT 99
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
245-492 4.41e-32

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: 124.53  E-value: 4.41e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYyKNNMKVAIKTLKE--GTMSPE---AFLGEANVMKALQHERLVRLYAVVTKEPIY-IVTEYMARG 318
Cdd:cd14158  21 NKLGEGGFGVVFKGY-INDKNVAVKKLAAmvDISTEDltkQFEQEIQVMAKCQHENLVELLGYSCDGPQLcLVYTYMPNG 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLK-TDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR--IIDSEYTAQEGA 395
Cdd:cd14158 100 SLLDRLAcLNDTPPLSWHMRCKIAQGTANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARasEKFSQTIMTERI 179
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPIKWTAPEAIHfGVFTIKADVWSFGVLLMEVVT------YGRVPYPGMSNPEVIRNLERGY------RMPRPDTCPPE 463
Cdd:cd14158 180 VGTTAYMAPEALR-GEITPKSDIFSFGVVLLEIITglppvdENRDPQLLLDIKEEIEDEEKTIedyvdkKMGDWDSTSIE 258
                       250       260
                ....*....|....*....|....*....
gi 33469982 464 LYRGVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd14158 259 AMYSVASQCLNDKKNRRPDIAKVQQLLQE 287
Pkinase pfam00069
Protein kinase domain;
241-484 6.35e-32

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 121.97  E-value: 6.35e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   241 LRLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYM 315
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRdTGKIVAIKKIKkekIKKKKDKNILREIKILKKLNHPNIVRLYdAFEDKDNLYLVLEYV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   316 ARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYiermnsihrdlraanilvsealcckiadfglariiDSEYTAQEGA 395
Cdd:pfam00069  81 EGGSLFDLLS--EKGAFSEREAKFIMKQILEGLES-----------------------------------GSSLTTFVGT 123
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   396 KFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGM-SNPEVIRNLERGYRMPR-PDTCPPELyRGVIAECW 473
Cdd:pfam00069 124 PW---YMAPEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPGInGNEIYELIIDQPYAFPElPSNLSEEA-KDLLKKLL 198
                         250
                  ....*....|.
gi 33469982   474 RSRPEERPTFE 484
Cdd:pfam00069 199 KKDPSKRLTAT 209
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
242-482 8.80e-32

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: 122.57  E-value: 8.80e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMgyYKNNM---KVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEY 314
Cdd:cd08215   3 EKIRVIGKGSFGSAYL--VRRKSdgkLYVLKEIDLSNMSEkerEEALNEVKLLSKLKHPNIVKYYeSFEENGKLCIVMEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKTDEGSRLSLP--RLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEytaQ 392
Cdd:cd08215  81 ADGGDLAQKIKKQKKKGQPFPeeQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKVLEST---T 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKfpikwT--------APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPEL 464
Cdd:cd08215 158 DLAK-----TvvgtpyylSPELCENKPYNYKSDIWALGCVLYELCT-LKHPFEANNLPALVYKIVKGQYPPIPSQYSSEL 231
                       250
                ....*....|....*...
gi 33469982 465 yRGVIAECWRSRPEERPT 482
Cdd:cd08215 232 -RDLVNSMLQKDPEKRPS 248
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
247-486 2.15e-31

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: 121.74  E-value: 2.15e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNN-----MKVaIKTLKEGTMSPEA---FLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMAR 317
Cdd:cd06632   8 LGSGSFGSVYEGFNGDTgdffaVKE-VSLVDDDKKSRESvkqLEQEIALLSKLRHPNIVQYYGTEREEdNLYIFLEYVPG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSLPRLidMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ--EGA 395
Cdd:cd06632  87 GSIHKLLQRYGAFEEPVIRL--YTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVEAFSFAKsfKGS 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFpikWTAPEAI---HFGvFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPR-PDTCPPELyRGVIAE 471
Cdd:cd06632 165 PY---WMAPEVImqkNSG-YGLAVDIWSLGCTVLEMAT-GKPPWSQYEGVAAIFKIGNSGELPPiPDHLSPDA-KDFIRL 238
                       250
                ....*....|....*
gi 33469982 472 CWRSRPEERPTFEFL 486
Cdd:cd06632 239 CLQRDPEDRPTASQL 253
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
242-441 3.72e-31

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: 120.80  E-value: 3.72e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPEAFLGEANVMKAL----QHERLVRLYAVVTKEP---IYIVTE 313
Cdd:cd05118   2 EVLRKIGEGAFGTVWLARdKVTGEKVAIKKIKNDFRHPKAALREIKLLKHLndveGHPNIVKLLDVFEHRGgnhLCLVFE 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGcLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC-CKIADFGLARIIDSEYTAQ 392
Cdd:cd05118  82 LMGMN-LYELIK-DYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGqLKLADFGLARSFTSPPYTP 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 33469982 393 EGAkfPIKWTAPEAIhFG--VFTIKADVWSFGVLLMEVVTyGRVPYPGMSN 441
Cdd:cd05118 160 YVA--TRWYRAPEVL-LGakPYGSSIDIWSLGCILAELLT-GRPLFPGDSE 206
SH3_Blk cd12009
Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of ...
62-115 5.15e-31

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212942 [Multi-domain]  Cd Length: 54  Bit Score: 114.14  E-value: 5.15e-31
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVAR 115
Cdd:cd12009   1 CVIAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWLAKSLTTGKEGYIPSNYVAR 54
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
247-482 1.72e-30

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: 119.58  E-value: 1.72e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKN-NMKVAIKT-----LKEGTMSPEAFLGEAN----------VMKALQHERLVRLYAVV---TKEP 307
Cdd:cd14008   1 LGRGSFGKVKLALDTEtGQLYAIKIfnksrLRKRREGKNDRGKIKNalddvrreiaIMKKLDHPNIVRLYEVIddpESDK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS 387
Cdd:cd14008  81 LYLVLEYCEGGPVMELDSGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFED 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYTAQEGAK----FpikwTAPEAIHFGVFTI---KADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNLERGYRM-PRPDT 459
Cdd:cd14008 161 GNDTLQKTAgtpaF----LAPELCDGDSKTYsgkAADIWALGVTLY-CLVFGRLPFNGDNILELYEAIQNQNDEfPIPPE 235
                       250       260
                ....*....|....*....|...
gi 33469982 460 CPPELyRGVIAECWRSRPEERPT 482
Cdd:cd14008 236 LSPEL-KDLLRRMLEKDPEKRIT 257
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
246-486 6.31e-30

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: 117.70  E-value: 6.31e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd06614   7 KIGEGASGEVYKATDRAtGKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYdSYLVGDELWVVMEYMDGGSLTDI 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEY---TAQEGAKFpik 400
Cdd:cd06614  87 I-TQNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKskrNSVVGTPY--- 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 WTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY---PGMSNPEVIRNLerGY-RMPRPDTCPPELyRGVIAECWRSR 476
Cdd:cd06614 163 WMAPEVIKRKDYGPKVDIWSLGIMCIEMAE-GEPPYleePPLRALFLITTK--GIpPLKNPEKWSPEF-KDFLNKCLVKD 238
                       250
                ....*....|
gi 33469982 477 PEERPTFEFL 486
Cdd:cd06614 239 PEKRPSAEEL 248
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
243-491 9.48e-30

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: 116.81  E-value: 9.48e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKN-NMKVAIK-----TLKEGTMSpEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYM 315
Cdd:cd14007   4 IGKPLGKGKFGNVYLAREKKsGFIVALKvisksQLQKSGLE-HQLRREIEIQSHLRHPNILRLYGYFeDKKRIYLILEYA 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKTDegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS-------- 387
Cdd:cd14007  83 PNGELYKELKKQ--KRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSVHAPSnrrktfcg 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 --EYtaqegakfpikwTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG-YRMprPDTCPPEL 464
Cdd:cd14007 161 tlDY------------LPPEMVEGKEYDYKVDIWSLGVLCYELLV-GKPPFESKSHQETYKRIQNVdIKF--PSSVSPEA 225
                       250       260
                ....*....|....*....|....*..
gi 33469982 465 yRGVIAECWRSRPEERPTfefLQSVLE 491
Cdd:cd14007 226 -KDLISKLLQKDPSKRLS---LEQVLN 248
SH2 pfam00017
SH2 domain;
124-205 9.58e-30

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 111.15  E-value: 9.58e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   124 WFFRSQGRKEAERQLLApINKAGSFLIRESETNKGAFSLSVKDvttqGELIKHYKIRCLDEGGYYISPRITFPSLQALVQ 203
Cdd:pfam00017   1 WYHGKISRQEAERLLLN-GKPDGTFLVRESESTPGGYTLSVRD----DGKVKHYKIQSTDNGGYYISGGVKFSSLAELVE 75

                  ..
gi 33469982   204 HY 205
Cdd:pfam00017  76 HY 77
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
247-493 9.91e-30

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: 117.36  E-value: 9.91e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNN-----MKVAIKTLKEgtmSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCL 320
Cdd:cd14221   1 LGKGCFGQAIKVTHRETgevmvMKELIRFDEE---TQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKrLNFITEYIKGGTL 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPIK 400
Cdd:cd14221  78 RGIIKSMD-SHYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDEKTQPEGLRSLKK 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 --------------WTAPEAIHFGVFTIKADVWSFGVLLMEVVtyGRVPypgmSNPEVI-RNLERGYRMPR------PDT 459
Cdd:cd14221 157 pdrkkrytvvgnpyWMAPEMINGRSYDEKVDVFSFGIVLCEII--GRVN----ADPDYLpRTMDFGLNVRGfldrycPPN 230
                       250       260       270
                ....*....|....*....|....*....|....
gi 33469982 460 CPPELYRgVIAECWRSRPEERPTFEFLQSVLEDF 493
Cdd:cd14221 231 CPPSFFP-IAVLCCDLDPEKRPSFSKLEHWLETL 263
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
239-484 1.31e-29

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: 116.72  E-value: 1.31e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEAFLG----EANVMKALQHERLVRLYAVV-TKEPIYIVT 312
Cdd:cd14073   1 HRYELLETLGKGTYGKVKLAIERaTGREVAIKSIKKDKIEDEQDMVrirrEIEIMSSLNHPHIIRIYEVFeNKDKIVIVM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLktDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ 392
Cdd:cd14073  81 EYASGGELYDYI--SERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKDKLLQ 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKFPIkWTAPEAIHFGVFT-IKADVWSFGVLLMEVVtYGRVPYPGMSNPEVIRNLERG-YRMPrpdtCPPELYRGVIA 470
Cdd:cd14073 159 TFCGSPL-YASPEIVNGTPYQgPEVDCWSLGVLLYTLV-YGTMPFDGSDFKRLVKQISSGdYREP----TQPSDASGLIR 232
                       250
                ....*....|....
gi 33469982 471 ECWRSRPEERPTFE 484
Cdd:cd14073 233 WMLTVNPKRRATIE 246
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
247-495 1.47e-29

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: 116.83  E-value: 1.47e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPE---AFLGEANVMKALQHERLVRLYAVVTKEPIY-IVTEYMARGCLLD 322
Cdd:cd14027   1 LDSGGFGKVSLCFHRTQGLVVLKTVYTGPNCIEhneALLEEGKMMNRLRHSRVVKLLGVILEEGKYsLVMEYMEKGNLMH 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLKtdegsRLSLP-----RLIdmsAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA--------------- 382
Cdd:cd14027  81 VLK-----KVSVPlsvkgRII---LEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLAsfkmwskltkeehne 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 -RIIDSEYTAQEGAKFpikWTAPEaiHFGVF----TIKADVWSFGVLLMEVVTyGRVPYPGMSNPE----VIRNLERGYR 453
Cdd:cd14027 153 qREVDGTAKKNAGTLY---YMAPE--HLNDVnakpTEKSDVYSFAIVLWAIFA-NKEPYENAINEDqiimCIKSGNRPDV 226
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 33469982 454 MPRPDTCPPELYrGVIAECWRSRPEERPTFEFLQSVLEDFYT 495
Cdd:cd14027 227 DDITEYCPREII-DLMKLCWEANPEARPTFPGIEEKFRPFYL 267
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
257-493 1.99e-29

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: 116.93  E-value: 1.99e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 257 MGYYKNNMkVAIKTL----KEGTMSpeaFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLDFL-----KT 326
Cdd:cd14042  25 TGYYKGNL-VAIKKVnkkrIDLTRE---VLKELKHMRDLQHDNLTRFIgACVDPPNICILTEYCPKGSLQDILenediKL 100
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 327 DEGSRLSLprLIDmsaqIAEGMAYIErmNSI---HRDLRAANILVSEALCCKIADFGLARIIDS-EYTAQEGAKFPIK-W 401
Cdd:cd14042 101 DWMFRYSL--IHD----IVKGMHYLH--DSEiksHGNLKSSNCVVDSRFVLKITDFGLHSFRSGqEPPDDSHAYYAKLlW 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 402 TAPEAIHFGVF----TIKADVWSFGVLLMEVVTYGRVPY---PGMSNPEVI-RNLERGYRMP-RPDT----CPPELyRGV 468
Cdd:cd14042 173 TAPELLRDPNPpppgTQKGDVYSFGIILQEIATRQGPFYeegPDLSPKEIIkKKVRNGEKPPfRPSLdeleCPDEV-LSL 251
                       250       260
                ....*....|....*....|....*
gi 33469982 469 IAECWRSRPEERPTFEFLQSVLEDF 493
Cdd:cd14042 252 MQRCWAEDPEERPDFSTLRNKLKKL 276
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
243-486 3.09e-29

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: 115.92  E-value: 3.09e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARG 318
Cdd:cd06610   5 LIEVIGSGATAVVYAAYCLpKKEKVAIKRIDLEKCQTsmDELRKEIQAMSQCNHPNVVSYYtSFVVGDELWLVMPLLSGG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTdegsrlSLPRLIDMSAQIA-------EGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd06610  85 SLLDIMKS------SYPRGGLDEAIIAtvlkevlKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSASLATGGDR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIK----WTAPEAIHFGV-FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGyRMPRPDTCPP---- 462
Cdd:cd06610 159 TRKVRKTFVgtpcWMAPEVMEQVRgYDFKADIWSFGITAIELAT-GAAPYSKYPPMKVLMLTLQN-DPPSLETGADykky 236
                       250       260
                ....*....|....*....|....*
gi 33469982 463 -ELYRGVIAECWRSRPEERPTFEFL 486
Cdd:cd06610 237 sKSFRKMISLCLQKDPSKRPTAEEL 261
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
258-484 4.73e-29

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: 115.57  E-value: 4.73e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 258 GYYKNNMkVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCLLDFL-----KTDEGSR 331
Cdd:cd13992  21 GVYGGRT-VAIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPnIAVVTEYCTRGSLQDVLlnreiKMDWMFK 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 332 LSLPRlidmsaQIAEGMAYIErmNSI---HRDLRAANILVSEALCCKIADFGLARIIdSEYTAQEGAKFPIK----WTAP 404
Cdd:cd13992 100 SSFIK------DIVKGMNYLH--SSSigyHGRLKSSNCLVDSRWVVKLTDFGLRNLL-EEQTNHQLDEDAQHkkllWTAP 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 405 EAI------HFGvfTIKADVWSFGVLLMEVVTYGRvPYPGMSN-PEVIRNLERGYRMPRP------DTCPPELYRgVIAE 471
Cdd:cd13992 171 ELLrgslleVRG--TQKGDVYSFAIILYEILFRSD-PFALEREvAIVEKVISGGNKPFRPelavllDEFPPRLVL-LVKQ 246
                       250
                ....*....|...
gi 33469982 472 CWRSRPEERPTFE 484
Cdd:cd13992 247 CWAENPEKRPSFK 259
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
242-430 6.02e-29

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: 115.15  E-value: 6.02e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNN-MKVAIKTLKEGTMSPE------AFLGEANVMKALQHERLVRLYAVVT-KEPIYIVTE 313
Cdd:cd06625   3 KQGKLLGQGAFGQVYLCYDADTgRELAVKQVEIDPINTEaskevkALECEIQLLKNLQHERIVQYYGCLQdEKSLSIFME 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTdEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE 393
Cdd:cd06625  83 YMPGGSVKDEIKA-YGA-LTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRLQTICSSTG 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 33469982 394 GAKF---PIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd06625 161 MKSVtgtPY-WMSPEVINGEGYGRKADIWSVGCTVVEMLT 199
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
244-484 4.19e-28

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


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 112.77  E-value: 4.19e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYK---NNMKVAIKTLKE--GTMSPEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVTEYMAR 317
Cdd:cd05087   2 LKEIGHGWFGKVFLGEVNsglSSTQVVVKELKAsaSVQDQMQFLEEAQPYRALQHTNLLQCLAQCAEvTPYLLVMEFCPL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSLPR---LIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA--RIIDSEYTAQ 392
Cdd:cd05087  82 GDLKGYLRSCRAAESMAPDpltLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLShcKYKEDYFVTA 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKFPIKWTAPEAI---HFGVF----TIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNL--ERGYRMPRPDTCPP- 462
Cdd:cd05087 162 DQLWVPLRWIAPELVdevHGNLLvvdqTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLTYTvrEQQLKLPKPQLKLSl 241
                       250       260
                ....*....|....*....|...
gi 33469982 463 -ELYRGVIAECWRsRPEERPTFE 484
Cdd:cd05087 242 aERWYEVMQFCWL-QPEQRPTAE 263
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
245-490 5.65e-28

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: 112.68  E-value: 5.65e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNMKVAIKTLKE-----GTMSPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTEYMARG 318
Cdd:cd05042   1 QEIGNGWFGKVLLGEIYSGTSVAQVVVKElkasaNPKEQDTFLKEGQPYRILQHPNILQcLGQCVEAIPYLLVMEFCDLG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEGSRL--SLPRLID-MSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA--RIIDSEYTAQE 393
Cdd:cd05042  81 DLKAYLRSEREHERgdSDTRTLQrMACEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAhsRYKEDYIETDD 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFPIKWTAPE---AIHFGVFTI----KADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNL--ERGYRMPRPDTCPP-- 462
Cdd:cd05042 161 KLWFPLRWTAPElvtEFHDRLLVVdqtkYSNIWSLGVTLWELFENGAQPYSNLSDLDVLAQVvrEQDTKLPKPQLELPys 240
                       250       260
                ....*....|....*....|....*...
gi 33469982 463 ELYRGVIAECWRSrPEERPTFEFLQSVL 490
Cdd:cd05042 241 DRWYEVLQFCWLS-PEQRPAAEDVHLLL 267
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
240-488 7.07e-28

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


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 111.91  E-value: 7.07e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEG--TMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYM 315
Cdd:cd06623   2 DLERVKVLGQGSSGVVYKVRHKpTGKIYALKKIHVDgdEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEgEISIVLEYM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERM-NSIHRDLRAANILVSEALCCKIADFGLARIIDSeyTAQEG 394
Cdd:cd06623  82 DGGSLADLLKKVGK--IPEPVLAYIARQILKGLDYLHTKrHIIHRDIKPSNLLINSKGEVKIADFGISKVLEN--TLDQC 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKF--PIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYP---GMSNPEVIRNLERG--YRMPrPDTCPPELyRG 467
Cdd:cd06623 158 NTFvgTVTYMSPERIQGESYSYAADIWSLGLTLLECAL-GKFPFLppgQPSFFELMQAICDGppPSLP-AEEFSPEF-RD 234
                       250       260
                ....*....|....*....|..
gi 33469982 468 VIAECWRSRPEERPT-FEFLQS 488
Cdd:cd06623 235 FISACLQKDPKKRPSaAELLQH 256
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
237-482 1.50e-27

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


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 110.82  E-value: 1.50e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLkEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEY 314
Cdd:cd06612   1 PEEVFDILEKLGEGSYGSVYKAIHKeTGQVVAIKVV-PVEEDLQEIIKEISILKQCDSPYIVKYYGSYFKNTdLWIVMEY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKTdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE- 393
Cdd:cd06612  80 CGAGSVSDIMKI-TNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTDTMAKRNt 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 --GAKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY---PGMSNPEVIRNlergyrMPRPDTCPPE----L 464
Cdd:cd06612 159 viGTPF---WMAPEVIQEIGYNNKADIWSLGITAIEMAE-GKPPYsdiHPMRAIFMIPN------KPPPTLSDPEkwspE 228
                       250
                ....*....|....*...
gi 33469982 465 YRGVIAECWRSRPEERPT 482
Cdd:cd06612 229 FNDFVKKCLVKDPEERPS 246
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
243-440 2.38e-27

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: 111.09  E-value: 2.38e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMG-YYKNNMKVAIKTLKEGTMSPEAFLGEANVmKALQ----HERLVRLYAVV-TKEPIYIVTEYMa 316
Cdd:cd07830   3 VIKQLGDGTFGSVYLArNKETGELVAIKKMKKKFYSWEECMNLREV-KSLRklneHPNIVKLKEVFrENDELYFVFEYM- 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE--YTAQEG 394
Cdd:cd07830  81 EGNLYQLMKDRKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRSRppYTDYVS 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 33469982 395 AkfpiKW-TAPEAI-HFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMS 440
Cdd:cd07830 161 T----RWyRAPEILlRSTSYSSPVDIWALGCIMAELYT-LRPLFPGSS 203
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
241-491 3.34e-27

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: 110.52  E-value: 3.34e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNNmkVAIKTLKEGTMSPE---AFLGEANVMKALQHERLVRLYAVVTKEPIY-IVTEYmA 316
Cdd:cd14063   2 LEIKEVIGKGRFGRVHRGRWHGD--VAIKLLNIDYLNEEqleAFKEEVAAYKNTRHDNLVLFMGACMDPPHLaIVTSL-C 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEalcCK--IADFGLARIIDSEYTAQE- 393
Cdd:cd14063  79 KGRTLYSLIHERKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLEN---GRvvITDFGLFSLSGLLQPGRRe 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 -GAKFPIKWT---APEAI----------HFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDT 459
Cdd:cd14063 156 dTLVIPNGWLcylAPEIIralspdldfeESLPFTKASDVYAFGTVWYELLA-GRWPFKEQPAESIIWQVGCGKKQSLSQL 234
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 460 CPPELYRGVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14063 235 DIGREVKDILMQCWAYDPEKRPTFSDLLRMLE 266
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
243-488 6.90e-27

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: 109.04  E-value: 6.90e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMS---PEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMAR 317
Cdd:cd08529   4 ILNKLGKGSFGVVYKVVRKVDGRVyALKQIDISRMSrkmREEAIDEARVLSKLNSPYVIKYYdSFVDKGKLNIVMEYAEN 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTAQEGAK 396
Cdd:cd08529  84 GDLHSLIKSQRGRPLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILsDTTNFAQTIVG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 397 FPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWRSR 476
Cdd:cd08529 164 TPY-YLSPELCEDKPYNEKSDVWALGCVLYELCT-GKHPFEAQNQGALILKIVRGKYPPISASYSQDLSQ-LIDSCLTKD 240
                       250
                ....*....|...
gi 33469982 477 PEERP-TFEFLQS 488
Cdd:cd08529 241 YRQRPdTTELLRN 253
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
247-491 8.92e-27

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: 109.26  E-value: 8.92e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIktLKEGTMSPE----AFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCLL 321
Cdd:cd14222   1 LGKGFFGQAIKVTHKATGKVMV--MKELIRCDEetqkTFLTEVKVMRSLDHPNVLKFIGVLYKDKrLNLLTEFIEGGTLK 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPIK- 400
Cdd:cd14222  79 DFLRADD--PFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRLIVEEKKKPPPDKPTTKk 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 -------------------WTAPEAIHFGVFTIKADVWSFGVLLMEVVtyGRVpypgMSNPEVI-RNLERGYRMPR---- 456
Cdd:cd14222 157 rtlrkndrkkrytvvgnpyWMAPEMLNGKSYDEKVDIFSFGIVLCEII--GQV----YADPDCLpRTLDFGLNVRLfwek 230
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 33469982 457 --PDTCPPELYrGVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14222 231 fvPKDCPPAFF-PLAAICCRLEPDSRPAFSKLEDSFE 266
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
239-482 1.61e-26

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: 108.49  E-value: 1.61e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYYK-NNMKVAIKT--LKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEY 314
Cdd:cd06609   1 ELFTLLERIGKGSFGEVYKGIDKrTNQVVAIKVidLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLKGsKLWIIMEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKT---DEGSRLSLPRlidmsaQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd06609  81 CGGGSVLDLLKPgplDETYIAFILR------EVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTSTMSK 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QE---GAKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLergyrmprPDTCPPEL---- 464
Cdd:cd06609 155 RNtfvGTPF---WMAPEVIKQSGYDEKADIWSLGITAIELAK-GEPPLSDLHPMRVLFLI--------PKNNPPSLegnk 222
                       250       260
                ....*....|....*....|..
gi 33469982 465 ----YRGVIAECWRSRPEERPT 482
Cdd:cd06609 223 fskpFKDFVELCLNKDPKERPS 244
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
244-462 2.16e-26

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: 108.81  E-value: 2.16e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMSpEAFLG-------EANVMKALQHERLVRLYAV-VTKEPIYIVTEY 314
Cdd:cd07841   5 GKKLGEGTYAVVYKARDKEtGRIVAIKKIKLGERK-EAKDGinftalrEIKLLQELKHPNIIGLLDVfGHKSNINLVFEF 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGclLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS---EYTA 391
Cdd:cd07841  84 METD--LEKVIKDKSIVLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLARSFGSpnrKMTH 161
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 392 QEGAKFpikWTAPE----AIHFGVftiKADVWSFGVLLMEVVTygRVPY-PGMSNpevIRNLERGYRM---PRPDTCPP 462
Cdd:cd07841 162 QVVTRW---YRAPEllfgARHYGV---GVDMWSVGCIFAELLL--RVPFlPGDSD---IDQLGKIFEAlgtPTEENWPG 229
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
244-441 2.18e-26

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: 108.34  E-value: 2.18e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKN-NMKVAIKTLK-----EGTmsPEAFLGEANVMKALQHERLVRLYAV-VTKEPIYIVTEYMA 316
Cdd:cd07829   4 LEKLGEGTYGVVYKAKDKKtGEIVALKKIRldneeEGI--PSTALREISLLKELKHPNIVKLLDViHTENKLYLVFEYCD 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGcLLDFLKTdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIdseytaqegaK 396
Cdd:cd07829  82 QD-LKKYLDK-RPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAF----------G 149
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 397 FPIK---------W-TAPEaIHFG--VFTIKADVWSFGVLLMEVVTyGRVPYPGMSN 441
Cdd:cd07829 150 IPLRtythevvtlWyRAPE-ILLGskHYSTAVDIWSVGCIFAELIT-GKPLFPGDSE 204
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
247-492 3.19e-26

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: 107.70  E-value: 3.19e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLKEGTMSPEA----------------------FLGEANVMKALQHERLVRLYAVVT 304
Cdd:cd14000   2 LGDGGFGSVYRASYKGE-PVAVKIFNKHTSSNFAnvpadtmlrhlratdamknfrlLRQELTVLSHLHHPSIVYLLGIGI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 305 KePIYIVTEYMARGCLLDFLKTDEGSRLSLPRLI--DMSAQIAEGMAYIERMNSIHRDLRAANILV-----SEALCCKIA 377
Cdd:cd14000  81 H-PLMLVLELAPLGSLDHLLQQDSRSFASLGRTLqqRIALQVADGLRYLHSAMIIYRDLKSHNVLVwtlypNSAIIIKIA 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 378 DFGLARiidseYTAQEGAK----FPiKWTAPEAIHFGV-FTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLErGY 452
Cdd:cd14000 160 DYGISR-----QCCRMGAKgsegTP-GFRAPEIARGNViYNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEFDIHG-GL 232
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 33469982 453 RMP--RPDTCPPELYRGVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd14000 233 RPPlkQYECAPWPEVEVLMKKCWKENPQQRPTAVTVVSILNS 274
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
247-492 4.11e-26

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: 106.84  E-value: 4.11e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMkVAIKTLKEGTMSPEA----FLGEANVMKALQHERLVRLYAVVTKEP--IYIVTEYMARGCL 320
Cdd:cd14064   1 IGSGSFGKVYKGRCRNKI-VAIKRYRANTYCSKSdvdmFCREVSILCRLNHPCVIQFVGACLDDPsqFAIVTQYVSGGSL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTDEgsrlslpRLIDMSAQ------IAEGMAYIERMNS--IHRDLRAANILVSEALCCKIADFGLARII----DSE 388
Cdd:cd14064  80 FSLLHEQK-------RVIDLQSKliiavdVAKGMEYLHNLTQpiIHRDLNSHNILLYEDGHAVVADFGESRFLqsldEDN 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGAkfpIKWTAPEAI-HFGVFTIKADVWSFGVLLMEVVTyGRVPY----PGMSNPEVIRNLER---GYRMPRPDTc 460
Cdd:cd14064 153 MTKQPGN---LRWMAPEVFtQCTRYSIKADVFSYALCLWELLT-GEIPFahlkPAAAAADMAYHHIRppiGYSIPKPIS- 227
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 461 ppelyrGVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd14064 228 ------SLLMRGWNAEPESRPSFVEIVALLEP 253
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
242-484 9.82e-26

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: 105.88  E-value: 9.82e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEA--FLG-EANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd14075   5 RIRGELGSGNFSQVKLGIHQlTKEKVAIKILDKTKLDQKTqrLLSrEISSMEKLHHPNIIRLYEVVeTLSKLHLVMEYAS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAK 396
Cdd:cd14075  85 GGEL--YTKISTEGKLSESEAKPLFAQIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFSTHAKRGETLNTFCG 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 397 FPiKWTAPE----AIHFGVFTikaDVWSFGVLLMEVVTyGRVPYPGMSNPEVIRN-LERGYRMPR--PDTCpPELYRGVI 469
Cdd:cd14075 163 SP-PYAAPElfkdEHYIGIYV---DIWALGVLLYFMVT-GVMPFRAETVAKLKKCiLEGTYTIPSyvSEPC-QELIRGIL 236
                       250
                ....*....|....*
gi 33469982 470 aecwRSRPEERPTFE 484
Cdd:cd14075 237 ----QPVPSDRYSID 247
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
244-427 1.28e-25

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: 105.84  E-value: 1.28e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYK-NNMKVAIKT--LKEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGC 319
Cdd:cd13996  11 IELLGSGGFGSVYKVRNKvDGVTYAIKKirLTEKSSASEKVLREVKALAKLNHPNIVRYYtAWVEEPPLYIQMELCEGGT 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLktdeGSRLSLPRL-----IDMSAQIAEGMAYIERMNSIHRDLRAANILVS-EALCCKIADFGLARII-------- 385
Cdd:cd13996  91 LRDWI----DRRNSSSKNdrklaLELFKQILKGVSYIHSKGIVHRDLKPSNIFLDnDDLQVKIGDFGLATSIgnqkreln 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 33469982 386 ---------DSEYTAQEGAKFpikWTAPEAIHFGVFTIKADVWSFGVLLME 427
Cdd:cd13996 167 nlnnnnngnTSNNSVGIGTPL---YASPEQLDGENYNEKADIYSLGIILFE 214
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
122-211 1.39e-25

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: 100.00  E-value: 1.39e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982    122 ERWFFRSQGRKEAERQLLAPINkaGSFLIRESETNKGAFSLSVKDvttqGELIKHYKIRCLDEGGYYISPRITFPSLQAL 201
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEGD--GDFLVRDSESSPGDYVLSVRV----KGKVKHYRIRRNEDGKFYLEGGRKFPSLVEL 74
                           90
                   ....*....|
gi 33469982    202 VQHYSKKGDG 211
Cdd:smart00252  75 VEHYQKNSLG 84
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
247-483 2.00e-25

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: 105.26  E-value: 2.00e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNN-------MKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARG 318
Cdd:cd05037   7 LGQGTFTNIYDGILREVgdgrvqeVEVLLKVLDsDHRDISESFFETASLMSQISHKHLVKLYGVCVADENIMVQEYVRYG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA------LCCKIADFGLARIIDSEYTAQ 392
Cdd:cd05037  87 PLDKYLRR-MGNNVPLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNILLAREgldgypPFIKLSDPGVPITVLSREERV 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EgakfPIKWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTcpPELYRgVIA 470
Cdd:cd05037 166 D----RIPWIAPECLRNLQanLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAPDC--AELAE-LIM 238
                       250
                ....*....|...
gi 33469982 471 ECWRSRPEERPTF 483
Cdd:cd05037 239 QCWTYEPTKRPSF 251
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
242-443 2.05e-25

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: 105.72  E-value: 2.05e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMK-VAIKTL-----KEGtmSPEAFLGEANVMKALQHERLVRLYAVVTKEP-------I 308
Cdd:cd07840   2 EKIAQIGEGTYGQVYKARNKKTGElVALKKIrmeneKEG--FPITAIREIKLLQKLDHPNVVRLKEIVTSKGsakykgsI 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 YIVTEYMARgcllDF--LKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID 386
Cdd:cd07840  80 YMVFEYMDH----DLtgLLDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYT 155
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SEytaqegakFPIKWT---------APE----AIHFGVftiKADVWSFGVLLMEVVTyGRVPYPGMSNPE 443
Cdd:cd07840 156 KE--------NNADYTnrvitlwyrPPElllgATRYGP---EVDMWSVGCILAELFT-GKPIFQGKTELE 213
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
242-484 3.18e-25

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: 104.26  E-value: 3.18e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYY-KNNMKVAIKTLKEGTMSPEAFL----GEANVMKALQHERLVRLYAVV-TKEPIYIVTEYM 315
Cdd:cd14081   4 RLGKTLGKGQTGLVKLAKHcVTGQKVAIKIVNKEKLSKESVLmkveREIAIMKLIEHPNVLKLYDVYeNKKYLYLVLEYV 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGA 395
Cdd:cd14081  84 SGGELFDYLV--KKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMASLQPEGSLLETSC 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPiKWTAPEAI----HFGvftIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG-YRMprPDTCPPE---LYRG 467
Cdd:cd14081 162 GSP-HYACPEVIkgekYDG---RKADIWSCGVILYALLV-GALPFDDDNLRQLLEKVKRGvFHI--PHFISPDaqdLLRR 234
                       250
                ....*....|....*..
gi 33469982 468 VIaecwRSRPEERPTFE 484
Cdd:cd14081 235 ML----EVNPEKRITIE 247
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
239-486 3.48e-25

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: 104.35  E-value: 3.48e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPE--AFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEY 314
Cdd:cd06605   1 DDLEYLGELGEGNGGVVSKVRHRpSGQIMAVKVIRLEIDEALqkQILRELDVLHKCNSPYIVGFYgAFYSEGDISICMEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYI-ERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYTAQ 392
Cdd:cd06605  81 MDGGSLDKILK--EVGRIPERILGKIAVAVVKGLIYLhEKHKIIHRDVKPSNILVNSRGQVKLCDFGVSgQLVDSLAKTF 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYP---GMSNPEVIRNLERGYRMPRP----DTCPPELy 465
Cdd:cd06605 159 VGTR---SYMAPERISGGKYTVKSDIWSLGLSLVELAT-GRFPYPppnAKPSMMIFELLSYIVDEPPPllpsGKFSPDF- 233
                       250       260
                ....*....|....*....|.
gi 33469982 466 RGVIAECWRSRPEERPTFEFL 486
Cdd:cd06605 234 QDFVSQCLQKDPTERPSYKEL 254
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
247-492 6.92e-25

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: 103.37  E-value: 6.92e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTEYMARGCLLDFLK 325
Cdd:cd14156   1 IGSGFFSKVYKVTHGATGKVMVVKIYKNDVDQHKIVREISLLQKLSHPNIVRyLGICVKDEKLHPILEYVSGGCLEELLA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 326 TDEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV---SEALCCKIADFGLARIIDSEYTAQEGAKFPIK-- 400
Cdd:cd14156  81 REELP-LSWREKVELACDISRGMVYLHSKNIYHRDLNSKNCLIrvtPRGREAVVTDFGLAREVGEMPANDPERKLSLVgs 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 --WTAPEAIHFGVFTIKADVWSFGVLLMEVVtyGRVPypgmSNPEVI-RNLERGYRMPR-PDTCP--PELYRGVIAECWR 474
Cdd:cd14156 160 afWMAPEMLRGEPYDRKVDVFSFGIVLCEIL--ARIP----ADPEVLpRTGDFGLDVQAfKEMVPgcPEPFLDLAASCCR 233
                       250
                ....*....|....*...
gi 33469982 475 SRPEERPTFEFLQSVLED 492
Cdd:cd14156 234 MDAFKRPSFAELLDELED 251
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
247-484 1.55e-24

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: 102.45  E-value: 1.55e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNN--MKVAIKTL-KEGTMSPEAFLG-EANVMKALQHERLVRLYAV-VTKEPIYIVTEYMARGCLL 321
Cdd:cd14120   1 IGHGAFAVVFKGRHRKKpdLPVAIKCItKKNLSKSQNLLGkEIKILKELSHENVVALLDCqETSSSVYLVMEYCNGGDLA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLKTdEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA---------LCCKIADFGLARIIDSEYTAQ 392
Cdd:cd14120  81 DYLQA-KGT-LSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHNsgrkpspndIRLKIADFGFARFLQDGMMAA 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKFPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGmSNPEVIRNLERGYR--MPR-PDTCPPELyRGVI 469
Cdd:cd14120 159 TLCGSPM-YMAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPFQA-QTPQELKAFYEKNAnlRPNiPSGTSPAL-KDLL 234
                       250
                ....*....|....*
gi 33469982 470 AECWRSRPEERPTFE 484
Cdd:cd14120 235 LGLLKRNPKDRIDFE 249
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
240-484 2.30e-24

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: 101.69  E-value: 2.30e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKE---GTMSPEAFLGEANVMKAL-QHERLVRLY-AVVTKEPIYIVTE 313
Cdd:cd13997   1 HFHELEQIGSGSFSEVFKVRSKvDGCLYAVKKSKKpfrGPKERARALREVEAHAALgQHPNIVRYYsSWEEGGHLYIQME 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTD-EGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ 392
Cdd:cd13997  81 LCENGSLQDALEELsPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLETSGDVE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKfpiKWTAPEAIH-FGVFTIKADVWSFGVLLMEVVTYGRVPypgmSNPEVIRNLERGYrMPRPDTCP--PELYRgVI 469
Cdd:cd13997 161 EGDS---RYLAPELLNeNYTHLPKADIFSLGVTVYEAATGEPLP----RNGQQWQQLRQGK-LPLPPGLVlsQELTR-LL 231
                       250
                ....*....|....*
gi 33469982 470 AECWRSRPEERPTFE 484
Cdd:cd13997 232 KVMLDPDPTRRPTAD 246
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
233-461 2.93e-24

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: 102.01  E-value: 2.93e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLrlvrkLGSGQFGEVWMGYY--KNNMKVAIKTL-KEGTMSPEAFLG-EANVMKALQHERLVRLYAVVT-KEP 307
Cdd:cd14202   1 KFEFSRKDL-----IGHGAFAVVFKGRHkeKHDLEVAVKCInKKNLAKSQTLLGkEIKILKELKHENIVALYDFQEiANS 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGSRLSLPRLidMSAQIAEGMAYIERMNSIHRDLRAANILVS---------EALCCKIAD 378
Cdd:cd14202  76 VYLVMEYCNGGDLADYLHTMRTLSEDTIRL--FLQQIAGAMKMLHSKGIIHRDLKPQNILLSysggrksnpNNIRIKIAD 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 379 FGLARIIDSEYTAQEGAKFPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGmSNPEVIRNLERGYR----- 453
Cdd:cd14202 154 FGFARYLQNNMMAATLCGSPM-YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPFQA-SSPQDLRLFYEKNKslspn 230

                ....*...
gi 33469982 454 MPRPDTCP 461
Cdd:cd14202 231 IPRETSSH 238
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
242-484 4.07e-24

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: 101.49  E-value: 4.07e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNM---KVAIKTLKEgTMSPEAFLG-----EANVMKALQHERLVRLYAVVTKEP-IYIVT 312
Cdd:cd14080   3 RLGKTIGEGSYSKVKLAEYTKSGlkeKVACKIIDK-KKAPKDFLEkflprELEILRKLRHPNIIQVYSIFERGSkVFIFM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTdeGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ 392
Cdd:cd14080  82 EYAEHGDLLEYIQK--RGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLCPDDDGDV 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKF--PIKWTAPEAIHfgvfTI-----KADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRN-LERGYRMPRPDTCPPEL 464
Cdd:cd14080 160 LSKTFcgSAAYAAPEILQ----GIpydpkKYDIWSLGVILYIMLC-GSMPFDDSNIKKMLKDqQNRKVRFPSSVKKLSPE 234
                       250       260
                ....*....|....*....|
gi 33469982 465 YRGVIAECWRSRPEERPTFE 484
Cdd:cd14080 235 CKDLIDQLLEPDPTKRATIE 254
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
243-482 5.80e-24

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: 101.01  E-value: 5.80e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMKV-AIKTL-----KEGTMSPEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVTEYM 315
Cdd:cd14098   4 IIDRLGSGTFAEVKKAVEVETGKMrAIKQIvkrkvAGNDKNLQLFQREINILKSLEHPGIVRLIDWYEDdQHIYLVMEYV 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLkTDEGSrlsLPRLI--DMSAQIAEGMAYIERMNSIHRDLRAANILVSE--ALCCKIADFGLARIIDSEyTA 391
Cdd:cd14098  84 EGGDLMDFI-MAWGA---IPEQHarELTKQILEAMAYTHSMGITHRDLKPENILITQddPVIVKISDFGLAKVIHTG-TF 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAI------HFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG--YRMPRPDTCPPE 463
Cdd:cd14098 159 LVTFCGTMAYLAPEILmskeqnLQGGYSNLVDMWSVGCLVYVMLT-GALPFDGSSQLPVEKRIRKGryTQPPLVDFNISE 237
                       250
                ....*....|....*....
gi 33469982 464 LYRGVIAECWRSRPEERPT 482
Cdd:cd14098 238 EAIDFILRLLDVDPEKRMT 256
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
245-447 1.15e-23

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: 100.55  E-value: 1.15e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNM-KVAIKTLKEGTMS---------PEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTE 313
Cdd:cd14084  12 RTLGSGACGEVKLAYDKSTCkKVAIKIINKRKFTigsrreinkPRNIETEIEILKKLSHPCIIKIEDFFDAEDdYYIVLE 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTDEGSRLSLPRLIdmSAQIAEGMAYIERMNSIHRDLRAANILVS---EALCCKIADFGLARIIDSEYT 390
Cdd:cd14084  92 LMEGGELFDRVVSNKRLKEAICKLY--FYQMLLAVKYLHSNGIIHRDLKPENVLLSsqeEECLIKITDFGLSKILGETSL 169
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 391 AQEGAKFPIkWTAPEA-IHFGV--FTIKADVWSFGVLLMevVTYGRVP-----YPGMSNPEVIRN 447
Cdd:cd14084 170 MKTLCGTPT-YLAPEVlRSFGTegYTRAVDCWSLGVILF--ICLSGYPpfseeYTQMSLKEQILS 231
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
244-487 1.26e-23

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: 99.92  E-value: 1.26e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVwmgyYK-----NNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLY-AVVTKEP--IYIVT 312
Cdd:cd08217   5 LETIGKGSFGTV----RKvrrksDGKILVWKEIDYGKMSEkekQQLVSEVNILRELKHPNIVRYYdRIVDRANttLYIVM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLK--TDEGSRLSLPRLIDMSAQIAEGMAYIERMNS-----IHRDLRAANILVSEALCCKIADFGLARII 385
Cdd:cd08217  81 EYCEGGDLAQLIKkcKKENQYIPEEFIWKIFTQLLLALYECHNRSVgggkiLHRDLKPANIFLDSDNNVKLGDFGLARVL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 DSEytaQEGAK----FPIKWtAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCP 461
Cdd:cd08217 161 SHD---SSFAKtyvgTPYYM-SPELLNEQSYDEKSDIWSLGCLIYELCA-LHPPFQAANQLELAKKIKEGKFPRIPSRYS 235
                       250       260
                ....*....|....*....|....*..
gi 33469982 462 PELYRgVIAECWRSRPEERP-TFEFLQ 487
Cdd:cd08217 236 SELNE-VIKSMLNVDPDKRPsVEELLQ 261
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
247-456 1.68e-23

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: 99.68  E-value: 1.68e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKN-NMKVAIKTLKEgTMSPEAFLG-----EANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGC 319
Cdd:cd14162   8 LGHGSYAVVKKAYSTKhKCKVAIKIVSK-KKAPEDYLQkflprEIEVIKGLKHPNLICFYEAIeTTSRVYIIMELAENGD 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiidSEYTAQEGAKFPI 399
Cdd:cd14162  87 LLDYIRKN--GALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFAR---GVMKTKDGKPKLS 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 400 K-------WTAPEAIHF----GVFtikADVWSFGVLLMEVVtYGRVPYPGMSNPEVIRNLERGYRMPR 456
Cdd:cd14162 162 EtycgsyaYASPEILRGipydPFL---SDIWSMGVVLYTMV-YGRLPFDDSNLKVLLKQVQRRVVFPK 225
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
240-492 1.97e-23

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: 99.72  E-value: 1.97e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTM-SPEAFLGEANVMKAL-QHERLVRLY--AVVTKEP---IYIV 311
Cdd:cd13985   1 RYQVTKQLGEGGFSYVYLAHDVNtGRRYALKRMYFNDEeQLRVAIKEIEIMKRLcGHPNIVQYYdsAILSSEGrkeVLLL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYmARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNS--IHRDLRAANILVSEALCCKIADFGLARIIDSEY 389
Cdd:cd13985  81 MEY-CPGSLVDILEKSPPSPLSEEEVLRIFYQICQAVGHLHSQSPpiIHRDIKIENILFSNTGRFKLCDFGSATTEHYPL 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQEGAKFPI----KWT-----APEAIH-FGVFTI--KADVWSFGVLLMEVVTygrvpypgMSNP----EVIRNLERGYR 453
Cdd:cd13985 160 ERAEEVNIIEeeiqKNTtpmyrAPEMIDlYSKKPIgeKADIWALGCLLYKLCF--------FKLPfdesSKLAIVAGKYS 231
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 33469982 454 MPRPDTCPPELyRGVIAECWRSRPEERP-TFEFLQSVLED 492
Cdd:cd13985 232 IPEQPRYSPEL-HDLIRHMLTPDPAERPdIFQVINIITKD 270
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
247-430 2.04e-23

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: 99.49  E-value: 2.04e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIKTLK-EGTMSPE-AFLGEANVMKALQHERLVRLYA-VVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd14664   1 IGRGGAGTVYKGVMPNGTLVAVKRLKgEGTQGGDhGFQAEIQTLGMIRHRNIVRLRGyCSNPTTNLLVYEYMPNGSLGEL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LKTDEGSRLSL--PRLIDMSAQIAEGMAYIERMNS---IHRDLRAANILVSEALCCKIADFGLARIIDseYTAQE---GA 395
Cdd:cd14664  81 LHSRPESQPPLdwETRQRIALGSARGLAYLHHDCSpliIHRDVKSNNILLDEEFEAHVADFGLAKLMD--DKDSHvmsSV 158
                       170       180       190
                ....*....|....*....|....*....|....*
gi 33469982 396 KFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd14664 159 AGSYGYIAPEYAYTGKVSEKSDVYSYGVVLLELIT 193
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
242-455 2.48e-23

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: 99.13  E-value: 2.48e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd14072   3 RLLKTIGKGNFAKVKLARHVlTGREVAIKIIDKTQLNPsslQKLFREVRIMKILNHPNIVKLFEVIeTEKTLYLVMEYAS 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLktdegsrLSLPRLIDMSA-----QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAriidSEYTA 391
Cdd:cd14072  83 GGEVFDYL-------VAHGRMKEKEArakfrQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFS----NEFTP 151
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 392 qeGAKFPI-----KWTAPEaihfgVFTIK------ADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG-YRMP 455
Cdd:cd14072 152 --GNKLDTfcgspPYAAPE-----LFQGKkydgpeVDVWSLGVILYTLVS-GSLPFDGQNLKELRERVLRGkYRIP 219
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
247-482 3.19e-23

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: 99.27  E-value: 3.19e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIK---TLKEGTMSPEAFLGEaNVMkaLQHERLVRLYAVVTKE-----PIYIVTEYMARG 318
Cdd:cd14056   3 IGKGRYGEVWLGKYRGE-KVAVKifsSRDEDSWFRETEIYQ-TVM--LRHENILGFIAADIKStgswtQLWLITEYHEHG 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEgsrLSLPRLIDMSAQIAEGMAYIErmNSI----------HRDLRAANILVSEALCCKIADFGLA------ 382
Cdd:cd14056  79 SLYDYLQRNT---LDTEEALRLAYSAASGLAHLH--TEIvgtqgkpaiaHRDLKSKNILVKRDGTCCIADLGLAvrydsd 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 -RIIDSEYTAQEGAKfpiKWTAPE----AIHFGVFT--IKADVWSFGVLLMEV----VTYG-----RVPYPGM--SNPEV 444
Cdd:cd14056 154 tNTIDIPPNPRVGTK---RYMAPEvlddSINPKSFEsfKMADIYSFGLVLWEIarrcEIGGiaeeyQLPYFGMvpSDPSF 230
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 33469982 445 --IRNL--ERGYRMPRPD--TCPPEL--YRGVIAECWRSRPEERPT 482
Cdd:cd14056 231 eeMRKVvcVEKLRPPIPNrwKSDPVLrsMVKLMQECWSENPHARLT 276
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
244-482 4.54e-23

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: 98.27  E-value: 4.54e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPE---AFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARG 318
Cdd:cd08220   5 IRVVGRGAYGTVYLCRRKDDNKlVIIKQIPVEQMTKEerqAALNEVKVLSMLHHPNIIEYYeSFLEDKALMIVMEYAPGG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA-LCCKIADFGLARIIDSEYTAQEGAKF 397
Cdd:cd08220  85 TLFEYIQQRKGSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKKrTVVKIGDFGISKILSSKSKAYTVVGT 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 398 PIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVpYPGMSNPEVIRNLERGYRMPRPDTCPPELyRGVIAECWRSRP 477
Cdd:cd08220 165 PC-YISPELCEGKPYNQKSDIWALGCVLYELASLKRA-FEAANLPALVLKIMRGTFAPISDRYSEEL-RHLILSMLHLDP 241

                ....*
gi 33469982 478 EERPT 482
Cdd:cd08220 242 NKRPT 246
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
238-484 4.67e-23

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: 98.10  E-value: 4.67e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 238 RQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFL----GEANVMKALQHERLVRLYAVV-TKEPIYIVT 312
Cdd:cd14161   2 KHRYEFLETLGKGTYGRVKKARDSSGRLVAIKSIRKDRIKDEQDLlhirREIEIMSSLNHPHIISVYEVFeNSSKIVIVM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ 392
Cdd:cd14161  82 EYASRGDLYDYIS--ERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDKFLQ 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKFPIkWTAPEAIHFGVFT-IKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNLERG-YRMP-RP-DTCppelyrGV 468
Cdd:cd14161 160 TYCGSPL-YASPEIVNGRPYIgPEVDSWSLGVLLY-ILVHGTMPFDGHDYKILVKQISSGaYREPtKPsDAC------GL 231
                       250
                ....*....|....*.
gi 33469982 469 IAECWRSRPEERPTFE 484
Cdd:cd14161 232 IRWLLMVNPERRATLE 247
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
62-112 6.57e-23

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. 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). However, Brk lacks the N-terminal myristoylation sites. 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, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 91.49  E-value: 6.57e-23
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGT-GDWWLARSLVTGREGYVPSNF 112
Cdd:cd11845   1 IYVALYDYEARTDDDLSFKKGDRLQILDDSdGDWWLARHLSTGKEGYIPSNY 52
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
247-488 9.30e-23

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: 97.33  E-value: 9.30e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLKEGTmSPEAFLGEANVMKALQHERLVRLYAVVTKePIYIVTEYMARGCLLDFLKT 326
Cdd:cd14068   2 LGDGGFGSVYRAVYRGE-DVAVKIFNKHT-SFRLLRQELVVLSHLHHPSLVALLAAGTA-PRMLVMELAPKGSLDALLQQ 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 327 DEGSrlsLPRLID--MSAQIAEGMAYIERMNSIHRDLRAANILV-----SEALCCKIADFGLAriidsEYTAQEGAKF-- 397
Cdd:cd14068  79 DNAS---LTRTLQhrIALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYGIA-----QYCCRMGIKTse 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 398 -PIKWTAPEAIHFGV-FTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRP----DTCPPELYRGVIAE 471
Cdd:cd14068 151 gTPGFRAPEVARGNViYNQQADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQGKLPDPvkeyGCAPWPGVEALIKD 230
                       250       260
                ....*....|....*....|.
gi 33469982 472 CWRSRPEERPT----FEFLQS 488
Cdd:cd14068 231 CLKENPQCRPTsaqvFDILNS 251
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
247-445 1.05e-22

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


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 97.60  E-value: 1.05e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNN---MKV--------AIKTLKEGTMSPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTEY 314
Cdd:cd06628   8 IGSGSFGSVYLGMNASSgelMAVkqvelpsvSAENKDRKKSMLDALQREIALLRELQHENIVQyLGSSSDANHLNIFLEY 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKTDEGSRLSLPRliDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID--SEYTAQ 392
Cdd:cd06628  88 VPGGSVATLLNNYGAFEESLVR--NFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEanSLSTKN 165
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 393 EGAKFPIK----WTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVI 445
Cdd:cd06628 166 NGARPSLQgsvfWMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFPDCTQMQAI 221
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
244-487 1.29e-22

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: 97.33  E-value: 1.29e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMKVAIKTLKE-----GTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMAR 317
Cdd:cd14206   2 LQEIGNGWFGKVILGEIFSDYTPAQVVVKElrvsaGPLEQRKFISEAQPYRSLQHPNILQCLGLCTETiPFLLIMEFCQL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTD---EGSRLSLP-----RLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE- 388
Cdd:cd14206  82 GDLKRYLRAQrkaDGMTPDLPtrdlrTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSHNNYKEd 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 -YTAQEGAKFPIKWTAPEAI--HFGVFTI-----KADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRM----PR 456
Cdd:cd14206 162 yYLTPDRLWIPLRWVAPELLdeLHGNLIVvdqskESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVVREQQMklakPR 241
                       250       260       270
                ....*....|....*....|....*....|.
gi 33469982 457 PDTCPPELYRGVIAECWRSrPEERPTFEFLQ 487
Cdd:cd14206 242 LKLPYADYWYEIMQSCWLP-PSQRPSVEELH 271
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
244-482 2.34e-22

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: 97.11  E-value: 2.34e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMKV-AIKTL--KEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP---IYIVTEYMAR 317
Cdd:cd06621   6 LSSLGEGAGGSVTKCRLRNTKTIfALKTIttDPNPDVQKQILRELEINKSCASPYIVKYYGAFLDEQdssIGIAMEYCEG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKT--DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYTAQEG 394
Cdd:cd06621  86 GSLDSIYKKvkKKGGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSgELVNSLAGTFTG 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEvVTYGRVPYP--GMSNPEVIRNLERGYRMPRPD--TCP------PEL 464
Cdd:cd06621 166 TSY---YMAPERIQGGPYSITSDVWSLGLTLLE-VAQNRFPFPpeGEPPLGPIELLSYIVNMPNPElkDEPengikwSES 241
                       250
                ....*....|....*...
gi 33469982 465 YRGVIAECWRSRPEERPT 482
Cdd:cd06621 242 FKDFIEKCLEKDGTRRPG 259
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
237-482 2.40e-22

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: 96.68  E-value: 2.40e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKT--LKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVT 312
Cdd:cd06641   2 PEELFTKLEKIGKGSFGEVFKGIdNRTQKVVAIKIidLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDtKLWIIM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLktdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYTA 391
Cdd:cd06641  82 EYLGGGSALDLL---EPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAgQLTDTQIKR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIrnlergYRMPRPDtcPPEL------- 464
Cdd:cd06641 159 N*FVGTPF-WMAPEVIKQSAYDSKADIWSLGITAIELAR-GEPPHSELHPMKVL------FLIPKNN--PPTLegnyskp 228
                       250
                ....*....|....*...
gi 33469982 465 YRGVIAECWRSRPEERPT 482
Cdd:cd06641 229 LKEFVEACLNKEPSFRPT 246
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
243-456 2.73e-22

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: 95.93  E-value: 2.73e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMG-YYKNNMKVAIKTL------KEGTMspEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEY 314
Cdd:cd14663   4 LGRTLGEGTFAKVKFArNTKTGESVAIKIIdkeqvaREGMV--EQIKREIAIMKLLRHPNIVELHEVMaTKTKIFFVMEL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIidSEYTAQEG 394
Cdd:cd14663  82 VTGGEL--FSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSAL--SEQFRQDG 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 395 AKFPI----KWTAPEAI-HFGVFTIKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNLERG-YRMPR 456
Cdd:cd14663 158 LLHTTcgtpNYVAPEVLaRRGYDGAKADIWSCGVILF-VLLAGYLPFDDENLMALYRKIMKGeFEYPR 224
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
245-487 2.97e-22

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: 96.22  E-value: 2.97e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPEAFL---GEANVMKALQHERLVRLYAV-VTKEPIYIVTEYMARGC 319
Cdd:cd06626   6 NKIGEGTFGKVYTAVNLDTGELmAMKEIRFQDNDPKTIKeiaDEMKVLEGLDHPNLVRYYGVeVHREEVYIFMEYCQEGT 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKF-- 397
Cdd:cd06626  86 LEELLR--HGRILDEAVIRVYTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLKNNTTTMAPGEVns 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 398 ----PIkWTAPEAI-------HFGVftikADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRnlergYR--MPRPDTCPPEL 464
Cdd:cd06626 164 lvgtPA-YMAPEVItgnkgegHGRA----ADIWSLGCVVLEMAT-GKRPWSELDNEWAIM-----YHvgMGHKPPIPDSL 232
                       250       260
                ....*....|....*....|....*...
gi 33469982 465 Y-----RGVIAECWRSRPEERPTFEFLQ 487
Cdd:cd06626 233 QlspegKDFLSRCLESDPKKRPTASELL 260
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
243-441 3.09e-22

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: 97.60  E-value: 3.09e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYK-NNMKVAIKTLkegtmsPEAF---------LGEANVMKALQHERLVRLYAVVTKEP----- 307
Cdd:cd07834   4 LLKPIGSGAYGVVCSAYDKrTGRKVAIKKI------SNVFddlidakriLREIKILRHLKHENIIGLLDILRPPSpeefn 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 -IYIVTEYMArgclldflkTDegsrlsLPRLIDMS------------AQIAEGMAYIERMNSIHRDLRAANILVSEALCC 374
Cdd:cd07834  78 dVYIVTELME---------TD------LHKVIKSPqpltddhiqyflYQILRGLKYLHSAGVIHRDLKPSNILVNSNCDL 142
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 375 KIADFGLARIIDSEYTAQEgakfpikWT---------APEAI-HFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSN 441
Cdd:cd07834 143 KICDFGLARGVDPDEDKGF-------LTeyvvtrwyrAPELLlSSKKYTKAIDIWSVGCIFAELLT-RKPLFPGRDY 211
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
245-455 3.31e-22

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: 95.92  E-value: 3.31e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGC 319
Cdd:cd14071   6 RTIGKGNFAVVKLARHRiTKTEVAIKIIDKSQLDEenlKKIYREVQIMKMLNHPHIIKLYQVMeTKDMLYLVTEYASNGE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPi 399
Cdd:cd14071  86 IFDYLAQHG--RMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKPGELLKTWCGSP- 162
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 33469982 400 KWTAPEaihfgVFTIKA------DVWSFGVLLMeVVTYGRVPYPGMSNPEV-IRNLERGYRMP 455
Cdd:cd14071 163 PYAAPE-----VFEGKEyegpqlDIWSLGVVLY-VLVCGALPFDGSTLQTLrDRVLSGRFRIP 219
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
246-482 6.89e-22

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: 95.46  E-value: 6.89e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKN-NMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGcL 320
Cdd:cd07833   8 VVGEGAYGVVLKCRNKAtGEIVAIKKFKeseDDEDVKKTALREVKVLRQLRHENIVNLKeAFRRKGRLYLVFEYVERT-L 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLktdEGSRLSLPRLIDMSA--QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS-------EYTA 391
Cdd:cd07833  87 LELL---EASPGGLPPDAVRSYiwQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTArpaspltDYVA 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QegakfpiKW-TAPE----AIHFGVftiKADVWSFGVLLMEVVTyGRVPYPGMSN------------PEVIRNLERGYRM 454
Cdd:cd07833 164 T-------RWyRAPEllvgDTNYGK---PVDVWAIGCIMAELLD-GEPLFPGDSDidqlyliqkclgPLPPSHQELFSSN 232
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 33469982 455 PR------PDTCPPE----LYRGVIAE--------CWRSRPEERPT 482
Cdd:cd07833 233 PRfagvafPEPSQPEslerRYPGKVSSpaldflkaCLRMDPKERLT 278
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
242-486 7.14e-22

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: 95.09  E-value: 7.14e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGY-YKNNMKVAIKTL------KEGTMSPEAFLGEANVMKALQHERLVRLYAVV---TKEPIYIV 311
Cdd:cd06653   5 RLGKLLGRGAFGEVYLCYdADTGRELAVKQVpfdpdsQETSKEVNALECEIQLLKNLRHDRIVQYYGCLrdpEEKKLSIF 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSRLSLPRliDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd06653  85 VEYMPGGSVKDQLKAYGALTENVTR--RYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQTICMS 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIK---WTAPEAIHFGVFTIKADVWSFGVLLMEVVTygrvPYPGMSNPEVIRNLERGYRMPrpdtCPPELYRGV 468
Cdd:cd06653 163 GTGIKSVTGtpyWMSPEVISGEGYGRKADVWSVACTVVEMLT----EKPPWAEYEAMAAIFKIATQP----TKPQLPDGV 234
                       250       260
                ....*....|....*....|....*..
gi 33469982 469 IAEC---------WRSRpeeRPTFEFL 486
Cdd:cd06653 235 SDACrdflrqifvEEKR---RPTAEFL 258
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
242-482 8.77e-22

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: 94.80  E-value: 8.77e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMgyyKNNMKVA----IKTLKE---GTMSPEAFLG---EANVMKALQHERLVRLYA-VVTKEPIYI 310
Cdd:cd08222   3 RVVRKLGSGNFGTVYL---VSDLKATadeeLKVLKEisvGELQPDETVDanrEAKLLSKLDHPAIVKFHDsFVEKESFCI 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKT--DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALcCKIADFGLARII--- 385
Cdd:cd08222  80 VTEYCEGGDLDDKISEykKSGTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFLKNNV-IKVGDFGISRILmgt 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 DSEYTAQEGAKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELy 465
Cdd:cd08222 159 SDLATTFTGTPY---YMSPEVLKHEGYNSKSDIWSLGCILYEMCCL-KHAFDGQNLLSVMYKIVEGETPSLPDKYSKEL- 233
                       250
                ....*....|....*..
gi 33469982 466 RGVIAECWRSRPEERPT 482
Cdd:cd08222 234 NAIYSRMLNKDPALRPS 250
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
244-490 9.00e-22

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: 94.93  E-value: 9.00e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMG-YYKNN--MKVAIKTLKEGTMSPEA--FLGEANVMKALQHERLVR-LYAVVTKEPIYIVTEYMAR 317
Cdd:cd05086   2 IQEIGNGWFGKVLLGeIYTGTsvARVVVKELKASANPKEQddFLQQGEPYYILQHPNILQcVGQCVEAIPYLLVFEFCDL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDE------GSRLSLPRlidMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGL--ARIIDSEY 389
Cdd:cd05086  82 GDLKTYLANQQeklrgdSQIMLLQR---MACEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIgfSRYKEDYI 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQEGAKFPIKWTAPEAI---HFGVFTIK----ADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNL--ERGYRMPRPDTC 460
Cdd:cd05086 159 ETDDKKYAPLRWTAPELVtsfQDGLLAAEqtkySNIWSLGVTLWELFENAAQPYSDLSDREVLNHVikERQVKLFKPHLE 238
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 461 PP--ELYRGVIAECWRSrPEERPTFEFLQSVL 490
Cdd:cd05086 239 QPysDRWYEVLQFCWLS-PEKRPTAEEVHRLL 269
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
239-486 1.11e-21

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 94.30  E-value: 1.11e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVwmgyYK-----NNMKVAIKTlkegtmSPEAFLGEA----------NVMKALQHERLVRLY-AV 302
Cdd:cd14050   1 QCFTILSKLGEGSFGEV----FKvrsreDGKLYAVKR------SRSRFRGEKdrkrkleeveRHEKLGEHPNCVRFIkAW 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 303 VTKEPIYIVTEyMARGCLLDFLktDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd14050  71 EEKGILYIQTE-LCDTSLQQYC--EETHSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGLV 147
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSE--YTAQEGAKfpiKWTAPEAIHfGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSnPEVIRNlerGYrMPRPDT- 459
Cdd:cd14050 148 VELDKEdiHDAQEGDP---RYMAPELLQ-GSFTKAADIFSLGITILELACNLELPSGGDG-WHQLRQ---GY-LPEEFTa 218
                       250       260
                ....*....|....*....|....*...
gi 33469982 460 -CPPELyRGVIAECWRSRPEERPTFEFL 486
Cdd:cd14050 219 gLSPEL-RSIIKLMMDPDPERRPTAEDL 245
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
247-488 1.35e-21

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: 94.37  E-value: 1.35e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTL------------KEGTMSpEAFLGEANVMKALQHERLVRLYAVVTKEPIY-IVT 312
Cdd:cd06629   9 IGKGTYGRVYLAMNATTGEMlAVKQVelpktssdradsRQKTVV-DALKSEIDTLKDLDHPNIVQYLGFEETEDYFsIFL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARG----CLLDFLKTDEgsrlSLPRLIdmSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE 388
Cdd:cd06629  88 EYVPGGsigsCLRKYGKFEE----DLVRFF--TRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISKKSDDI 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGA--KFPIKWTAPEAIH---FGvFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIrnLERGYRMPRPDTcPPE 463
Cdd:cd06629 162 YGNNGATsmQGSVFWMAPEVIHsqgQG-YSAKVDIWSLGCVVLEMLA-GRRPWSDDEAIAAM--FKLGNKRSAPPV-PED 236
                       250       260       270
                ....*....|....*....|....*....|
gi 33469982 464 LYRGVIA-----ECWRSRPEERPTFEFLQS 488
Cdd:cd06629 237 VNLSPEAldflnACFAIDPRDRPTAAELLS 266
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
243-482 1.40e-21

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: 94.25  E-value: 1.40e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYK-NNMKVAIKTL---KEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMAR 317
Cdd:cd08225   4 IIKKIGEGSFGKIYLAKAKsDSEHCVIKEIdltKMPVKEKEASKKEVILLAKMKHPNIVTFFASFQENgRLFIVMEYCDG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSE-ALCCKIADFGLARII-DSEYTAQEGA 395
Cdd:cd08225  84 GDLMKRINRQRGVLFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKnGMVAKLGDFGIARQLnDSMELAYTCV 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELyRGVIAECWRS 475
Cdd:cd08225 164 GTPY-YLSPEICQNRPYNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGYFAPISPNFSRDL-RSLISQLFKV 240

                ....*..
gi 33469982 476 RPEERPT 482
Cdd:cd08225 241 SPRDRPS 247
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
237-482 1.61e-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: 94.35  E-value: 1.61e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMG---YYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVT 312
Cdd:cd06642   2 PEELFTKLERIGKGSFGEVYKGidnRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKgTKLWIIM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTdegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYTA 391
Cdd:cd06642  82 EYLGGGSALDLLKP---GPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAgQLTDTQIKR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLergyrmprPDTCPPEL------- 464
Cdd:cd06642 159 NTFVGTPF-WMAPEVIKQSAYDFKADIWSLGITAIELAK-GEPPNSDLHPMRVLFLI--------PKNSPPTLegqhskp 228
                       250
                ....*....|....*...
gi 33469982 465 YRGVIAECWRSRPEERPT 482
Cdd:cd06642 229 FKEFVEACLNKDPRFRPT 246
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
234-481 1.98e-21

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: 95.49  E-value: 1.98e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLvRKLGSGQFGEVWMGY-YKNNMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLYAVVTK---- 305
Cdd:cd07877  13 WEVPERYQNL-SPVGSGAYGSVCAAFdTKTGLRVAVKKLSrpfQSIIHAKRTYRELRLLKHMKHENVIGLLDVFTParsl 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 ---EPIYIVTEYMARgcllDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd07877  92 eefNDVYLVTHLMGA----DLNNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLA 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSEYTAQEGAKFpikWTAPE-AIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPrpdtcP 461
Cdd:cd07877 168 RHTDDEMTGYVATRW---YRAPEiMLNWMHYNQTVDIWSVGCIMAELLT-GRTLFPGTDHIDQLKLILRLVGTP-----G 238
                       250       260
                ....*....|....*....|
gi 33469982 462 PELYRGVIAECWRSRPEERP 481
Cdd:cd07877 239 AELLKKISSESARNYIQSLT 258
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
250-430 2.13e-21

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: 94.32  E-value: 2.13e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 250 GQFGEVWMGYYKNNMkVAIKTLKEgtMSPEAFLGEANVMK--ALQHERLVRLYAV----VTKEPIY-IVTEYMARGCLLD 322
Cdd:cd14053   6 GRFGAVWKAQYLNRL-VAVKIFPL--QEKQSWLTEREIYSlpGMKHENILQFIGAekhgESLEAEYwLITEFHERGSLCD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLKTDEgsrLSLPRLIDMSAQIAEGMAYI--ERMNS--------IHRDLRAANILVSEALCCKIADFGLARIID-----S 387
Cdd:cd14053  83 YLKGNV---ISWNELCKIAESMARGLAYLheDIPATngghkpsiAHRDFKSKNVLLKSDLTACIADFGLALKFEpgkscG 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 33469982 388 EYTAQEGAKfpiKWTAPE----AIHFGVFTIKA-DVWSFGVLLMEVVT 430
Cdd:cd14053 160 DTHGQVGTR---RYMAPEvlegAINFTRDAFLRiDMYAMGLVLWELLS 204
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
242-455 2.21e-21

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


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 93.49  E-value: 2.21e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEAFLG----EANVMKALQHERLVRLYAVV-TKEPIYIVTEYM 315
Cdd:cd14079   5 ILGKTLGVGSFGKVKLAEHElTGHKVAVKILNRQKIKSLDMEEkirrEIQILKLFRHPHIIRLYEVIeTPTDIFMVMEYV 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII-DSEYTaQEG 394
Cdd:cd14079  85 SGGELFDYIV--QKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLSNIMrDGEFL-KTS 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 33469982 395 AKFPiKWTAPEAIHFGVFT-IKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNLERG-YRMP 455
Cdd:cd14079 162 CGSP-NYAAPEVISGKLYAgPEVDVWSCGVILY-ALLCGSLPFDDEHIPNLFKKIKSGiYTIP 222
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
247-488 2.23e-21

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: 93.48  E-value: 2.23e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVwmgyyKNNM------KVAIKTLKEgtmspeAFL-----GEANV------MKALQHERLVRLYAVVT---KE 306
Cdd:cd14119   1 LGEGSYGKV-----KEVLdtetlcRRAVKILKK------RKLrripnGEANVkreiqiLRRLNHRNVIKLVDVLYneeKQ 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 PIYIVTEYmARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID 386
Cdd:cd14119  70 KLYMVMEY-CVGGLQEMLDSAPDKRLPIWQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAEALD 148
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 ---SEYTAQEGAKFPiKWTAPEAIHF-GVFT-IKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG-YRMprPDTC 460
Cdd:cd14119 149 lfaEDDTCTTSQGSP-AFQPPEIANGqDSFSgFKVDIWSAGVTLYNMTT-GKYPFEGDNIYKLFENIGKGeYTI--PDDV 224
                       250       260
                ....*....|....*....|....*...
gi 33469982 461 PPELyRGVIAECWRSRPEERPTFEFLQS 488
Cdd:cd14119 225 DPDL-QDLLRGMLEKDPEKRFTIEQIRQ 251
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
247-451 2.61e-21

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


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 93.06  E-value: 2.61e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVwmgyYK-----NNMKVAIKTLKegTMSP---EAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMAR 317
Cdd:cd14103   1 LGRGKFGTV----YRcvekaTGKELAAKFIK--CRKAkdrEDVRNEIEIMNQLRHPRLLQLYdAFETPREMVLVMEYVAG 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILvsealcC--------KIADFGLARIIDSEY 389
Cdd:cd14103  75 GELFERV-VDDDFELTERDCILFMRQICEGVQYMHKQGILHLDLKPENIL------CvsrtgnqiKIIDFGLARKYDPDK 147
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 390 TAQEGAKFPiKWTAPEAIHFGVFTIKADVWSFGvllmeVVTY----GRVPYPGMSNPEVIRNLERG 451
Cdd:cd14103 148 KLKVLFGTP-EFVAPEVVNYEPISYATDMWSVG-----VICYvllsGLSPFMGDNDAETLANVTRA 207
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
233-446 2.90e-21

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: 93.53  E-value: 2.90e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLrlvrkLGSGQFGEVWMGYY--KNNMKVAIKTLKEGTMSPEAFL--GEANVMKALQHERLVRLYAVV-TKEP 307
Cdd:cd14201   5 DFEYSRKDL-----VGHGAFAVVFKGRHrkKTDWEVAIKSINKKNLSKSQILlgKEIKILKELQHENIVALYDVQeMPNS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTdEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA---------LCCKIAD 378
Cdd:cd14201  80 VFLVMEYCNGGDLADYLQA-KGT-LSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSYAsrkkssvsgIRIKIAD 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 379 FGLARIIDSEYTAQEGAKFPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSnPEVIR 446
Cdd:cd14201 158 FGFARYLQSNMMAATLCGSPM-YMAPEVIMSQHYDAKADLWSIGTVIYQCLV-GKPPFQANS-PQDLR 222
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
237-482 4.25e-21

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: 93.19  E-value: 4.25e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKT--LKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTK-EPIYIVT 312
Cdd:cd06640   2 PEELFTKLERIGKGSFGEVFKGIdNRTQQVVAIKIidLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKgTKLWIIM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEGSRLslpRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYTA 391
Cdd:cd06640  82 EYLGGGSALDLLRAGPFDEF---QIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAgQLTDTQIKR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLergyrmprPDTCPPEL------- 464
Cdd:cd06640 159 NTFVGTPF-WMAPEVIQQSAYDSKADIWSLGITAIELAK-GEPPNSDMHPMRVLFLI--------PKNNPPTLvgdfskp 228
                       250
                ....*....|....*...
gi 33469982 465 YRGVIAECWRSRPEERPT 482
Cdd:cd06640 229 FKEFIDACLNKDPSFRPT 246
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
243-484 7.70e-21

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: 91.84  E-value: 7.70e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPE---AFL-GEANVMKALQHERLVRLYAV--VTKEPIYIVTEYM 315
Cdd:cd14164   4 LGTTIGEGSFSKVKLATsQKYCCKVAIKIVDRRRASPDfvqKFLpRELSILRRVNHPNIVQMFECieVANGRLYIVMEAA 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLdflKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVS-EALCCKIADFGLARIIDSEYTAQEG 394
Cdd:cd14164  84 ATDLLQ---KIQEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLSaDDRKIKIADFGFARFVEDYPELSTT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPIKWTAPEAI-HFGVFTIKADVWSFGVLLMEVVTyGRVPYPGmSNPEVIRNLERGYRMPRpDTCPPELYRGVIAECW 473
Cdd:cd14164 161 FCGSRAYTPPEVIlGTPYDPKKYDVWSLGVVLYVMVT-GTMPFDE-TNVRRLRLQQRGVLYPS-GVALEEPCRALIRTLL 237
                       250
                ....*....|.
gi 33469982 474 RSRPEERPTFE 484
Cdd:cd14164 238 QFNPSTRPSIQ 248
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
247-451 9.45e-21

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: 91.90  E-value: 9.45e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTL-KEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd14190  12 LGGGKFGKVHTCTEKrTGLKLAAKVInKQNSKDKEMVLLEIQVMNQLNHRNLIQLYeAIETPNEIVLFMEYVEGGELFER 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC--CKIADFGLARiidsEYTAQEGAKFPI-- 399
Cdd:cd14190  92 I-VDEDYHLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCVNRTGhqVKIIDFGLAR----RYNPREKLKVNFgt 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 400 -KWTAPEAIHFGVFTIKADVWSFGvllmeVVTY----GRVPYPGMSNPEVIRNLERG 451
Cdd:cd14190 167 pEFLSPEVVNYDQVSFPTDMWSMG-----VITYmllsGLSPFLGDDDTETLNNVLMG 218
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
247-448 1.04e-20

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: 91.51  E-value: 1.04e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNN-MKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd14193  12 LGGGRFGQVHKCEEKSSgLKLAAKIIKaRSQKEKEEVKNEIEVMNQLNHANLIQLYdAFESRNDIVLVMEYVDGGELFDR 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV--SEALCCKIADFGLARiidsEYTAQEGAKFPI-- 399
Cdd:cd14193  92 I-IDENYNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCvsREANQVKIIDFGLAR----RYKPREKLRVNFgt 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 400 -KWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNL 448
Cdd:cd14193 167 pEFLAPEVVNYEFVSFPTDMWSLGVIAYMLLS-GLSPFLGEDDNETLNNI 215
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
247-456 1.35e-20

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: 91.29  E-value: 1.35e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTlkegtMSPEAfLG--------EANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd14078  11 IGSGGFAKVKLATHIlTGEKVAIKI-----MDKKA-LGddlprvktEIEALKNLSHQHICRLYHVIeTDNKIFMVLEYCP 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA----RIIDSEYTAQ 392
Cdd:cd14078  85 GGELFDYIVAKD--RLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLCakpkGGMDHHLETC 162
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 393 EGAKfpiKWTAPEAI----HFGVftiKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG-YRMPR 456
Cdd:cd14078 163 CGSP---AYAAPELIqgkpYIGS---EADVWSMGVLLYALLC-GFLPFDDDNVMALYRKIQSGkYEEPE 224
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
258-490 1.44e-20

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: 91.46  E-value: 1.44e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 258 GYYkNNMKVAIKTLKEGTMS-PEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCLLDFLKTDE-----GS 330
Cdd:cd14045  26 GIY-DGRTVAIKKIAKKSFTlSKRIRKEVKQVRELDHPNLCKFIGGCIEVPnVAIITEYCPKGSLNDVLLNEDiplnwGF 104
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 331 RLSLprlidmSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGA---KFPIKWTAPEAI 407
Cdd:cd14045 105 RFSF------ATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLTTYRKEDGSENASGyqqRLMQVYLPPENH 178
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 408 HFGVF--TIKADVWSFGVLLMEVVTYGRVPypgmsnPEVIRNLERGYRMPRPD--------TCP-PELYRGVIAECWRSR 476
Cdd:cd14045 179 SNTDTepTQATDVYSYAIILLEIATRNDPV------PEDDYSLDEAWCPPLPElisgktenSCPcPADYVELIRRCRKNN 252
                       250
                ....*....|....
gi 33469982 477 PEERPTFEFLQSVL 490
Cdd:cd14045 253 PAQRPTFEQIKKTL 266
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
123-205 1.51e-20

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: 85.59  E-value: 1.51e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 123 RWFFRSQGRKEAERQLLApiNKAGSFLIRESETNKGAFSLSVKdvtTQGELIKHYKIRCLDEGGYYI-SPRITFPSLQAL 201
Cdd:cd00173   1 PWFHGSISREEAERLLRG--KPDGTFLVRESSSEPGDYVLSVR---SGDGKVKHYLIERNEGGYYLLgGSGRTFPSLPEL 75

                ....
gi 33469982 202 VQHY 205
Cdd:cd00173  76 VEHY 79
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
242-492 1.72e-20

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: 91.08  E-value: 1.72e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSP----EAFLGEANVMKALQHERLVRLYAVVT-KEPIYIVTEYM 315
Cdd:cd14099   4 RRGKFLGKGGFAKCYEVTdMSTGKVYAGKVVPKSSLTKpkqrEKLKSEIKIHRSLKHPNIVKFHDCFEdEENVYILLELC 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEytaqEGA 395
Cdd:cd14099  84 SNGSLMELLKRRK--ALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLEYD----GER 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPIKWT----APEAI-----HfgvfTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG-YRMPRPDTCPPELy 465
Cdd:cd14099 158 KKTLCGTpnyiAPEVLekkkgH----SFEVDIWSLGVILYTLLV-GKPPFETSDVKETYKRIKKNeYSFPSHLSISDEA- 231
                       250       260
                ....*....|....*....|....*..
gi 33469982 466 RGVIAECWRSRPEERPTfefLQSVLED 492
Cdd:cd14099 232 KDLIRSMLQPDPTKRPS---LDEILSH 255
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
242-438 1.98e-20

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 94.48  E-value: 1.98e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  242 RLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPEAFL----GEANVMKALQHERLVRLYAVVTKEPI-YIVTEYM 315
Cdd:NF033483  10 EIGERIGRGGMAEVYLAKdTRLDRDVAVKVLRPDLARDPEFVarfrREAQSAASLSHPNIVSVYDVGEDGGIpYIVMEYV 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  316 ArGCLL-DFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEG 394
Cdd:NF033483  90 D-GRTLkDYIR--EHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSTTMTQTN 166
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 33469982  395 AkfpIKWTA----PEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:NF033483 167 S---VLGTVhylsPEQARGGTVDARSDIYSLGIVLYEMLT-GRPPFDG 210
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
243-488 2.64e-20

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: 90.14  E-value: 2.64e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMAR 317
Cdd:cd08530   4 VLKKLGKGSYGSVYKVKRLSDNQVyALKEVNLGSLSQkerEDSVNEIRLLASVNHPNIIRYKeAFLDGNRLCIVMEYAPF 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSLPRLI--DMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYT-AQEG 394
Cdd:cd08530  84 GDLSKLISKRKKKRRLFPEDDiwRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKKNLAkTQIG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRgVIAECWR 474
Cdd:cd08530 164 TPL---YAAPEVWKGRPYDYKSDIWSLGCLLYEMAT-FRPPFEARTMQELRYKVCRGKFPPIPPVYSQDLQQ-IIRSLLQ 238
                       250
                ....*....|....*
gi 33469982 475 SRPEERPTF-EFLQS 488
Cdd:cd08530 239 VNPKKRPSCdKLLQS 253
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
246-484 3.07e-20

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: 90.04  E-value: 3.07e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMK--VAIKTLKEGTM---SPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGC 319
Cdd:cd14121   2 KLGSGTYATVYKAYRKSGARevVAVKCVSKSSLnkaSTENLLTEIELLKKLKHPHIVELKDFQwDEEHIYLIMEYCSGGD 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKtdegSRLSLPRLIDMS--AQIAEGMAYIERMNSIHRDLRAANILVSEAL--CCKIADFGLARII--DSEYTAQE 393
Cdd:cd14121  82 LSRFIR----SRRTLPESTVRRflQQLASALQFLREHNISHMDLKPQNLLLSSRYnpVLKLADFGFAQHLkpNDEAHSLR 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAkfPIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVtYGRVPYPGMSnpevIRNLERGYRMPRPDTCP--PELY---RGV 468
Cdd:cd14121 158 GS--PL-YMAPEMILKKKYDARVDLWSVGVILYECL-FGRAPFASRS----FEELEEKIRSSKPIEIPtrPELSadcRDL 229
                       250
                ....*....|....*.
gi 33469982 469 IAECWRSRPEERPTFE 484
Cdd:cd14121 230 LLRLLQRDPDRRISFE 245
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
239-486 3.51e-20

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: 90.58  E-value: 3.51e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEV-WMGYYKNNMKVAIKTLKEGTMSP--EAFLGEANVMKALQHERLVRLY-AVVTKEP-IYIVTE 313
Cdd:cd06620   5 QDLETLKDLGAGNGGSVsKVLHIPTGTIMAKKVIHIDAKSSvrKQILRELQILHECHSPYIVSFYgAFLNENNnIIICME 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSI-HRDLRAANILVSEALCCKIADFGLAR-IIDSEYTA 391
Cdd:cd06620  85 YMDCGSLDKILK--KKGPFPEEVLGKIAVAVLEGLTYLYNVHRIiHRDIKPSNILVNSKGQIKLCDFGVSGeLINSIADT 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY-------PGMSNPEVIRNL------ERGYRMPRPD 458
Cdd:cd06620 163 FVGTS---TYMSPERIQGGKYSVKSDVWSLGLSIIELAL-GEFPFagsndddDGYNGPMGILDLlqrivnEPPPRLPKDR 238
                       250       260
                ....*....|....*....|....*...
gi 33469982 459 TCPPELyRGVIAECWRSRPEERPTFEFL 486
Cdd:cd06620 239 IFPKDL-RDFVDRCLLKDPRERPSPQLL 265
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
234-481 6.09e-20

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: 90.88  E-value: 6.09e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLvRKLGSGQFGEVWMGY-YKNNMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLYAVVTK---- 305
Cdd:cd07878  11 WEVPERYQNL-TPVGSGAYGSVCSAYdTRLRQKVAVKKLSrpfQSLIHARRTYRELRLLKHMKHENVIGLLDVFTPatsi 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 ---EPIYIVTEYMARgcllDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd07878  90 enfNEVYLVTNLMGA----DLNNIVKCQKLSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLA 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSEYTAQEGAKFpikWTAPE-AIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGmsnPEVIRNLERgyRMPRPDTCP 461
Cdd:cd07878 166 RQADDEMTGYVATRW---YRAPEiMLNWMHYNQTVDIWSVGCIMAELLK-GKALFPG---NDYIDQLKR--IMEVVGTPS 236
                       250       260
                ....*....|....*....|
gi 33469982 462 PELYRGVIAECWRSRPEERP 481
Cdd:cd07878 237 PEVLKKISSEHARKYIQSLP 256
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
245-491 7.32e-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: 7.32e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKN-NMKVAIK---TLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVtKEPIYIVTEYMARGCL 320
Cdd:cd14025   2 EKVGSGGFGQVYKVRHKHwKTWLAIKcppSLHVDDSERMELLEEAKKMEMAKFRHILPVYGIC-SEPVGLVMEYMETGSL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTDEgsrLSLPRLIDMSAQIAEGMAYIERMNS--IHRDLRAANILVSEALCCKIADFGLAR---IIDSEYTAQEGA 395
Cdd:cd14025  81 EKLLASEP---LPWELRFRIIHETAVGMNFLHCMKPplLHLDLKPANILLDAHYHVKISDFGLAKwngLSHSHDLSRDGL 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPIKWTAPEAI--HFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSN-PEVIRNLERGYR---MPRPDTCPPELYRGV- 468
Cdd:cd14025 158 RGTIAYLPPERFkeKNRCPDTKHDVYSFAIVIWGILTQ-KKPFAGENNiLHIMVKVVKGHRpslSPIPRQRPSECQQMIc 236
                       250       260
                ....*....|....*....|....
gi 33469982 469 -IAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14025 237 lMKRCWDQDPRKRPTFQDITSETE 260
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
245-489 8.56e-20

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: 89.32  E-value: 8.56e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTM----SPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTEYMARG 318
Cdd:cd08228   8 KKIGRGQFSEVYRATcLLDRKPVALKKVQIFEMmdakARQDCVKEIDLLKQLNHPNVIKyLDSFIEDNELNIVLELADAG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEGSRLSLPR--LIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAK 396
Cdd:cd08228  88 DLSQMIKYFKKQKRLIPErtVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTAAHSLV 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 397 FPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPG--MSNPEVIRNLERGYRMPRPDTCPPELYRGVIAECWR 474
Cdd:cd08228 168 GTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAAL-QSPFYGdkMNLFSLCQKIEQCDYPPLPTEHYSEKLRELVSMCIY 246
                       250
                ....*....|....*
gi 33469982 475 SRPEERPTFEFLQSV 489
Cdd:cd08228 247 PDPDQRPDIGYVHQI 261
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
247-480 8.76e-20

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: 88.73  E-value: 8.76e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSP----EAFLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMARGCL 320
Cdd:cd05123   1 LGKGSFGKVLLVRKKDTGKLyAMKVLRKKEIIKrkevEHTLNERNILERVNHPFIVKLhYAFQTEEKLYLVLDYVPGGEL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKtDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAqegakfpiK 400
Cdd:cd05123  81 FSHLS-KEG-RFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSSDGDR--------T 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 WT--------APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRN-LERGYRMprPDTCPPELyRGVIAE 471
Cdd:cd05123 151 YTfcgtpeylAPEVLLGKGYGKAVDWWSLGVLLYEMLT-GKPPFYAENRKEIYEKiLKSPLKF--PEYVSPEA-KSLISG 226

                ....*....
gi 33469982 472 CWRSRPEER 480
Cdd:cd05123 227 LLQKDPTKR 235
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
244-483 1.08e-19

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: 89.21  E-value: 1.08e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMSPEA----FLGEANVMKALQHERLVRLYAVVTkEPIY--IVTEYMA 316
Cdd:cd14026   2 LRYLSRGAFGTVSRARHADwRVTVAIKCLKLDSPVGDSerncLLKEAEILHKARFSYILPILGICN-EPEFlgIVTEYMT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFL-KTDEGSRLSLPRLIDMSAQIAEGMAYIERMNS--IHRDLRAANILVSEALCCKIADFGLA--RIID----- 386
Cdd:cd14026  81 NGSLNELLhEKDIYPDVAWPLRLRILYEIALGVNYLHNMSPplLHHDLKTQNILLDGEFHVKIADFGLSkwRQLSisqsr 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SEYTAQEGAKfpIKWTAPEAIHFGVFT---IKADVWSFGVLLMEVVTYgRVPYPGMSNP-EVIRNLERGYRMPRPDTCPP 462
Cdd:cd14026 161 SSKSAPEGGT--IIYMPPEEYEPSQKRrasVKHDIYSYAIIMWEVLSR-KIPFEEVTNPlQIMYSVSQGHRPDTGEDSLP 237
                       250       260
                ....*....|....*....|....*..
gi 33469982 463 ------ELYRGVIAECWRSRPEERPTF 483
Cdd:cd14026 238 vdiphrATLINLIESGWAQNPDERPSF 264
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
242-430 1.14e-19

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: 88.56  E-value: 1.14e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPE------AFLGEANVMKALQHERLVRLYAVVTKEP---IYIV 311
Cdd:cd06652   5 RLGKLLGQGAFGRVYLCYdADTGRELAVKQVQFDPESPEtskevnALECEIQLLKNLLHERIVQYYGCLRDPQertLSIF 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSRLSLPRliDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd06652  85 MEYMPGGSIKDQLKSYGALTENVTR--KYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTICLS 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 33469982 392 QEGAKFPIK---WTAPEAIHFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd06652 163 GTGMKSVTGtpyWMSPEVISGEGYGRKADIWSVGCTVVEMLT 204
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
228-490 1.31e-19

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: 88.91  E-value: 1.31e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 228 PWAQDEWEIprqslrlVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEAFLGEANVMKALQ-HERLVRLYA---- 301
Cdd:cd06638  14 PDPSDTWEI-------IETIGKGTYGKVFKVLNKkNGSKAAVKILDPIHDIDEEIEAEYNILKALSdHPNVVKFYGmyyk 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 302 --VVTKEPIYIVTEYMARGCLLDFLK--TDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIA 377
Cdd:cd06638  87 kdVKNGDQLWLVLELCNGGSVTDLVKgfLKRGERMEEPIIAYILHEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLV 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 378 DFGL-ARIIDSEYTAQEGAKFPIkWTAPEAIHF-----GVFTIKADVWSFGVLLMEVVTYGrvpyPGMSNPEVIRNLERG 451
Cdd:cd06638 167 DFGVsAQLTSTRLRRNTSVGTPF-WMAPEVIACeqqldSTYDARCDVWSLGITAIELGDGD----PPLADLHPMRALFKI 241
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 33469982 452 YRMPRPDTCPPELYRG----VIAECWRSRPEERPTF-EFLQSVL 490
Cdd:cd06638 242 PRNPPPTLHQPELWSNefndFIRKCLTKDYEKRPTVsDLLQHVF 285
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
244-461 1.74e-19

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: 88.48  E-value: 1.74e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYK-NNMKVAIKTL----KEGTmsPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMAR 317
Cdd:cd07870   5 LEKLGEGSYATVYKGISRiNGQLVALKVIsmktEEGV--PFTAIREASLLKGLKHANIVLLHDIIhTKETLTFVFEYMHT 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GcLLDFLKTDEGSRLSLPRLIDMsAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI--IDSEYTAQEGA 395
Cdd:cd07870  83 D-LAQYMIQHPGGLHPYNVRLFM-FQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLARAksIPSQTYSSEVV 160
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 396 KFpikWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSN-PEVIRNLERGYRMPRPDTCP 461
Cdd:cd07870 161 TL---WYRPPDVLLGAtdYSSALDIWGAGCIFIEMLQ-GQPAFPGVSDvFEQLEKIWTVLGVPTEDTWP 225
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
242-430 1.74e-19

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: 88.63  E-value: 1.74e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKN--NMKVAIKTLKEGTMSP---EAFLGEANVMKALQ---HERLVRLYAVVTKEP-IYIVT 312
Cdd:cd14052   3 ANVELIGSGEFSQVYKVSERVptGKVYAVKKLKPNYAGAkdrLRRLEEVSILRELTldgHDNIVQLIDSWEYHGhLYIQT 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFL-KTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYT 390
Cdd:cd14052  83 ELCENGSLDVFLsELGLLGRLDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMAtVWPLIRGI 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 33469982 391 AQEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd14052 163 EREGDR---EYIAPEILSEHMYDKPADIFSLGLILLEAAA 199
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
242-440 1.82e-19

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: 88.91  E-value: 1.82e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMK-VAIKTL-----KEGTmsPEAFLGEANVMKALQHERLVRLYAVVTKEP-------- 307
Cdd:cd07866  11 EILGKLGEGTFGEVYKARQIKTGRvVALKKIlmhneKDGF--PITALREIKILKKLKHPNVVPLIDMAVERPdkskrkrg 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 -IYIVTEYMARGclLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID 386
Cdd:cd07866  89 sVYMVTPYMDHD--LSGLLENPSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPYD 166
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 387 SEYTAQEGAKFPIK----------W-TAPEAI-HFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMS 440
Cdd:cd07866 167 GPPPNPKGGGGGGTrkytnlvvtrWyRPPELLlGERRYTTAVDIWGIGCVFAEMFT-RRPILQGKS 231
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
246-461 1.94e-19

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: 88.59  E-value: 1.94e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYK-NNMKVAIKTLK----EGTmsPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARgc 319
Cdd:cd07844   7 KLGEGSYATVYKGRSKlTGQLVALKEIRleheEGA--PFTAIREASLLKDLKHANIVTLHDIIhTKKTLTLVFEYLDT-- 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 llDFLKTDEgsrlSLPRLIDMSA------QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiidseytaqe 393
Cdd:cd07844  83 --DLKQYMD----DCGGGLSMHNvrlflfQLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLAR---------- 146
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 gAK-FPIK---------WTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEviRNLERGYRM---PRPD 458
Cdd:cd07844 147 -AKsVPSKtysnevvtlWYRPPDVLLGSteYSTSLDMWGVGCIFYEMAT-GRPLFPGSTDVE--DQLHKIFRVlgtPTEE 222

                ...
gi 33469982 459 TCP 461
Cdd:cd07844 223 TWP 225
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
247-491 2.07e-19

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: 87.53  E-value: 2.07e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMARGCLLDFLK 325
Cdd:cd14155   1 IGSGFFSEVYKVRHRTSGQVMALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVCVHQgQLHALTEYINGGNLEQLLD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 326 TDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV---SEALCCKIADFGLA-RIIDSEYtaqEGAKFPI-- 399
Cdd:cd14155  81 SNE--PLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrdENGYTAVVGDFGLAeKIPDYSD---GKEKLAVvg 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 400 --KWTAPEAIHFGVFTIKADVWSFGVLLMEVVtyGRVPypgmSNPEVIRNLER------GYRMPRPDtCPPELYRGVIaE 471
Cdd:cd14155 156 spYWMAPEVLRGEPYNEKADVFSYGIILCEII--ARIQ----ADPDYLPRTEDfgldydAFQHMVGD-CPPDFLQLAF-N 227
                       250       260
                ....*....|....*....|
gi 33469982 472 CWRSRPEERPTFEFLQSVLE 491
Cdd:cd14155 228 CCNMDPKSRPSFHDIVKTLE 247
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
247-451 2.08e-19

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


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 87.32  E-value: 2.08e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYI-VTEYMARGCLLDFL 324
Cdd:cd14006   1 LGRGRFGVVKRCIEKATGReFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVlILELCSGGELLDRL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 325 KTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSE--ALCCKIADFGLARIIDseytaQEGAKFPIKWT 402
Cdd:cd14006  81 AERG--SLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLADrpSPQIKIIDFGLARKLN-----PGEELKEIFGT 153
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 403 ----APEAIHFGVFTIKADVWSFGVLlmevvTY----GRVPYPGMSNPEVIRNLERG 451
Cdd:cd14006 154 pefvAPEIVNGEPVSLATDMWSIGVL-----TYvllsGLSPFLGEDDQETLANISAC 205
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
243-482 2.34e-19

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: 87.75  E-value: 2.34e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMK-VAIKTLKegtMSP----EAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMA 316
Cdd:cd06613   4 LIQRIGSGTYGDVYKARNIATGElAAVKVIK---LEPgddfEIIQQEISMLKECRHPNIVAYFgSYLRRDKLWIVMEYCG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLD-FLKTDEgsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSeyTAQEGA 395
Cdd:cd06613  81 GGSLQDiYQVTGP---LSELQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSAQLTA--TIAKRK 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KF---PIkWTAPEAI---HFGVFTIKADVWSFGVLLMEVVTYgrvpYPGMSNPEVIRNLergYRMPRPDTCPPEL----- 464
Cdd:cd06613 156 SFigtPY-WMAPEVAaveRKGGYDGKCDIWALGITAIELAEL----QPPMFDLHPMRAL---FLIPKSNFDPPKLkdkek 227
                       250       260
                ....*....|....*....|..
gi 33469982 465 ----YRGVIAECWRSRPEERPT 482
Cdd:cd06613 228 wspdFHDFIKKCLTKNPKKRPT 249
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
234-438 2.72e-19

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: 88.89  E-value: 2.72e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQsLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPE----AFLgEANVMKALQHERLVRLYAVVTK--- 305
Cdd:cd07851  11 WEVPDR-YQNLSPVGSGAYGQVCSAFdTKTGRKVAIKKLSRPFQSAIhakrTYR-ELRLLKHMKHENVIGLLDVFTPass 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 ----EPIYIVTEYMARgcllDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGL 381
Cdd:cd07851  89 ledfQDVYLVTHLMGA----DLNNIVKCQKLSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGL 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 382 ARIIDSEYTAQEGAKFpikWTAPEAI-HFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd07851 165 ARHTDDEMTGYVATRW---YRAPEIMlNWMHYNQTVDIWSVGCIMAELLT-GKTLFPG 218
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
245-455 3.91e-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: 87.27  E-value: 3.91e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTL------KEGTMSpEAFLgEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMA 316
Cdd:cd05581   7 KPLGEGSYSTVVLAKEKeTGKEYAIKVLdkrhiiKEKKVK-YVTI-EKEVLSRLAHPGIVKLYYTFQDESkLYFVLEYAP 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDegSRLSLP--RLIdmSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEG 394
Cdd:cd05581  85 NGDLLEYIRKY--GSLDEKctRFY--TAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLGPDSSPEST 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPIKW-------------TA----PEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEV---IRNLErgYRM 454
Cdd:cd05581 161 KGDADSQiaynqaraasfvgTAeyvsPELLNEKPAGKSSDLWALGCIIYQMLT-GKPPFRGSNEYLTfqkIVKLE--YEF 237

                .
gi 33469982 455 P 455
Cdd:cd05581 238 P 238
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
248-482 4.14e-19

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: 87.49  E-value: 4.14e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 248 GSGQFGEVWMGYYKNNMkVAIKTLKEGtmSPEAFLGEANVMKA--LQHERLVRLYA-----VVTKEPIYIVTEYMARGCL 320
Cdd:cd13998   4 GKGRFGEVWKASLKNEP-VAVKIFSSR--DKQSWFREKEIYRTpmLKHENILQFIAaderdTALRTELWLVTAFHPNGSL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTdegSRLSLPRLIDMSAQIAEGMAYIER--------MNSI-HRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd13998  81 *DYLSL---HTIDWVSLCRLALSVARGLAHLHSeipgctqgKPAIaHRDLKSKNILVKNDGTCCIADFGLAVRLSPSTGE 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFP----IKWTAPE----AIHFGVFT--IKADVWSFGVLLMEV-----VTYGRVPYPGMSNPEVIRNLERGYRMP- 455
Cdd:cd13998 158 EDNANNGqvgtKRYMAPEvlegAINLRDFEsfKRVDIYAMGLVLWEMasrctDLFGIVEEYKPPFYSEVPNHPSFEDMQe 237
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 33469982 456 -------RPDTCP-----PELyRGV---IAECWRSRPEERPT 482
Cdd:cd13998 238 vvvrdkqRPNIPNrwlshPGL-QSLaetIEECWDHDAEARLT 278
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
243-436 4.42e-19

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: 87.37  E-value: 4.42e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMK-VAIKTLK-EGTMSPEA-------FLGEANVMKALQHERLVRLYAVVTKEPIYIVT- 312
Cdd:cd13990   4 LLNLLGKGGFSEVYKAFDLVEQRyVACKIHQlNKDWSEEKkqnyikhALREYEIHKSLDHPRIVKLYDVFEIDTDSFCTv 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 -EYMArGCLLDF-LKTDEGSRLSLPRLIDMsaQIAEGMAYierMNS-----IHRDLRAANILVSE---ALCCKIADFGLA 382
Cdd:cd13990  84 lEYCD-GNDLDFyLKQHKSIPEREARSIIM--QVVSALKY---LNEikppiIHYDLKPGNILLHSgnvSGEIKITDFGLS 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 383 RIIDS--------EYTAQEGAKFpikW-TAPEAIHFG----VFTIKADVWSFGVLLMEVVtYGRVPY 436
Cdd:cd13990 158 KIMDDesynsdgmELTSQGAGTY---WyLPPECFVVGktppKISSKVDVWSVGVIFYQML-YGRKPF 220
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
280-490 5.45e-19

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: 86.89  E-value: 5.45e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 280 AFLGEANVMKALQHERLVRLYAVVTKEPIYI-VTEYMARGCLLDFLKTDEGSRLSLPRLIdMSAQIAEGMAYIERMNSIH 358
Cdd:cd05076  61 AFFETASLMSQVSHTHLVFVHGVCVRGSENImVEEFVEHGPLDVWLRKEKGHVPMAWKFV-VARQLASALSYLENKNLVH 139
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 359 RDLRAANILVSE-------ALCCKIADFGLARIIDSEYTAQEgakfPIKWTAPEAIHFGV-FTIKADVWSFGVLLMEVVT 430
Cdd:cd05076 140 GNVCAKNILLARlgleegtSPFIKLSDPGVGLGVLSREERVE----RIPWIAPECVPGGNsLSTAADKWGFGATLLEICF 215
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 431 YGRVPYPGMSNPEVIRNLERGYRMPRPDTcpPELyRGVIAECWRSRPEERPTFEFLQSVL 490
Cdd:cd05076 216 NGEAPLQSRTPSEKERFYQRQHRLPEPSC--PEL-ATLISQCLTYEPTQRPSFRTILRDL 272
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
247-448 5.48e-19

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: 86.55  E-value: 5.48e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNN-MKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd14192  12 LGGGRFGQVHKCTELSTgLTLAAKIIKvKGAKEREEVKNEINIMNQLNHVNLIQLYdAFESKTNLTLIMEYVDGGELFDR 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV--SEALCCKIADFGLARiidsEYTAQEGAKFPI-- 399
Cdd:cd14192  92 I-TDESYQLTELDAILFTRQICEGVHYLHQHYILHLDLKPENILCvnSTGNQIKIIDFGLAR----RYKPREKLKVNFgt 166
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 400 -KWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNL 448
Cdd:cd14192 167 pEFLAPEVVNYDFVSFPTDMWSVGVITYMLLS-GLSPFLGETDAETMNNI 215
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
234-438 7.88e-19

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 87.70  E-value: 7.88e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPrQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSpEAFLGEA----NVMKALQHERLVRLYAVVTKE-- 306
Cdd:cd07880  11 WEVP-DRYRDLKQVGSGAYGTVCSALdRRTGAKVAIKKLYRPFQS-ELFAKRAyrelRLLKHMKHENVIGLLDVFTPDls 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 -----PIYIVTEYMARgcllDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGL 381
Cdd:cd07880  89 ldrfhDFYLVMPFMGT----DLGKLMKHEKLSEDRIQFLVYQMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGL 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 382 ARIIDSEYTAQEGAKFpikWTAPEAI-HFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd07880 165 ARQTDSEMTGYVVTRW---YRAPEVIlNWMHYTQTVDIWSVGCIMAEMLT-GKPLFKG 218
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
234-430 8.52e-19

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143384 [Multi-domain]  Cd Length: 342  Bit Score: 87.65  E-value: 8.52e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 234 WEIPRQSLRLvRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSpEAFLGEA----NVMKALQHERLVRLYAVVTKEPI 308
Cdd:cd07879  11 WELPERYTSL-KQVGSGAYGSVCSAIdKRTGEKVAIKKLSRPFQS-EIFAKRAyrelTLLKHMQHENVIGLLDVFTSAVS 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 -------YIVTEYMargcLLDFLKTdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGL 381
Cdd:cd07879  89 gdefqdfYLVMPYM----QTDLQKI-MGHPLSEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAVNEDCELKILDFGL 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 382 ARIIDSEYTAQEGAKFpikWTAPEAI-HFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd07879 164 ARHADAEMTGYVVTRW---YRAPEVIlNWMHYNQTVDIWSVGCIMAEMLT 210
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
266-490 1.20e-18

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: 85.71  E-value: 1.20e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 266 VAIKTLK--EGTMSPEAFLgEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCLLDFLKTD----EGSRLSLPRLI 338
Cdd:cd14044  34 VILKDLKnnEGNFTEKQKI-ELNKLLQIDYYNLTKFYGTVKLDTmIFGVIEYCERGSLRDVLNDKisypDGTFMDWEFKI 112
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 339 DMSAQIAEGMAYIERMN-SIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAqegakfpikWTAPEAIHFGVFTIKAD 417
Cdd:cd14044 113 SVMYDIAKGMSYLHSSKtEVHGRLKSTNCVVDSRMVVKITDFGCNSILPPSKDL---------WTAPEHLRQAGTSQKGD 183
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 418 VWSFGVLLMEVVTYGRVPYPGMSNPEVirnlERGYRMPRPDTCPP---------------ELYrGVIAECWRSRPEERPT 482
Cdd:cd14044 184 VYSYGIIAQEIILRKETFYTAACSDRK----EKIYRVQNPKGMKPfrpdlnlesagererEVY-GLVKNCWEEDPEKRPD 258

                ....*...
gi 33469982 483 FEFLQSVL 490
Cdd:cd14044 259 FKKIENTL 266
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
237-494 1.28e-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: 1.28e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMG-YYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY--AVVTKEP------ 307
Cdd:cd06636  14 PAGIFELVEVVGNGTYGQVYKGrHVKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYSHHRNIATYygAFIKKSPpghddq 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS 387
Cdd:cd06636  94 LWLVMEFCGAGSVTDLVKNTKGNALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYTAQEGAKFPIKWTAPEAIHF-----GVFTIKADVWSFGVLLMEVVTYGrvpyPGMSNPEVIRNLergYRMPRpdTCPP 462
Cdd:cd06636 174 TVGRRNTFIGTPYWMAPEVIACdenpdATYDYRSDIWSLGITAIEMAEGA----PPLCDMHPMRAL---FLIPR--NPPP 244
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 463 ELyrgviaecwRSRPEERPTFEFLQSVLEDFY 494
Cdd:cd06636 245 KL---------KSKKWSKKFIDFIEGCLVKNY 267
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
246-461 1.28e-18

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


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 86.23  E-value: 1.28e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYY-KNNMKVAIK-----TLKEGTmsPEAFLGEANVMKALQ-HERLVRLYAVVTK-EPIYIVTEYMAR 317
Cdd:cd07832   7 RIGEGAHGIVFKAKDrETGETVALKkvalrKLEGGI--PNQALREIKALQACQgHPYVVKLRDVFPHgTGFVLVFEYMLS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GcLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE----YTAQE 393
Cdd:cd07832  85 S-LSEVLR-DEERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEdprlYSHQV 162
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 394 GAKFpikWTAPEAIhFGV--FTIKADVWSFGVLLMEVVTygRVP-YPGMSNPE----VIRNLErgyrMPRPDTCP 461
Cdd:cd07832 163 ATRW---YRAPELL-YGSrkYDEGVDLWAVGCIFAELLN--GSPlFPGENDIEqlaiVLRTLG----TPNEKTWP 227
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
281-481 1.34e-18

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


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 85.79  E-value: 1.34e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 281 FLGEANVMKALQHERLVRLYAVvTKEPIYIVTEYMARGCLLDFL--KTDEGSRLSLPRLI--DMSAQIAEGMAYIERMNS 356
Cdd:cd14067  57 FRQEASMLHSLQHPCIVYLIGI-SIHPLCFALELAPLGSLNTVLeeNHKGSSFMPLGHMLtfKIAYQIAAGLAYLHKKNI 135
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 357 IHRDLRAANILV-----SEALCCKIADFGLARiiDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTy 431
Cdd:cd14067 136 IFCDLKSDNILVwsldvQEHINIKLSDYGISR--QSFHEGALGVEGTPGYQAPEIRPRIVYDEKVDMFSYGMVLYELLS- 212
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 432 GRVPYPGMSNPEVIRNLERGYrmpRPDTCPPE---LYR--GVIAECWRSRPEERP 481
Cdd:cd14067 213 GQRPSLGHHQLQIAKKLSKGI---RPVLGQPEevqFFRlqALMMECWDTKPEKRP 264
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
247-486 1.65e-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: 85.60  E-value: 1.65e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYY-KNNMKVAIKTLKEGTMSPE--------AFLGEanvMKALQHERLVRLYAVVTKEP-IYIVTEYMA 316
Cdd:cd06917   9 VGRGSYGAVYRGYHvKTGRVVALKVLNLDTDDDDvsdiqkevALLSQ---LKLGQPKNIIKYYGSYLKGPsLWIIMDYCE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKtdeGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAK 396
Cdd:cd06917  86 GGSIRTLMR---AGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSKRSTFV 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 397 FPIKWTAPEAIHFGV-FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIrnlergyrMPRPDTCPPEL--------YRG 467
Cdd:cd06917 163 GTPYWMAPEVITEGKyYDTKADIWSLGITTYEMAT-GNPPYSDVDALRAV--------MLIPKSKPPRLegngysplLKE 233
                       250
                ....*....|....*....
gi 33469982 468 VIAECWRSRPEERPTFEFL 486
Cdd:cd06917 234 FVAACLDEEPKDRLSADEL 252
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
246-477 1.66e-18

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: 85.83  E-value: 1.66e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYK--NNMkVAIKTLK----EGtmSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd07871  12 KLGEGTYATVFKGRSKltENL-VALKEIRleheEG--APCTAIREVSLLKNLKHANIVTLHDIIhTERCLTLVFEYLDSD 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 cLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiIDSEYTAQEGAKFP 398
Cdd:cd07871  89 -LKQYLD-NCGNLMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLAR-AKSVPTKTYSNEVV 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 IKWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCPP----ELYRGVIAEC 472
Cdd:cd07871 166 TLWYRPPDVLLGSteYSTPIDMWGVGCILYEMAT-GRPMFPGSTVKEELHLIFRLLGTPTEETWPGvtsnEEFRSYLFPQ 244

                ....*
gi 33469982 473 WRSRP 477
Cdd:cd07871 245 YRAQP 249
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
244-438 1.81e-18

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: 86.76  E-value: 1.81e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKN-NMKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLYAVV----------TKEP---- 307
Cdd:cd07854  10 LRPLGCGSNGLVFSAVDSDcDKRVAVKKIVlTDPQSVKHALREIKIIRRLDHDNIVKVYEVLgpsgsdltedVGSLteln 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 -IYIVTEYMARgcllDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVS-EALCCKIADFGLARII 385
Cdd:cd07854  90 sVYIVQEYMET----DLANVLEQGPLSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFINtEDLVLKIGDFGLARIV 165
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 386 DSEYTAQ----EGakFPIKW-TAPE-AIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd07854 166 DPHYSHKgylsEG--LVTKWyRSPRlLLSPNNYTKAIDMWAAGCIFAEMLT-GKPLFAG 221
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
247-447 1.87e-18

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: 85.01  E-value: 1.87e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGY-YKNNMKVAIKTLKEgtmSPEAF---LGEANVMKALQ------HERLVRLYAVVT-KEPIYIVTEyM 315
Cdd:cd14133   7 LGKGTFGQVVKCYdLLTGEEVALKIIKN---NKDYLdqsLDEIRLLELLNkkdkadKYHIVRLKDVFYfKNHLCIVFE-L 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCC--KIADFG--------LARII 385
Cdd:cd14133  83 LSQNLYEFLKQNKFQYLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLASYSRCqiKIIDFGsscfltqrLYSYI 162
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33469982 386 DSEYtaqegakfpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRN 447
Cdd:cd14133 163 QSRY-----------YRAPEVILGLPYDEKIDMWSLGCILAELYT-GEPLFPGASEVDQLAR 212
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
241-482 1.94e-18

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: 84.97  E-value: 1.94e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPEA---FLGEANVMKALQHERLVRLY----AVVTKEPIYIvT 312
Cdd:cd13983   3 LKFNEVLGRGSFKTVYRAFdTEEGIEVAWNEIKLRKLPKAErqrFKQEIEILKSLKHPNIIKFYdsweSKSKKEVIFI-T 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNS--IHRDLRAANILVSEAL-CCKIADFGLARIIDSEY 389
Cdd:cd13983  82 ELMTSGTLKQYLKRFK--RLKLKVIKSWCRQILEGLNYLHTRDPpiIHRDLKCDNIFINGNTgEVKIGDLGLATLLRQSF 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 taqegAKFPI---KWTAPEaIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNP-EVIRNLERGYrmpRPD----TCP 461
Cdd:cd13983 160 -----AKSVIgtpEFMAPE-MYEEHYDEKVDIYAFGMCLLEMAT-GEYPYSECTNAaQIYKKVTSGI---KPEslskVKD 229
                       250       260
                ....*....|....*....|.
gi 33469982 462 PELYRgVIAECWRSrPEERPT 482
Cdd:cd13983 230 PELKD-FIEKCLKP-PDERPS 248
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
120-219 2.12e-18

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: 80.12  E-value: 2.12e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAERQLLAPINkaGSFLIRESETNKGAFSLSVKdvttQGELIKHYKIRCLDEGGYYISPRITFPSLQ 199
Cdd:cd09935   1 EKHSWYHGPISRNAAEYLLSSGIN--GSFLVRESESSPGQYSISLR----YDGRVYHYRISEDSDGKVYVTQEHRFNTLA 74
                        90       100
                ....*....|....*....|
gi 33469982 200 ALVQHYSKKGDGLCQRLTLP 219
Cdd:cd09935  75 ELVHHHSKNADGLITTLRYP 94
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
246-488 2.22e-18

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


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 84.96  E-value: 2.22e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMKVAIK--TLKEGTMSP-EAFLGEANVMKALQHE-RLVRLY-AVVTKEP--IYIVTEY---- 314
Cdd:cd14131   8 QLGKGGSSKVYKVLNPKKKIYALKrvDLEGADEQTlQSYKNEIELLKKLKGSdRIIQLYdYEVTDEDdyLYMVMECgeid 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARgclldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAAN-ILVSEALccKIADFGLARIIDSEYT--- 390
Cdd:cd14131  88 LAT-----ILKKKRPKPIDPNFIRYYWKQMLEAVHTIHEEGIVHSDLKPANfLLVKGRL--KLIDFGIAKAIQNDTTsiv 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 391 --AQEGAkfpIKWTAPEAI------HFGVFTIK----ADVWSFGVLLMEVVtYGRVPYPGMSNPevIRNLER----GYRM 454
Cdd:cd14131 161 rdSQVGT---LNYMSPEAIkdtsasGEGKPKSKigrpSDVWSLGCILYQMV-YGKTPFQHITNP--IAKLQAiidpNHEI 234
                       250       260       270
                ....*....|....*....|....*....|....
gi 33469982 455 PRPDTCPPELYRgVIAECWRSRPEERPTFEFLQS 488
Cdd:cd14131 235 EFPDIPNPDLID-VMKRCLQRDPKKRPSIPELLN 267
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
244-483 2.43e-18

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: 85.25  E-value: 2.43e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMS---PEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd07860   5 VEKIGEGTYGVVYKARNKLTGEvVALKKIRLDTETegvPSTAIREISLLKELNHPNIVKLLDVIhTENKLYLVFEFLHQD 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 cLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFP 398
Cdd:cd07860  85 -LKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVT 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 IKWTAPEaIHFG--VFTIKADVWSFGVLLMEVVTYgRVPYPGMSNpevIRNLERGYRM---PRPDTCPpelyrGVIaecw 473
Cdd:cd07860 164 LWYRAPE-ILLGckYYSTAVDIWSLGCIFAEMVTR-RALFPGDSE---IDQLFRIFRTlgtPDEVVWP-----GVT---- 229
                       250
                ....*....|
gi 33469982 474 rSRPEERPTF 483
Cdd:cd07860 230 -SMPDYKPSF 238
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
245-486 2.48e-18

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: 84.81  E-value: 2.48e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTLK-EGTMSPEAF---LGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYmarg 318
Cdd:cd06607   7 REIGHGSFGAVYYARNKrTSEVVAIKKMSySGKQSTEKWqdiIKEVKFLRQLRHPNTIEYKGCYLREhTAWLVMEY---- 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEGSRLSLpRLIDMSA---QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSeytAQEGA 395
Cdd:cd06607  83 CLGSASDIVEVHKKPL-QEVEIAAichGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLVCP---ANSFV 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPIkWTAPE---AIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIrnlergYRMPRPDtcPPEL-------- 464
Cdd:cd06607 159 GTPY-WMAPEvilAMDEGQYDGKVDVWSLGITCIELAER-KPPLFNMNAMSAL------YHIAQND--SPTLssgewsdd 228
                       250       260
                ....*....|....*....|..
gi 33469982 465 YRGVIAECWRSRPEERPTFEFL 486
Cdd:cd06607 229 FRNFVDSCLQKIPQDRPSAEDL 250
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
245-482 2.48e-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: 84.63  E-value: 2.48e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTM----SPEAFLGEANVMKALQHERLVRLYA--VVTKEpIYIVTEYMAR 317
Cdd:cd08224   6 KKIGKGQFSVVYRARCLlDGRLVALKKVQIFEMmdakARQDCLKEIDLLQQLNHPNIIKYLAsfIENNE-LNIVLELADA 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSLP-RLI-DMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE-- 393
Cdd:cd08224  85 GDLSRLIKHFKKQKRLIPeRTIwKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKTTAAHsl 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 -GAKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPY--PGMSNPEVIRNLERGYRMPRPDTCPPELYRGVIA 470
Cdd:cd08224 165 vGTPY---YMSPERIREQGYDFKSDIWSLGCLLYEMAAL-QSPFygEKMNLYSLCKKIEKCEYPPLPADLYSQELRDLVA 240
                       250
                ....*....|..
gi 33469982 471 ECWRSRPEERPT 482
Cdd:cd08224 241 ACIQPDPEKRPD 252
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
246-461 2.63e-18

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: 85.44  E-value: 2.63e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYK--NNMkVAIKTLK----EGtmSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd07873   9 KLGEGTYATVYKGRSKltDNL-VALKEIRleheEG--APCTAIREVSLLKDLKHANIVTLHDIIhTEKSLTLVFEYLDKD 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 cLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiIDSEYTAQEGAKFP 398
Cdd:cd07873  86 -LKQYLD-DCGNSINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR-AKSIPTKTYSNEVV 162
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 399 IKWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCP 461
Cdd:cd07873 163 TLWYRPPDILLGStdYSTQIDMWGVGCIFYEMST-GRPLFPGSTVEEQLHFIFRILGTPTEETWP 226
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
287-484 2.81e-18

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: 84.77  E-value: 2.81e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 287 VMKALQHERlVRLY--AVVTKEPIYIVTEYMARGCLLDFLKTDEGS-----RLSLprLIDMsaqiAEGMAYIERMNSIHR 359
Cdd:cd14043  49 KLRELRHEN-VNLFlgLFVDCGILAIVSEHCSRGSLEDLLRNDDMKldwmfKSSL--LLDL----IKGMRYLHHRGIVHG 121
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 360 DLRAANILVSEALCCKIADFGLARIIDSE-YTAQEGAKFPIKWTAPEAIHFGVF----TIKADVWSFGVLLMEVVTYGrV 434
Cdd:cd14043 122 RLKSRNCVVDGRFVLKITDYGYNEILEAQnLPLPEPAPEELLWTAPELLRDPRLerrgTFPGDVFSFAIIMQEVIVRG-A 200
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 435 PYP--GMSNPEVIRNLERGYRMPRP----DTCPPELYRgVIAECWRSRPEERPTFE 484
Cdd:cd14043 201 PYCmlGLSPEEIIEKVRSPPPLCRPsvsmDQAPLECIQ-LMKQCWSEAPERRPTFD 255
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
289-488 3.09e-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: 84.33  E-value: 3.09e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 289 KALQHERLVRLYAVVTKEP-------IYIVTEYMARGCLLDFLktDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDL 361
Cdd:cd14012  53 KKLRHPNLVSYLAFSIERRgrsdgwkVYLLTEYAPGGSLSELL--DSVGSVPLDTARRWTLQLLEALEYLHRNGVVHKSL 130
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 362 RAANILVSEALC---CKIADFGLARIIDSEYTAQ-EGAKFPIKWTAPEAIHFGV-FTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd14012 131 HAGNVLLDRDAGtgiVKLTDYSLGKTLLDMCSRGsLDEFKQTYWLPPELAQGSKsPTRKTDVWDLGLLFLQMLF-GLDVL 209
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 33469982 437 PGMSNPEVIRNlergyrmprPDTCPPELyRGVIAECWRSRPEERPT-FEFLQS 488
Cdd:cd14012 210 EKYTSPNPVLV---------SLDLSASL-QDFLSKCLSLDPKKRPTaLELLPH 252
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
245-482 3.10e-18

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: 85.09  E-value: 3.10e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNmKVAIK---TLKEGTMSPEAFLGEANVMKalqHERLVRLYAVVTK-----EPIYIVTEYMA 316
Cdd:cd14220   1 RQIGKGRYGEVWMGKWRGE-KVAVKvffTTEEASWFRETEIYQTVLMR---HENILGFIAADIKgtgswTQLYLITDYHE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTdegSRLSLPRLIDMSAQIAEGMAYIE--------RMNSIHRDLRAANILVSEALCCKIADFGLA------ 382
Cdd:cd14220  77 NGSLYDFLKC---TTLDTRALLKLAYSAACGLCHLHteiygtqgKPAIAHRDLKSKNILIKKNGTCCIADLGLAvkfnsd 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 -RIIDSEYTAQEGAKfpiKWTAPEAI-------HFGVFtIKADVWSFGVLLMEV----VTYG-----RVPYPGM--SNP- 442
Cdd:cd14220 154 tNEVDVPLNTRVGTK---RYMAPEVLdeslnknHFQAY-IMADIYSFGLIIWEMarrcVTGGiveeyQLPYYDMvpSDPs 229
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 33469982 443 -EVIRNLERGYRMpRP--------DTCPPELYRgVIAECWRSRPEERPT 482
Cdd:cd14220 230 yEDMREVVCVKRL-RPtvsnrwnsDECLRAVLK-LMSECWAHNPASRLT 276
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
237-504 3.35e-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: 85.16  E-value: 3.35e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMG-YYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY--AVVTKEP------ 307
Cdd:cd06637   4 PAGIFELVELVGNGTYGQVYKGrHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKYSHHRNIATYygAFIKKNPpgmddq 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS 387
Cdd:cd06637  84 LWLVMEFCGAGSVTDLIKNTKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYTAQEGAKFPIKWTAPEAIHF-----GVFTIKADVWSFGVLLMEVVTYGrvpyPGMSNPEVIRNLERGYRMPRPDTCPP 462
Cdd:cd06637 164 TVGRRNTFIGTPYWMAPEVIACdenpdATYDFKSDLWSLGITAIEMAEGA----PPLCDMHPMRALFLIPRNPAPRLKSK 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 33469982 463 EL---YRGVIAECWRSRPEERPTFEFL--QSVLEDfyTATERQYELQ 504
Cdd:cd06637 240 KWskkFQSFIESCLVKNHSQRPSTEQLmkHPFIRD--QPNERQVRIQ 284
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
245-484 4.34e-18

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


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 84.20  E-value: 4.34e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNMKV-AIKTLKE---GTMSPEAFLGEANVMKALQHE-RLVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd14198  14 KELGRGKFAVVRQCISKSTGQEyAAKFLKKrrrGQDCRAEILHEIAVLELAKSNpRVVNLHEVYeTTSEIILILEYAAGG 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC---CKIADFGLARIIDSEYTAQEGA 395
Cdd:cd14198  94 EIFNLCVPDLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPlgdIKIVDFGMSRKIGHACELREIM 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCP--PELYRGVIAECW 473
Cdd:cd14198 174 GTP-EYLAPEILNYDPITTATDMWNIGVIAYMLLT-HESPFVGEDNQETFLNISQVNVDYSEETFSsvSQLATDFIQKLL 251
                       250
                ....*....|.
gi 33469982 474 RSRPEERPTFE 484
Cdd:cd14198 252 VKNPEKRPTAE 262
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
242-438 6.20e-18

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: 85.05  E-value: 6.20e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYK-NNMKVAIKTLK--EGTMSPEAFLGEANVMKALQHERLVRLYAVV------TKEPIYIVT 312
Cdd:cd07849   8 QNLSYIGEGAYGMVCSAVHKpTGQKVAIKKISpfEHQTYCLRTLREIKILLRFKHENIIGILDIQrpptfeSFKDVYIVQ 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARgcllDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS----- 387
Cdd:cd07849  88 ELMET----DLYKLIKTQHLSNDHIQYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLARIADPehdht 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 388 ----EYTAQegakfpiKW-TAPE-AIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd07849 164 gfltEYVAT-------RWyRAPEiMLNSKGYTKAIDIWSVGCILAEMLS-NRPLFPG 212
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
247-488 6.86e-18

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: 83.96  E-value: 6.86e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVwmgyyknnMKV---------AIK--TLKEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEY 314
Cdd:cd14046  14 LGKGAFGQV--------VKVrnkldgryyAIKkiKLRSESKNNSRILREVMLLSRLNHQHVVRYYqAWIERANLYIQMEY 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFlkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiidSEYTAQEG 394
Cdd:cd14046  86 CEKSTLRDL--IDSGLFQDTDRLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLAT---SNKLNVEL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPIK---------------------WTAPE--AIHFGVFTIKADVWSFGVLLMEVVTYgrvPYPGMSNPEVIRNLeRG 451
Cdd:cd14046 161 ATQDINkstsaalgssgdltgnvgtalYVAPEvqSGTKSTYNEKVDMYSLGIIFFEMCYP---FSTGMERVQILTAL-RS 236
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 33469982 452 YRMPRPDTCPPELY---RGVIAECWRSRPEERPT-FEFLQS 488
Cdd:cd14046 237 VSIEFPPDFDDNKHskqAKLIRWLLNHDPAKRPSaQELLKS 277
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
247-430 6.90e-18

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: 83.59  E-value: 6.90e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPE------AFLGEANVMKALQHERLVRLYAVV---TKEPIYIVTEYMA 316
Cdd:cd06651  15 LGQGAFGRVYLCYdVDTGRELAAKQVQFDPESPEtskevsALECEIQLLKNLQHERIVQYYGCLrdrAEKTLTIFMEYMP 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGSRLSLPRliDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAK 396
Cdd:cd06651  95 GGSVKDQLKAYGALTESVTR--KYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTICMSGTGIR 172
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 33469982 397 FPIK---WTAPEAIHFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd06651 173 SVTGtpyWMSPEVISGEGYGRKADVWSLGCTVVEMLT 209
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
247-492 8.65e-18

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: 83.13  E-value: 8.65e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKN---NMKVAIKTL--KEGTMSPEAF----LGEANVMKALQHERLVRLYAVVTKEP--IYIVTEYM 315
Cdd:cd13994   1 IGKGATSVVRIVTKKNprsGVLYAVKEYrrRDDESKRKDYvkrlTSEYIISSKLHHPNIVKVLDLCQDLHgkWCLVMEYC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII----DSEYTA 391
Cdd:cd13994  81 PGGDLFTLIEKAD--SLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAEVFgmpaEKESPM 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKA-DVWSFGVLLMEVVTyGRVPY--PGMSNPEvIRNLERGYRMPRPDTCPPELYRGV 468
Cdd:cd13994 159 SAGLCGSEPYMAPEVFTSGSYDGRAvDVWSCGIVLFALFT-GRFPWrsAKKSDSA-YKAYEKSGDFTNGPYEPIENLLPS 236
                       250       260
                ....*....|....*....|....*....
gi 33469982 469 IAECWRSR-----PEERPTfefLQSVLED 492
Cdd:cd13994 237 ECRRLIYRmlhpdPEKRIT---IDEALND 262
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
237-487 9.98e-18

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: 82.88  E-value: 9.98e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTE 313
Cdd:cd06648   5 PRSDLDNFVKIGEGSTGIVCIATdKSTGRQVAVKKMDlRKQQRRELLFNEVVIMRDYQHPNIVEMYsSYLVGDELWVVME 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTdegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE 393
Cdd:cd06648  85 FLEGGALTDIVTH---TRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKEVPRRK 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLeRGYRMPR---PDTCPPELyRGVIA 470
Cdd:cd06648 162 SLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVD-GEPPYFNEPPLQAMKRI-RDNEPPKlknLHKVSPRL-RSFLD 238
                       250
                ....*....|....*...
gi 33469982 471 ECWRSRPEERPT-FEFLQ 487
Cdd:cd06648 239 RMLVRDPAQRATaAELLN 256
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
225-497 1.06e-17

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: 83.54  E-value: 1.06e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 225 PQNPWAQDEWEIPRQSLRLVRKLGSGQFGEVWMG-YYKNNMKVAIKTLK----EGTMSPEAFLGEANVMKALQHERLVRL 299
Cdd:cd08229  10 PQKALRPDMGYNTLANFRIEKKIGRGQFSEVYRAtCLLDGVPVALKKVQifdlMDAKARADCIKEIDLLKQLNHPNVIKY 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 300 YAVVTKE-PIYIVTEYMARGCLLDFLKTDEGSRLSLPR--LIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKI 376
Cdd:cd08229  90 YASFIEDnELNIVLELADAGDLSRMIKHFKKQKRLIPEktVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKL 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 377 ADFGLARIIDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPG--MSNPEVIRNLERGYRM 454
Cdd:cd08229 170 GDLGLGRFFSSKTTAAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAAL-QSPFYGdkMNLYSLCKKIEQCDYP 248
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 33469982 455 PRPDTCPPELYRGVIAECWRSRPEERPTFEFLQSVLEDFYTAT 497
Cdd:cd08229 249 PLPSDHYSEELRQLVNMCINPDPEKRPDITYVYDVAKRMHART 291
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
243-486 1.09e-17

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


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 83.12  E-value: 1.09e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYY-KNNMKVAIKTLKEGTMSPEAFLGEANVMKAL-QHERLVRLYAVVTKEP-------IYIVTE 313
Cdd:cd06608  10 LVEVIGEGTYGKVYKARHkKTGQLAAIKIMDIIEDEEEEIKLEINILRKFsNHPNIATFYGAFIKKDppggddqLWLVME 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKT--DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd06608  90 YCGGGSVTDLVKGlrKKGKRLKEEWIAYILRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSAQLDSTLGR 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QE---GAKFpikWTAPEAIHF-----GVFTIKADVWSFGVLLMEVVTyGRVPYPGMsNPevIRNLERGYRMPRPDTCPPE 463
Cdd:cd06608 170 RNtfiGTPY---WMAPEVIACdqqpdASYDARCDVWSLGITAIELAD-GKPPLCDM-HP--MRALFKIPRNPPPTLKSPE 242
                       250       260
                ....*....|....*....|....*..
gi 33469982 464 L----YRGVIAECWRSRPEERPTFEFL 486
Cdd:cd06608 243 KwskeFNDFISECLIKNYEQRPFTEEL 269
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
285-484 1.20e-17

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: 82.78  E-value: 1.20e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 285 ANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCLLDFLktDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRA 363
Cdd:cd14106  59 AVLELCKDCPRVVNLHEVYeTRSELILILELAAGGELQTLL--DEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKP 136
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 364 ANILVSEALCC---KIADFGLARIIDSEYTAQEGAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMS 440
Cdd:cd14106 137 QNILLTSEFPLgdiKLCDFGISRVIGEGEEIREILGTP-DYVAPEILSYEPISLATDMWSIGVLTYVLLT-GHSPFGGDD 214
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 33469982 441 NPEVIRNLERGYRmprpdTCPPELYRGV-------IAECWRSRPEERPTFE 484
Cdd:cd14106 215 KQETFLNISQCNL-----DFPEELFKDVsplaidfIKRLLVKDPEKRLTAK 260
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
242-492 1.59e-17

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: 82.73  E-value: 1.59e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMKV-AIKTL----KEGTmspEAFLGEANVMKALQHERLVRL--YAVVTKEP----IYI 310
Cdd:cd13986   3 RIQRLLGEGGFSFVYLVEDLSTGRLyALKKIlchsKEDV---KEAMREIENYRLFNHPNILRLldSQIVKEAGgkkeVYL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKT--DEGSRLSLPRLIDMSAQIAEGMAYIERMNSI---HRDLRAANILVSEALCCKIADFG---LA 382
Cdd:cd13986  80 LLPYYKRGSLQDEIERrlVKGTFFPEDRILHIFLGICRGLKAMHEPELVpyaHRDIKPGNVLLSEDDEPILMDLGsmnPA 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RI-IDSEYTAQEGAKF-----PIKWTAPEAIHF---GVFTIKADVWSFGVLLMEVVtYGRVPYpgmsnpEVIrnLERG-- 451
Cdd:cd13986 160 RIeIEGRREALALQDWaaehcTMPYRAPELFDVkshCTIDEKTDIWSLGCTLYALM-YGESPF------ERI--FQKGds 230
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 452 ---------YRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd13986 231 lalavlsgnYSFPDNSRYSEELHQ-LVKSMLVVNPAERPSIDDLLSRVHD 279
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
240-487 1.76e-17

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: 82.86  E-value: 1.76e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVW-MGYYKNNMKVAIKTLKEGTMSPE--AFLGEANV-MKALQHERLVRLYAVVTKE-PIYIVTEY 314
Cdd:cd06617   2 DLEVIEELGRGAYGVVDkMRHVPTGTIMAVKRIRATVNSQEqkRLLMDLDIsMRSVDCPYTVTFYGALFREgDVWICMEV 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARgCLLDFLKT--DEGSRLSLPRLIDMSAQIAEGMAYI-ERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDS-EY 389
Cdd:cd06617  82 MDT-SLDKFYKKvyDKGLTIPEDILGKIAVSIVKALEYLhSKLSVIHRDVKPSNVLINRNGQVKLCDFGISgYLVDSvAK 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQEGAKfpiKWTAPEAI----HFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNP-EVIRNLERGyrmPRP----DTC 460
Cdd:cd06617 161 TIDAGCK---PYMAPERInpelNQKGYDVKSDVWSLGITMIELAT-GRFPYDSWKTPfQQLKQVVEE---PSPqlpaEKF 233
                       250       260
                ....*....|....*....|....*..
gi 33469982 461 PPELyRGVIAECWRSRPEERPTFEFLQ 487
Cdd:cd06617 234 SPEF-QDFVNKCLKKNYKERPNYPELL 259
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
247-494 1.77e-17

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: 81.98  E-value: 1.77e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVW-MGYYKNNMKVAIKTLKEGTMSP----EAFLGEANVMKALQHERLVRLYAVVT-KEPIYIVTEYMARGCL 320
Cdd:cd14188   9 LGKGGFAKCYeMTDLTTNKVYAAKIIPHSRVSKphqrEKIDKEIELHRILHHKHVVQFYHYFEdKENIYILLEYCSRRSM 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGL-ARIIDSEYTAQEGAKFPi 399
Cdd:cd14188  89 AHILKARK--VLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLaARLEPLEHRRRTICGTP- 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 400 KWTAPEAIHFGVFTIKADVWSFGVlLMEVVTYGRVPYPGMSNPEVIRNL-ERGYRMPRPDTCPPelyRGVIAECWRSRPE 478
Cdd:cd14188 166 NYLSPEVLNKQGHGCESDIWALGC-VMYTMLLGRPPFETTNLKETYRCIrEARYSLPSSLLAPA---KHLIASMLSKNPE 241
                       250
                ....*....|....*.
gi 33469982 479 ERPTFEFLqsVLEDFY 494
Cdd:cd14188 242 DRPSLDEI--IRHDFF 255
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
227-482 1.98e-17

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: 82.48  E-value: 1.98e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 227 NPwaQDEWEIprqslrlVRKLGSGQFGEVWMGYYKN-NMKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLYAVVT 304
Cdd:cd06611   2 NP--NDIWEI-------IGELGDGAFGKVYKAQHKEtGLFAAAKIIQiESEEELEDFMVEIDILSECKHPNIVGLYEAYF 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 305 KEP-IYIVTEYMARGCLLDF-LKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd06611  73 YENkLWILIEFCDGGALDSImLELERG--LTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVS 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSeyTAQEGAKF---PiKWTAPEAIHFGVFT-----IKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIrnlergYRM 454
Cdd:cd06611 151 AKNKS--TLQKRDTFigtP-YWMAPEVVACETFKdnpydYKADIWSLGITLIELAQ-MEPPHHELNPMRVL------LKI 220
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 33469982 455 PRPDtcPPEL---------YRGVIAECWRSRPEERPT 482
Cdd:cd06611 221 LKSE--PPTLdqpskwsssFNDFLKSCLVKDPDDRPT 255
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
246-491 1.99e-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: 81.77  E-value: 1.99e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNmKVAIKTLKEGTMSPEA---FLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCLL 321
Cdd:cd14057   2 KINETHSGELWKGRWQGN-DIVAKILKVRDVTTRIsrdFNEEYPRLRIFSHPNVLPVLGACNSPPnLVVISQYMPYGSLY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSI--HRDLRAANILVSEALCCKIAdfglarIIDSEYTAQEGAK-FP 398
Cdd:cd14057  81 NVLHEGTGVVVDQSQAVKFALDIARGMAFLHTLEPLipRHHLNSKHVMIDEDMTARIN------MADVKFSFQEPGKmYN 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 IKWTAPEAIHFGVFTIK---ADVWSFGVLLMEVVTYgRVPYPGMSNPEV-IRNLERGYRMPRPDTCPPELYRgVIAECWR 474
Cdd:cd14057 155 PAWMAPEALQKKPEDINrrsADMWSFAILLWELVTR-EVPFADLSNMEIgMKIALEGLRVTIPPGISPHMCK-LMKICMN 232
                       250
                ....*....|....*..
gi 33469982 475 SRPEERPTFEFLQSVLE 491
Cdd:cd14057 233 EDPGKRPKFDMIVPILE 249
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
247-465 2.56e-17

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 82.89  E-value: 2.56e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  247 LGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPEAF---------------LGEANVMKALQHERLVRLYAV-VTKEPIY 309
Cdd:PTZ00024  17 LGEGTYGKVEKAYDTLTGKiVAIKKVKIIEISNDVTkdrqlvgmcgihfttLRELKIMNEIKHENIMGLVDVyVEGDFIN 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  310 IVTEYMARgcllDFLKT-DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR----- 383
Cdd:PTZ00024  97 LVMDIMAS----DLKKVvDRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLARrygyp 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  384 IIDSEYTAQEGAKFPIKWT---------APEAIhFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSNpevIRNLERGY 452
Cdd:PTZ00024 173 PYSDTLSKDETMQRREEMTskvvtlwyrAPELL-MGAekYHFAVDMWSVGCIFAELLT-GKPLFPGENE---IDQLGRIF 247
                        250
                 ....*....|....*.
gi 33469982  453 RM---PRPDTCPPELY 465
Cdd:PTZ00024 248 ELlgtPNEDNWPQAKK 263
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
228-455 2.92e-17

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 85.17  E-value: 2.92e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   228 PWAQDEWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMK------VAIKTLKEGTMSpeAFLGEANVMKALQHERLVRL-- 299
Cdd:PTZ00266    2 PGKYDDGESRLNEYEVIKKIGNGRFGEVFLVKHKRTQEffcwkaISYRGLKEREKS--QLVIEVNVMRELKHKNIVRYid 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   300 -YAVVTKEPIYIVTEYMARG--------CLLDFLKTDEGSrlslprLIDMSAQIAEGMAYIERMNS-------IHRDLRA 363
Cdd:PTZ00266   80 rFLNKANQKLYILMEFCDAGdlsrniqkCYKMFGKIEEHA------IVDITRQLLHALAYCHNLKDgpngervLHRDLKP 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982   364 ANILVSEAL-----------------CCKIADFGLARIIDSEYTAQEGAKFPIKWTAPEAIH-FGVFTIKADVWSFGVLL 425
Cdd:PTZ00266  154 QNIFLSTGIrhigkitaqannlngrpIAKIGDFGLSKNIGIESMAHSCVGTPYYWSPELLLHeTKSYDDKSDMWALGCII 233
                         250       260       270
                  ....*....|....*....|....*....|.
gi 33469982   426 MEVVTyGRVPYPGMSN-PEVIRNLERGYRMP 455
Cdd:PTZ00266  234 YELCS-GKTPFHKANNfSQLISELKRGPDLP 263
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
242-441 3.16e-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: 81.53  E-value: 3.16e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMKV-AIKTL-KEGTMSPEA---FLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYM 315
Cdd:cd05578   3 QILRVIGKGSFGKVCIVQKKDTKKMfAMKYMnKQKCIEKDSvrnVLNELEILQELEHPFLVNLwYSFQDEEDMYMVVDLL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLldflktdegsRLSLPRLIDMS--------AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS 387
Cdd:cd05578  83 LGGDL----------RYHLQQKVKFSeetvkfyiCEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTD 152
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 33469982 388 EYTAQEGAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVtYGRVPYPGMSN 441
Cdd:cd05578 153 GTLATSTSGTK-PYMAPEVFMRAGYSFAVDWWSLGVTAYEML-RGKRPYEIHSR 204
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
243-457 3.71e-17

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: 82.66  E-value: 3.71e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTM----SPEAFLGEANVMK-ALQHERLVRLYAVV-TKEPIYIVTEYM 315
Cdd:cd05619   9 LHKMLGKGSFGKVFLAELKgTNQFFAIKALKKDVVlmddDVECTMVEKRVLSlAWEHPFLTHLFCTFqTKENLFFVMEYL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKTdeGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR---IIDSEYTAQ 392
Cdd:cd05619  89 NGGDLMFHIQS--CHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKenmLGDAKTSTF 166
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 393 EGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLergyRMPRP 457
Cdd:cd05619 167 CGTP---DYIAPEILLGQKYNTSVDWWSFGVLLYEMLI-GQSPFHGQDEEELFQSI----RMDNP 223
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
247-481 3.86e-17

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: 81.39  E-value: 3.86e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK--VAIK-----------TLKEGTMSPEAFLGEANVMK-ALQHERLVRLYAVVTKEP-IYIV 311
Cdd:cd08528   8 LGSGAFGCVYKVRKKSNGQtlLALKeinmtnpafgrTEQERDKSVGDIISEVNIIKeQLRHPNIVRYYKTFLENDrLYIV 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEyMARGC----LLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSI-HRDLRAANILVSEALCCKIADFGLARIID 386
Cdd:cd08528  88 ME-LIEGAplgeHFSSLK-EKNEHFTEDRIWNIFVQMVLALRYLHKEKQIvHRDLKPNNIMLGEDDKVTITDFGLAKQKG 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRmPRPDTCPPELYR 466
Cdd:cd08528 166 PESSKMTSVVGTILYSCPEIVQNEPYGEKADIWALGCILYQMCTLQPPFYSTNMLTLATKIVEAEYE-PLPEGMYSDDIT 244
                       250
                ....*....|....*
gi 33469982 467 GVIAECWRSRPEERP 481
Cdd:cd08528 245 FVIRSCLTPDPEARP 259
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
240-461 3.88e-17

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: 82.05  E-value: 3.88e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWMGYYKNNMK-VAIKT--LKEGTMSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYM 315
Cdd:cd07869   6 SYEKLEKLGEGSYATVYKGKSKVNGKlVALKVirLQEEEGTPFTAIREASLLKGLKHANIVLLHDIIhTKETLTLVFEYV 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGcLLDFLKTDEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI--IDSEYTAQE 393
Cdd:cd07869  86 HTD-LCQYMDKHPGG-LHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLARAksVPSHTYSNE 163
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 33469982 394 GAKFpikWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSnpEVIRNLERGYRM---PRPDTCP 461
Cdd:cd07869 164 VVTL---WYRPPDVLLGSteYSTCLDMWGVGCIFVEMIQ-GVAAFPGMK--DIQDQLERIFLVlgtPNEDTWP 230
SH3_Lyn cd12004
Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of ...
63-117 3.89e-17

Src homology 3 domain of Lyn Protein Tyrosine Kinase; 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212937 [Multi-domain]  Cd Length: 56  Bit Score: 75.42  E-value: 3.89e-17
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982  63 VVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVARVE 117
Cdd:cd12004   2 VVALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARSLTTKKEGFIPSNYVAKVN 56
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
247-455 4.07e-17

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: 82.02  E-value: 4.07e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLKEGtmSPEAFLGEANVMKA--LQHERLVRLYAVVTKEPI------YIVTEYMARG 318
Cdd:cd14054   3 IGQGRYGTVWKGSLDER-PVAVKVFPAR--HRQNFQNEKDIYELplMEHSNILRFIGADERPTAdgrmeyLLVLEYAPKG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEGSRLSLPRlidMSAQIAEGMAYI---ERMNSI------HRDLRAANILVSEALCCKIADFGLA------R 383
Cdd:cd14054  80 SLCSYLRENTLDWMSSCR---MALSLTRGLAYLhtdLRRGDQykpaiaHRDLNSRNVLVKADGSCVICDFGLAmvlrgsS 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 384 IIDSEYTAQEGAKF----PIKWTAPEAIHFGV-------FTIKADVWSFGVLLMEVVTygRVP--YPGMSNPEvirnler 450
Cdd:cd14054 157 LVRGRPGAAENASIsevgTLRYMAPEVLEGAVnlrdcesALKQVDVYALGLVLWEIAM--RCSdlYPGESVPP------- 227

                ....*
gi 33469982 451 gYRMP 455
Cdd:cd14054 228 -YQMP 231
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
246-448 4.09e-17

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: 81.20  E-value: 4.09e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMKV-AIKTLKE-GTMSPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTEYMARGCLLD 322
Cdd:cd14191   9 RLGSGKFGQVFRLVEKKTKKVwAGKFFKAySAKEKENIRQEISIMNCLHHPKLVQcVDAFEEKANIVMVLEMVSGGELFE 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIA--DFGLARIIDSEYTAQEGAKFPiK 400
Cdd:cd14191  89 RI-IDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTKIKliDFGLARRLENAGSLKVLFGTP-E 166
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 33469982 401 WTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNL 448
Cdd:cd14191 167 FVAPEVINYEPIGYATDMWSIGVICYILVS-GLSPFMGDNDNETLANV 213
SH3_Lck cd12005
Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of ...
63-115 4.16e-17

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member 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. 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212938 [Multi-domain]  Cd Length: 54  Bit Score: 75.25  E-value: 4.16e-17
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 33469982  63 VVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVAR 115
Cdd:cd12005   2 VVALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAQSLTTGQEGFIPFNFVAK 54
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
242-383 4.24e-17

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: 82.03  E-value: 4.24e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMK-VAIKTL-----KEGTmsPEAFLGEANVMKALQHERLVRLYAVVTKEP-------- 307
Cdd:cd07865  15 EKLAKIGQGTFGEVFKARHRKTGQiVALKKVlmeneKEGF--PITALREIKILQLLKHENVVNLIEICRTKAtpynrykg 92
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 308 -IYIVTEYmargCLLDF--LKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR 383
Cdd:cd07865  93 sIYLVFEF----CEHDLagLLSNKNVKFTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLAR 167
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
247-438 4.40e-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: 81.12  E-value: 4.40e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLKE----GTMSPEAFLGEANVMKALQHERLVRLYAV-VTKEPIYIVTEYMARGCL 320
Cdd:cd05572   1 LGVGGFGRVELVQLKSKGRTfALKCVKKrhivQTRQQEHIFSEKEILEECNSPFIVKLYRTfKDKKYLYMLMEYCLGGEL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKtDEGsrlslprLIDMS------AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSeytaqeG 394
Cdd:cd05572  81 WTILR-DRG-------LFDEYtarfytACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGS------G 146
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982 395 AKfpiKWT--------APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd05572 147 RK---TWTfcgtpeyvAPEIILNKGYDFSVDYWSLGILLYELLT-GRPPFGG 194
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
243-451 4.55e-17

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: 81.38  E-value: 4.55e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGT-------MSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTE 313
Cdd:cd14105   9 IGEELGSGQFAVVKKCREKSTGLEyAAKFIKKRRskasrrgVSREDIEREVSILRQVLHPNIITLHDVFeNKTDVVLILE 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC----CKIADFGLARIID--S 387
Cdd:cd14105  89 LVAGGELFDFLAEKES--LSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVpiprIKLIDFGLAHKIEdgN 166
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 388 EYTAQEGAKfpiKWTAPEAIHFGVFTIKADVWSFGvllmeVVTY----GRVPYPGMSNPEVIRNLERG 451
Cdd:cd14105 167 EFKNIFGTP---EFVAPEIVNYEPLGLEADMWSIG-----VITYillsGASPFLGDTKQETLANITAV 226
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
237-464 4.69e-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: 4.69e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGYYKNN-MKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTE 313
Cdd:cd06659  19 PRQLLENYVKIGEGSTGVVCIAREKHSgRQVAVKMMDlRKQQRRELLFNEVVIMRDYQHPNVVEMYkSYLVGEELWVLME 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTdegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE 393
Cdd:cd06659  99 YLQGGALTDIVSQ---TRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQISKDVPKRK 175
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLErgyrmprpDTCPPEL 464
Cdd:cd06659 176 SLVGTPYWMAPEVISRCPYGTEVDIWSLGIMVIEMVD-GEPPYFSDSPVQAMKRLR--------DSPPPKL 237
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
245-482 5.46e-17

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: 81.37  E-value: 5.46e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNmKVAIK---TLKEGTMSPEAFLGEANVMKalqHERLVRLYAVVTK-----EPIYIVTEYMA 316
Cdd:cd14144   1 RSVGKGRYGEVWKGKWRGE-KVAVKiffTTEEASWFRETEIYQTVLMR---HENILGFIAADIKgtgswTQLYLITDYHE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKtdeGSRLSLPRLIDMSAQIAEGMAYIE--------RMNSIHRDLRAANILVSEALCCKIADFGLA------ 382
Cdd:cd14144  77 NGSLYDFLR---GNTLDTQSMLKLAYSAACGLAHLHteifgtqgKPAIAHRDIKSKNILVKKNGTCCIADLGLAvkfise 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 -RIIDSEYTAQEGAKfpiKWTAPEAI-------HFGVFtIKADVWSFGVLLMEV----VTYG-----RVPY-------PG 438
Cdd:cd14144 154 tNEVDLPPNTRVGTK---RYMAPEVLdeslnrnHFDAY-KMADMYSFGLVLWEIarrcISGGiveeyQLPYydavpsdPS 229
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 33469982 439 MSNPEVIRNLERgYRMPRP-----DTCPPELYRgVIAECWRSRPEERPT 482
Cdd:cd14144 230 YEDMRRVVCVER-RRPSIPnrwssDEVLRTMSK-LMSECWAHNPAARLT 276
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
247-438 5.55e-17

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: 81.85  E-value: 5.55e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVVTK--EPIYIVTEYMArgcl 320
Cdd:cd07856  18 VGMGAFGLVCSARDQlTGQNVAVKKIMKPFSTPvlaKRTYRELKLLKHLRHENIISLSDIFISplEDIYFVTELLG---- 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 ldflkTDEGSRLSLPRLIDMSAQ-----IAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGA 395
Cdd:cd07856  94 -----TDLHRLLTSRPLEKQFIQyflyqILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLARIQDPQMTGYVST 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 33469982 396 KFpikWTAPE-AIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd07856 169 RY---YRAPEiMLTWQKYDVEVDIWSAGCIFAEMLE-GKPLFPG 208
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
241-482 5.95e-17

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 82.18  E-value: 5.95e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  241 LRLVRKLGSGQFGEVWMGYYKNNMKV-AIKTL---KEGTMSPEaFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYM 315
Cdd:PLN00034  76 LERVNRIGSGAGGTVYKVIHRPTGRLyALKVIygnHEDTVRRQ-ICREIEILRDVNHPNVVKCHDMFDHNgEIQVLLEFM 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  316 ARGCLldflktdEGSRL-SLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEG 394
Cdd:PLN00034 155 DGGSL-------EGTHIaDEQFLADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRILAQTMDPCNS 227
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  395 AKFPIKWTAPEAIHF----GVFTIKA-DVWSFGVLLMEVVtYGRVPYP--------------GMSNPevirnlergyrmP 455
Cdd:PLN00034 228 SVGTIAYMSPERINTdlnhGAYDGYAgDIWSLGVSILEFY-LGRFPFGvgrqgdwaslmcaiCMSQP------------P 294
                        250       260
                 ....*....|....*....|....*...
gi 33469982  456 R-PDTCPPElYRGVIAECWRSRPEERPT 482
Cdd:PLN00034 295 EaPATASRE-FRHFISCCLQREPAKRWS 321
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
226-428 6.17e-17

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: 81.23  E-value: 6.17e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 226 QNPwaQDEWEIprqslrlVRKLGSGQFGEVWMGYYKNNMKVA----IKTLKEGTMspEAFLGEANVMKALQHERLVRLY- 300
Cdd:cd06643   1 LNP--EDFWEI-------VGELGDGAFGKVYKAQNKETGILAaakvIDTKSEEEL--EDYMVEIDILASCDHPNIVKLLd 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 301 AVVTKEPIYIVTEYMARGCLlDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFG 380
Cdd:cd06643  70 AFYYENNLWILIEFCAGGAV-DAVMLELERPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFG 148
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 381 LAriIDSEYTAQEGAKF---PIkWTAPEAIHFGV-----FTIKADVWSFGVLLMEV 428
Cdd:cd06643 149 VS--AKNTRTLQRRDSFigtPY-WMAPEVVMCETskdrpYDYKADVWSLGVTLIEM 201
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
246-443 6.35e-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: 80.99  E-value: 6.35e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYK-NNMKVAIKTLK----EGTmsPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGc 319
Cdd:cd07836   7 KLGEGTYATVYKGRNRtTGEIVALKEIHldaeEGT--PSTAIREISLMKELKHENIVRLHDVIhTENKLMLVFEYMDKD- 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTdEGSRLSLPRLIDMS--AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKF 397
Cdd:cd07836  84 LKKYMDT-HGVRGALDPNTVKSftYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAFGIPVNTFSNEVV 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 33469982 398 PIKWTAPEAIhFG--VFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPE 443
Cdd:cd07836 163 TLWYRAPDVL-LGsrTYSTSIDIWSVGCIMAEMIT-GRPLFPGTNNED 208
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
242-456 6.68e-17

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: 81.58  E-value: 6.68e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM----SPEAFLGEANVMKAL---QHERLVRLYAVV-TKEPIYIVT 312
Cdd:cd05589   2 RCIAVLGRGHFGKVLLAEYKPTGELfAIKALKKGDIiardEVESLMCEKRIFETVnsaRHPFLVNLFACFqTPEHVCFVM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGCLLDFLKTDEgsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiidseytaq 392
Cdd:cd05589  82 EYAAGGDLMMHIHEDV---FSEPRAVFYAACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCK--------- 149
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 393 EGAKFPIK---------WTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEV---IRNLErgYRMPR 456
Cdd:cd05589 150 EGMGFGDRtstfcgtpeFLAPEVLTDTSYTRAVDWWGLGVLIYEMLV-GESPFPGDDEEEVfdsIVNDE--VRYPR 222
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
64-114 6.73e-17

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) 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. 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 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212939 [Multi-domain]  Cd Length: 56  Bit Score: 74.70  E-value: 6.73e-17
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982  64 VALYDYTAMNDRDLQMLKGEKLQVLKGT-GDWWLARSLVTGREGYVPSNFVA 114
Cdd:cd12006   4 VALYDYEARTEDDLSFHKGEKFQILNSSeGDWWEARSLTTGETGYIPSNYVA 55
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
239-427 8.44e-17

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: 80.70  E-value: 8.44e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTM----SPEAFLGEANVMKALQHERLVRLYAvVTKEP--IYIV 311
Cdd:cd05580   1 DDFEFLKTLGTGSFGRVRLVKHKDSGKyYALKILKKAKIiklkQVEHVLNEKRILSEVRHPFIVNLLG-SFQDDrnLYMV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLktDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDseyta 391
Cdd:cd05580  80 MEYVPGGELFSLL--RRSGRFPNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAKRVK----- 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 33469982 392 qegakfPIKWT--------APEAIHFGVFTIKADVWSFGVLLME 427
Cdd:cd05580 153 ------DRTYTlcgtpeylAPEIILSKGHGKAVDWWALGILIYE 190
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
244-491 1.17e-16

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: 79.85  E-value: 1.17e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRlYAVVTKE--PIYIVTEYMAR 317
Cdd:cd08218   5 IKKIGEGSFGKALLVKSKEDGKqYVIKEINISKMSPkerEESRKEVAVLSKMKHPNIVQ-YQESFEEngNLYIVMDYCDG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSeytAQEGAKF 397
Cdd:cd08218  84 GDLYKRINAQRGVLFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNS---TVELART 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 398 PIK---WTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELyRGVIAECWR 474
Cdd:cd08218 161 CIGtpyYLSPEICENKPYNNKSDIWALGCVLYEMCTL-KHAFEAGNMKNLVLKIIRGSYPPVPSRYSYDL-RSLVSQLFK 238
                       250
                ....*....|....*..
gi 33469982 475 SRPEERPTfefLQSVLE 491
Cdd:cd08218 239 RNPRDRPS---INSILE 252
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
229-491 1.20e-16

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: 79.62  E-value: 1.20e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 229 WAQDEWEIPRqslrlvrKLGSGQFGEVWMGYYKNN-----MKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAV- 302
Cdd:cd14116   2 WALEDFEIGR-------PLGKGKFGNVYLAREKQSkfilaLKVLFKAQLEKAGVEHQLRREVEIQSHLRHPNILRLYGYf 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 303 --VTKepIYIVTEYMARGCLldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFG 380
Cdd:cd14116  75 hdATR--VYLILEYAPLGTV--YRELQKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFG 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 381 LA-RIIDSEYTAQEGAkfpIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLER-GYRMPRPD 458
Cdd:cd14116 151 WSvHAPSSRRTTLCGT---LDYLPPEMIEGRMHDEKVDLWSLGVLCYEFLV-GKPPFEANTYQETYKRISRvEFTFPDFV 226
                       250       260       270
                ....*....|....*....|....*....|...
gi 33469982 459 TcppELYRGVIAECWRSRPEERPTfefLQSVLE 491
Cdd:cd14116 227 T---EGARDLISRLLKHNPSQRPM---LREVLE 253
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
222-482 1.37e-16

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: 80.47  E-value: 1.37e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 222 RPAPQNPWAQDEW--EIPRQSLRLVRKLGSGQFGEVWMGYYK-NNMKVAIKTL----KEGTMSPEAFLGEANVMKALQHE 294
Cdd:cd06633   2 KGVLKDPEIADLFykDDPEEIFVDLHEIGHGSFGAVYFATNShTNEVVAIKKMsysgKQTNEKWQDIIKEVKFLQQLKHP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 295 RLVRLYAVVTKE-PIYIVTEYmARGCLLDFLKTDEgSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC 373
Cdd:cd06633  82 NTIEYKGCYLKDhTAWLVMEY-CLGSASDLLEVHK-KPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQ 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 374 CKIADFGLARIIdSEYTAQEGAKFpikWTAPE---AIHFGVFTIKADVWSFGVLLMEVVTYGrvpyPGMSNPEVIRNLer 450
Cdd:cd06633 160 VKLADFGSASIA-SPANSFVGTPY---WMAPEvilAMDEGQYDGKVDIWSLGITCIELAERK----PPLFNMNAMSAL-- 229
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 33469982 451 gYRMPRPDTcpPEL--------YRGVIAECWRSRPEERPT 482
Cdd:cd06633 230 -YHIAQNDS--PTLqsnewtdsFRGFVDYCLQKIPQERPS 266
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
242-488 1.47e-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: 79.68  E-value: 1.47e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKN-NMKVAIKTL---KEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMA 316
Cdd:cd14069   4 DLVQTLGEGAFGEVFLAVNRNtEEAVAVKFVdmkRAPGDCPENIKKEVCIQKMLSHKNVVRFYgHRREGEFQYLFLEYAS 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGsrlslprlidMS--------AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA---RII 385
Cdd:cd14069  84 GGELFDKIEPDVG----------MPedvaqfyfQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLAtvfRYK 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 DSE--YTAQEGAkfpIKWTAPEAIHFGVFTI-KADVWSFGVLLMEVVTyGRVPY--PGMSNPEVI--RNLERGYRMP--R 456
Cdd:cd14069 154 GKErlLNKMCGT---LPYVAPELLAKKKYRAePVDVWSCGIVLFAMLA-GELPWdqPSDSCQEYSdwKENKKTYLTPwkK 229
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 457 PDTCPPELYRGVIAEcwrsRPEERPTFEFLQS 488
Cdd:cd14069 230 IDTAALSLLRKILTE----NPNKRITIEDIKK 257
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
247-456 1.53e-16

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: 80.34  E-value: 1.53e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLK----------EGTMSPEAFLGEANvmkalQHERLVRLYAVV-TKEPIYIVTEY 314
Cdd:cd05570   3 LGKGSFGKVMLAERKKTDELyAIKVLKkeviiedddvECTMTEKRVLALAN-----RHPFLTGLHACFqTEDRLYFVMEY 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLdfLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR--IIDSEYTaq 392
Cdd:cd05570  78 VNGGDLM--FHIQRARRFTEERARFYAAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKegIWGGNTT-- 153
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 393 egAKF---PiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRN-LERGYRMPR 456
Cdd:cd05570 154 --STFcgtP-DYIAPEILREQDYGFSVDWWALGVLLYEMLA-GQSPFEGDDEDELFEAiLNDEVLYPR 217
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
243-436 1.54e-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: 79.38  E-value: 1.54e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYK-NNMKVAIKTL---KEGTMSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMAR 317
Cdd:cd14074   7 LEETLGRGHFAVVKLARHVfTGEKVAVKVIdktKLDDVSKAHLFQEVRCMKLVQHPNVVRLYEVIdTQTKLYLILELGDG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDF-LKTDEGSRLSLPRLIdmSAQIAEGMAYIERMNSIHRDLRAANILVSEAL-CCKIADFGLARiidseyTAQEGA 395
Cdd:cd14074  87 GDMYDYiMKHENGLNEDLARKY--FRQIVSAISYCHKLHVVHRDLKPENVVFFEKQgLVKLTDFGFSN------KFQPGE 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 33469982 396 KF-----PIKWTAPEaIHFGVF--TIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd14074 159 KLetscgSLAYSAPE-ILLGDEydAPAVDIWSLGVILYMLVC-GQPPF 204
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
247-492 1.59e-16

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: 80.25  E-value: 1.59e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMkVAIKTLKEG-----TMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIY-IVTEYMARGCL 320
Cdd:cd14159   1 IGEGGFGCVYQAVMRNTE-YAVKRLKEDseldwSVVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYcLIYVYLPNGSL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTDEGS-RLSLPRLIDMSAQIAEGMAYIERMNS--IHRDLRAANILVSEALCCKIADFGLARIidSEYTAQEGAKF 397
Cdd:cd14159  80 EDRLHCQVSCpCLSWSQRLHVLLGTARAIQYLHSDSPslIHGDVKSSNILLDAALNPKLGDFGLARF--SRRPKQPGMSS 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 398 PIKWTA----------PEAIHFGVFTIKADVWSFGVLLMEVVT-------------------------YGRVPYPGMSNP 442
Cdd:cd14159 158 TLARTQtvrgtlaylpEEYVKTGTLSVEIDVYSFGVVLLELLTgrramevdscsptkylkdlvkeeeeAQHTPTTMTHSA 237
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 443 E-----VIRNLERGYRMPRPDTCPPELYRGV---IAECWRSRPEERPTFEFLQSVLED 492
Cdd:cd14159 238 EaqaaqLATSICQKHLDPQAGPCPPELGIEIsqlACRCLHRRAKKRPPMTEVFQELER 295
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
62-114 1.61e-16

Src homology 3 domain of Yes Protein Tyrosine Kinase; 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 73.53  E-value: 1.61e-16
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGT-GDWWLARSLVTGREGYVPSNFVA 114
Cdd:cd12007   2 IFVALYDYEARTTEDLSFKKGERFQIINNTeGDWWEARSIATGKNGYIPSNYVA 55
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
240-441 1.77e-16

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: 79.85  E-value: 1.77e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWMGY-YKNNMKVAIK-TLKEGTMSPeaflGEANVMKALQHERLVRL-YAVVTKEP------IYI 310
Cdd:cd14137   5 SYTIEKVIGSGSFGVVYQAKlLETGEVVAIKkVLQDKRYKN----RELQIMRRLKHPNIVKLkYFFYSSGEkkdevyLNL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMArGCLLDFLKTDEGSRLSLP----RLIdmSAQIAEGMAYIERMNSIHRDLRAANILVSEALC-CKIADFGLARII 385
Cdd:cd14137  81 VMEYMP-ETLYRVIRHYSKNKQTIPiiyvKLY--SYQLFRGLAYLHSLGICHRDIKPQNLLVDPETGvLKLCDFGSAKRL 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 386 D----------SEYtaqegakfpikWTAPEAIhFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSN 441
Cdd:cd14137 158 VpgepnvsyicSRY-----------YRAPELI-FGAtdYTTAIDIWSAGCVLAELLL-GQPLFPGESS 212
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
243-436 2.34e-16

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: 78.83  E-value: 2.34e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMK-VAIK-TLKEGTMSPE--AFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYmAR 317
Cdd:cd14002   5 VLELIGEGSFGKVYKGRRKYTGQvVALKfIPKRGKSEKElrNLRQEIEILRKLNHPNIIEMLdSFETKKEFVVVTEY-AQ 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEgsrlSLP----RLIdmSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSE---YT 390
Cdd:cd14002  84 GELFQILEDDG----TLPeeevRSI--AKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAMSCNtlvLT 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 391 AqegakfpIKWT----APEAIHFGVFTIKADVWSFGVLLMEVVtYGRVPY 436
Cdd:cd14002 158 S-------IKGTplymAPELVQEQPYDHTADLWSLGCILYELF-VGQPPF 199
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
243-436 2.53e-16

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: 79.07  E-value: 2.53e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNM------KVAIKTLKEGTMSPEA----FLGEANVMKALQHERLVRLYAVV-TKEPIYIV 311
Cdd:cd14076   5 LGRTLGEGEFGKVKLGWPLPKAnhrsgvQVAIKLIRRDTQQENCqtskIMREINILKGLTHPNIVRLLDVLkTKKYIGIV 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDF------LKTDEGSRLSlprlidmsAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLArii 385
Cdd:cd14076  85 LEFVSGGELFDYilarrrLKDSVACRLF--------AQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFA--- 153
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 386 dSEYTAQEGAKFPIK-----WTAPEAIHFGVF--TIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd14076 154 -NTFDHFNGDLMSTScgspcYAAPELVVSDSMyaGRKADIWSCGVILYAMLA-GYLPF 209
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
231-443 2.71e-16

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: 78.99  E-value: 2.71e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 231 QDEWEIPRQSLRLVrkLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSP-EAFLGEANVMKALQHERLVRLYAVVTKEPI 308
Cdd:cd06624   2 EYEYEYDESGERVV--LGKGTFGVVYAARdLSTQVRIAIKEIPERDSREvQPLHEEIALHSRLSHKNIVQYLGSVSEDGF 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 Y-IVTEYMARGCLLDFLKTDEGS-RLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSE-ALCCKIADFG----L 381
Cdd:cd06624  80 FkIFMEQVPGGSLSALLRSKWGPlKDNENTIGYYTKQILEGLKYLHDNKIVHRDIKGDNVLVNTySGVVKISDFGtskrL 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33469982 382 ARIidSEYTaqEGAKFPIKWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPE 443
Cdd:cd06624 160 AGI--NPCT--ETFTGTLQYMAPEVIDKGQrgYGPPADIWSLGCTIIEMAT-GKPPFIELGEPQ 218
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
237-486 2.80e-16

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: 79.68  E-value: 2.80e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLK-EGTMSPEAF---LGEANVMKALQHERLVRLYAVVTKE-PIYI 310
Cdd:cd06634  13 PEKLFSDLREIGHGSFGAVYFARdVRNNEVVAIKKMSySGKQSNEKWqdiIKEVKFLQKLRHPNTIEYRGCYLREhTAWL 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYmARGCLLDFLKTDEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIdSEYT 390
Cdd:cd06634  93 VMEY-CLGSASDLLEVHKKP-LQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIM-APAN 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 391 AQEGAKFpikWTAPE---AIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRG 467
Cdd:cd06634 170 SFVGTPY---WMAPEvilAMDEGQYDGKVDVWSLGITCIELAER-KPPLFNMNAMSALYHIAQNESPALQSGHWSEYFRN 245
                       250
                ....*....|....*....
gi 33469982 468 VIAECWRSRPEERPTFEFL 486
Cdd:cd06634 246 FVDSCLQKIPQDRPTSDVL 264
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
244-461 2.84e-16

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: 79.65  E-value: 2.84e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYK--NNMkVAIKTLK----EGtmSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd07872  11 LEKLGEGTYATVFKGRSKltENL-VALKEIRleheEG--APCTAIREVSLLKDLKHANIVTLHDIVhTDKSLTLVFEYLD 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGclLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiIDSEYTAQEGAK 396
Cdd:cd07872  88 KD--LKQYMDDCGNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR-AKSVPTKTYSNE 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 397 FPIKWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRPDTCP 461
Cdd:cd07872 165 VVTLWYRPPDVLLGSseYSTQIDMWGVGCIFFEMAS-GRPLFPGSTVEDELHLIFRLLGTPTEETWP 230
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
237-436 3.03e-16

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: 78.82  E-value: 3.03e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTE 313
Cdd:cd06647   5 PKKKYTRFEKIGQGASGTVYTAIdVATGQEVAIKQMNlQQQPKKELIINEILVMRENKNPNIVNyLDSYLVGDELWVVME 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLK---TDEGSRLSLPRlidmsaQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYT 390
Cdd:cd06647  85 YLAGGSLTDVVTetcMDEGQIAAVCR------ECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQS 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 33469982 391 AQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd06647 159 KRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY 203
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
243-482 3.19e-16

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: 78.48  E-value: 3.19e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKN-NMKVAIKTLK--EGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARG 318
Cdd:cd08219   4 VLRVVGEGSFGRALLVQHVNsDQKYAMKEIRlpKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGhLYIVMEYCDGG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYT---AQEGA 395
Cdd:cd08219  84 DLMQKIKLQRGKLFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTSPGAyacTYVGT 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELyRGVIAECWRS 475
Cdd:cd08219 164 PY---YVPPEIWENMPYNNKSDIWSLGCILYELCTL-KHPFQANSWKNLILKVCQGSYKPLPSHYSYEL-RSLIKQMFKR 238

                ....*..
gi 33469982 476 RPEERPT 482
Cdd:cd08219 239 NPRSRPS 245
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
244-484 3.32e-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: 78.24  E-value: 3.32e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMgYYK--NNMKVAIKTLKEGTMSPEA---FLGEANVMKALQHERLVRLYA-VVTKEPIYIVTEYMAR 317
Cdd:cd08221   5 VRVLGRGAFGEAVL-YRKteDNSLVVWKEVNLSRLSEKErrdALNEIDILSLLNHDNIITYYNhFLDGESLFIEMEYCNG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKF 397
Cdd:cd08221  84 GNLHDKIAQQKNQLFPEEVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISKVLDSESSMAESIVG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 398 PIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVpyPGMSNP-EVIRNLERGYRMPRPDTCPPELyRGVIAECWRSR 476
Cdd:cd08221 164 TPYYMSPELVQGVKYNFKSDIWAVGCVLYELLTLKRT--FDATNPlRLAVKIVQGEYEDIDEQYSEEI-IQLVHDCLHQD 240

                ....*...
gi 33469982 477 PEERPTFE 484
Cdd:cd08221 241 PEDRPTAE 248
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
237-482 3.45e-16

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: 78.92  E-value: 3.45e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGYYKNNMKVA----IKTLKEGTMspEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIV 311
Cdd:cd06644  10 PNEVWEIIGELGDGAFGKVYKAKNKETGALAaakvIETKSEEEL--EDYMVEIEILATCNHPYIVKLLgAFYWDGKLWIM 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCL-LDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAriIDSEYT 390
Cdd:cd06644  88 IEFCPGGAVdAIMLELDRG--LTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVS--AKNVKT 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 391 AQEGAKF---PIkWTAPEAIHFGV-----FTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERGY--RMPRPDTC 460
Cdd:cd06644 164 LQRRDSFigtPY-WMAPEVVMCETmkdtpYDYKADIWSLGITLIEMAQI-EPPHHELNPMRVLLKIAKSEppTLSQPSKW 241
                       250       260
                ....*....|....*....|..
gi 33469982 461 PPElYRGVIAECWRSRPEERPT 482
Cdd:cd06644 242 SME-FRDFLKTALDKHPETRPS 262
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
247-440 4.21e-16

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: 78.47  E-value: 4.21e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-VAIKTLK----EGTMsPEAFLGEANVMKALQ---HERLVRLYAV-----VTKE-PIYIVT 312
Cdd:cd07838   7 IGEGAYGTVYKARDLQDGRfVALKKVRvplsEEGI-PLSTIREIALLKQLEsfeHPNVVRLLDVchgprTDRElKLTLVF 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 EYMARGcLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYtaq 392
Cdd:cd07838  86 EHVDQD-LATYLDKCPKPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLARIYSFEM--- 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 33469982 393 egAKFPIKWT----APEAIHFGVFTIKADVWSFGVLLMEVvtYGRVP-YPGMS 440
Cdd:cd07838 162 --ALTSVVVTlwyrAPEVLLQSSYATPVDMWSVGCIFAEL--FNRRPlFRGSS 210
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
235-499 4.46e-16

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: 78.94  E-value: 4.46e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTL----KEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKE-PI 308
Cdd:cd06635  21 EDPEKLFSDLREIGHGSFGAVYFARdVRTSEVVAIKKMsysgKQSNEKWQDIIKEVKFLQRIKHPNSIEYKGCYLREhTA 100
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 YIVTEYmARGCLLDFLKTDEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIdSE 388
Cdd:cd06635 101 WLVMEY-CLGSASDLLEVHKKP-LQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIA-SP 177
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGAKFpikWTAPE---AIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELY 465
Cdd:cd06635 178 ANSFVGTPY---WMAPEvilAMDEGQYDGKVDVWSLGITCIELAER-KPPLFNMNAMSALYHIAQNESPTLQSNEWSDYF 253
                       250       260       270
                ....*....|....*....|....*....|....
gi 33469982 466 RGVIAECWRSRPEERPTFEFLqsvLEDFYTATER 499
Cdd:cd06635 254 RNFVDSCLQKIPQDRPTSEEL---LKHMFVLRER 284
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
246-447 4.59e-16

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: 78.10  E-value: 4.59e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSpeAFLGEANVMKALQHERLVRLYA-VVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd14010   7 EIGRGKHSVVYKGRRKGTIEfVAIKCVDKSKRP--EVLNEVRLTHELKHPNVLKFYEwYETSNHLWLVVEYCTGGDLETL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII------------DSEYTA 391
Cdd:cd14010  85 LRQDG--NLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREgeilkelfgqfsDEGNVN 162
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIK----WTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRN 447
Cdd:cd14010 163 KVSKKQAKRgtpyYMAPELFQGGVHSFASDLWALGCVLYEMFT-GKPPFVAESFTELVEK 221
SH3_Src cd12008
Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or ...
64-114 5.69e-16

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and 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. 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212941 [Multi-domain]  Cd Length: 56  Bit Score: 72.07  E-value: 5.69e-16
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982  64 VALYDYTAMNDRDLQMLKGEKLQVLKGT-GDWWLARSLVTGREGYVPSNFVA 114
Cdd:cd12008   3 VALYDYESRTETDLSFKKGERLQIVNNTeGDWWLAHSLTTGQTGYIPSNYVA 54
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
240-438 6.65e-16

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: 78.18  E-value: 6.65e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVW-MGYYKNNMKVAIKTLKEGTMSPEA--FLGEANV-MKALQHERLVRLY-AVVTKEPIYIVTEY 314
Cdd:cd06618  16 DLENLGEIGSGTCGQVYkMRHKKTGHVMAVKQMRRSGNKEENkrILMDLDVvLKSHDCPYIVKCYgYFITDSDVFICMEL 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARgCLLDFLKTDEGSrlsLPRLI--DMSAQIAEGMAYI-ERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSE-Y 389
Cdd:cd06618  96 MST-CLDKLLKRIQGP---IPEDIlgKMTVSIVKALHYLkEKHGVIHRDVKPSNILLDESGNVKLCDFGISgRLVDSKaK 171
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982 390 TAQEGAKfpiKWTAPEAI---HFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd06618 172 TRSAGCA---AYMAPERIdppDNPKYDIRADVWSLGISLVELAT-GQFPYRN 219
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
247-463 8.10e-16

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: 77.87  E-value: 8.10e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNmKVAIKTLKegTMSPEAFLGEANVMKA--LQHERLVRLYAVVTKE-----PIYIVTEYMARGC 319
Cdd:cd14143   3 IGKGRFGEVWRGRWRGE-DVAVKIFS--SREERSWFREAEIYQTvmLRHENILGFIAADNKDngtwtQLWLVSDYHEHGS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTdegSRLSLPRLIDMSAQIAEGMAYIErMNSI---------HRDLRAANILVSEALCCKIADFGLARIIDSE-- 388
Cdd:cd14143  80 LFDYLNR---YTVTVEGMIKLALSIASGLAHLH-MEIVgtqgkpaiaHRDLKSKNILVKKNGTCCIADLGLAVRHDSAtd 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 -----YTAQEGAKfpiKWTAPEAI-------HFGVFTiKADVWSFGVLLMEVvtyGRVPYPGMSNPEvirnlergYRMPR 456
Cdd:cd14143 156 tidiaPNHRVGTK---RYMAPEVLddtinmkHFESFK-RADIYALGLVFWEI---ARRCSIGGIHED--------YQLPY 220

                ....*..
gi 33469982 457 PDTCPPE 463
Cdd:cd14143 221 YDLVPSD 227
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
243-430 8.27e-16

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: 77.92  E-value: 8.27e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKN-NMKVAIKTL-----KEGTmsPEAFLGEANVMKALQHERLVRLYAVVT-----------K 305
Cdd:cd07864  11 IIGIIGEGTYGQVYKAKDKDtGELVALKKVrldneKEGF--PITAIREIKILRQLNHRSVVNLKEIVTdkqdaldfkkdK 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 EPIYIVTEYMARGcLLDFLKTdegsrlslpRLIDMS--------AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIA 377
Cdd:cd07864  89 GAFYLVFEYMDHD-LMGLLES---------GLVHFSedhiksfmKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLA 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 378 DFGLARIIDSEYTAQEGAKFPIKWTAPEAIHFG--VFTIKADVWSFGVLLMEVVT 430
Cdd:cd07864 159 DFGLARLYNSEESRPYTNKVITLWYRPPELLLGeeRYGPAIDVWSCGCILGELFT 213
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
242-440 1.11e-15

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270841 [Multi-domain]  Cd Length: 337  Bit Score: 77.98  E-value: 1.11e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGY-YKNNMKVAIK--------------TLKEGTmspeaFLGEANvmkalQHERLVRLYAVVTKE 306
Cdd:cd07852  10 EILKKLGKGAYGIVWKAIdKKTGEVVALKkifdafrnatdaqrTFREIM-----FLQELN-----DHPNIIKLLNVIRAE 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 ---PIYIVTEYMA--------RGCLLDFLKtdegsrlslpRLIdmSAQIAEGMAYIERMNSIHRDLRAANILV-SEALCc 374
Cdd:cd07852  80 ndkDIYLVFEYMEtdlhavirANILEDIHK----------QYI--MYQLLKALKYLHSGGVIHRDLKPSNILLnSDCRV- 146
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 375 KIADFGLARIIDSEytaQEGAKFPI-------KW-TAPEaIHFGV--FTIKADVWSFGVLLMEVVTyGRVPYPGMS 440
Cdd:cd07852 147 KLADFGLARSLSQL---EEDDENPVltdyvatRWyRAPE-ILLGStrYTKGVDMWSVGCILGEMLL-GKPLFPGTS 217
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
124-205 1.15e-15

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 71.91  E-value: 1.15e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 124 WFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTqgelIKHYKIRCLDEGGYYISPRITFPSLQALVQ 203
Cdd:cd10360   2 WYFSGISRTQAQQLLLSPPNEPGAFLIRPSESSLGGYSLSVRAQAK----VCHYRICMAPSGSLYLQKGRLFPGLEELLA 77

                ..
gi 33469982 204 HY 205
Cdd:cd10360  78 YY 79
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
239-486 1.30e-15

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: 77.23  E-value: 1.30e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEgTMSPE---AFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTE 313
Cdd:cd06619   1 QDIQYQEILGHGNGGTVYKAYHLLTRRIlAVKVIPL-DITVElqkQIMSELEILYKCDSPYIIGFYgAFFVENRISICTE 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTDEgsrlslPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR-IIDSEYTAQ 392
Cdd:cd06619  80 FMDGGSLDVYRKIPE------HVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTqLVNSIAKTY 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYpgmsnPEVIRNleRGYRMPRP------DTCPPELYR 466
Cdd:cd06619 154 VGTN---AYMAPERISGEQYGIHSDVWSLGISFMELAL-GRFPY-----PQIQKN--QGSLMPLQllqcivDEDPPVLPV 222
                       250       260
                ....*....|....*....|....*...
gi 33469982 467 G--------VIAECWRSRPEERPTFEFL 486
Cdd:cd06619 223 GqfsekfvhFITQCMRKQPKERPAPENL 250
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
237-464 1.31e-15

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: 77.39  E-value: 1.31e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGYYKNNMK-VAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTE 313
Cdd:cd06658  20 PREYLDSFIKIGEGSTGIVCIATEKHTGKqVAVKKMDlRKQQRRELLFNEVVIMRDYHHENVVDMYnSYLVGDELWVVME 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTdegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE 393
Cdd:cd06658 100 FLEGGALTDIVTH---TRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRK 176
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLErgyrmprpDTCPPEL 464
Cdd:cd06658 177 SLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMID-GEPPYFNEPPLQAMRRIR--------DNLPPRV 238
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
246-445 1.31e-15

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: 77.41  E-value: 1.31e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGY-YKNNMKVAIKTL-----KEGTmsPEAFLGEANVMKALQHERLVRLYAVVTK---EPIYIVTEY-- 314
Cdd:cd07845  14 RIGEGTYGIVYRARdTTSGEIVALKKVrmdneRDGI--PISSLREITLLLNLRHPNIVELKEVVVGkhlDSIFLVMEYce 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 --MARgcLLDFLKTDegsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ 392
Cdd:cd07845  92 qdLAS--LLDNMPTP----FSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYGLPAKPM 165
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 393 EGAKFPIKWTAPEAIhFG--VFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVI 445
Cdd:cd07845 166 TPKVVTLWYRAPELL-LGctTYTTAIDMWAVGCILAELLA-HKPLLPGKSEIEQL 218
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
245-451 1.32e-15

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


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 76.82  E-value: 1.32e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTL---KEGTMSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGC 319
Cdd:cd14097   7 RKLGQGSFGVVIEATHKeTQTKWAIKKInreKAGSSAVKLLEREVDILKHVNHAHIIHLEEVFeTPKRMYLVMELCEDGE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEGSRLSLPRLIDMSaqIAEGMAYIERMNSIHRDLRAANILVSEA-------LCCKIADFGLA--RIIDSEYT 390
Cdd:cd14097  87 LKELLLRKGFFSENETRHIIQS--LASAVAYLHKNDIVHRDLKLENILVKSSiidnndkLNIKVTDFGLSvqKYGLGEDM 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 391 AQEGAKFPIkWTAPEAIHFGVFTIKADVWSFGVlLMEVVTYGRVPYPGMSNPEVIRNLERG 451
Cdd:cd14097 165 LQETCGTPI-YMAPEVISAHGYSQQCDIWSIGV-IMYMLLCGEPPFVAKSEEKLFEEIRKG 223
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
246-448 1.35e-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: 76.98  E-value: 1.35e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKN-NMKVAIKTLKEGT-------MSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd14194  12 ELGSGQFAVVKKCREKStGLQYAAKFIKKRRtkssrrgVSREDIEREVSILKEIQHPNVITLHEVYeNKTDVILILELVA 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC----CKIADFGLARIIDSEYTAQ 392
Cdd:cd14194  92 GGELFDFLAEKES--LTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVpkprIKIIDFGLAHKIDFGNEFK 169
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 393 EGAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNL 448
Cdd:cd14194 170 NIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITY-ILLSGASPFLGDTKQETLANV 223
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
246-441 1.64e-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: 77.08  E-value: 1.64e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKN-NMKVAIKTLKEG---TMSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCL 320
Cdd:cd07846   8 LVGEGSYGMVMKCRHKEtGQIVAIKKFLESeddKMVKKIAMREIKMLKQLRHENLVNLIEVFrRKKRWYLVFEFVDHTVL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS---EYTAQEGAKF 397
Cdd:cd07846  88 DDLEKYPNG--LDESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLAApgeVYTDYVATRW 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 33469982 398 pikWTAPEAIHFGVFTIKA-DVWSFGVLLMEVVTyGRVPYPGMSN 441
Cdd:cd07846 166 ---YRAPELLVGDTKYGKAvDVWAVGCLVTEMLT-GEPLFPGDSD 206
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
59-114 1.80e-15

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: 70.64  E-value: 1.80e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982     59 DKHFVVALYDYTAMNDRDLQMLKGEKLQVL-KGTGDWWLARsLVTGREGYVPSNFVA 114
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLeKSDDGWWKGR-LGRGKEGLFPSNYVE 56
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
247-488 1.86e-15

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: 76.32  E-value: 1.86e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEA-------FLGEANVMKALQHERLVRLYAVVTKEPIY-IVTEYMARG 318
Cdd:cd06631   9 LGKGAYGTVYCGLTSTGQLIAVKQVELDTSDKEKaekeyekLQEEVDLLKTLKHVNIVGYLGTCLEDNVVsIFMEFVPGG 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR---IIDSEYTAQE-- 393
Cdd:cd06631  89 SIASILA--RFGALEEPVFCRYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKrlcINLSSGSQSQll 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 ----GAKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYR-MPR-PDTCPPELyRG 467
Cdd:cd06631 167 ksmrGTPY---WMAPEVINETGHGRKSDIWSIGCTVFEMAT-GKPPWADMNPMAAIFAIGSGRKpVPRlPDKFSPEA-RD 241
                       250       260
                ....*....|....*....|.
gi 33469982 468 VIAECWRSRPEERPTFEFLQS 488
Cdd:cd06631 242 FVHACLTRDQDERPSAEQLLK 262
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
239-482 2.14e-15

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: 77.01  E-value: 2.14e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYYKNNmKVAIK---TLKEGTMSPEAFLGEANVMKalqHERLVRLYAVVTK-----EPIYI 310
Cdd:cd14219   5 KQIQMVKQIGKGRYGEVWMGKWRGE-KVAVKvffTTEEASWFRETEIYQTVLMR---HENILGFIAADIKgtgswTQLYL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKTdegSRLSLPRLIDMSAQIAEGMAYIE--------RMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd14219  81 ITDYHENGSLYDYLKS---TTLDTKAMLKLAYSSVSGLCHLHteifstqgKPAIAHRDLKSKNILVKKNGTCCIADLGLA 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 -------RIIDSEYTAQEGAKfpiKWTAPEAI-------HFGVFtIKADVWSFGVLLMEV----VTYG-----RVPY--- 436
Cdd:cd14219 158 vkfisdtNEVDIPPNTRVGTK---RYMPPEVLdeslnrnHFQSY-IMADMYSFGLILWEVarrcVSGGiveeyQLPYhdl 233
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 437 -PGMSNPEVIRNLERGYRMpRP--------DTCPPELYRgVIAECWRSRPEERPT 482
Cdd:cd14219 234 vPSDPSYEDMREIVCIKRL-RPsfpnrwssDECLRQMGK-LMTECWAHNPASRLT 286
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
247-457 2.23e-15

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: 76.91  E-value: 2.23e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTLKEGTM----SPEAFLGEANVMK-ALQHERLVRLYAVV-TKEPIYIVTEYMARGC 319
Cdd:cd05620   3 LGKGSFGKVLLAELKgKGEYFAVKALKKDVVliddDVECTMVEKRVLAlAWENPFLTHLYCTFqTKEHLFFVMEFLNGGD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLdFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiiDSEYTAQEGAKF-- 397
Cdd:cd05620  83 LM-FHIQDKG-RFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCK--ENVFGDNRASTFcg 158
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 398 PIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLergyRMPRP 457
Cdd:cd05620 159 TPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLI-GQSPFHGDDEDELFESI----RVDTP 213
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
244-450 2.66e-15

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: 75.78  E-value: 2.66e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMA-RGCLL 321
Cdd:cd14113  12 VAELGRGRFSVVKKCDQRGTKRaVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMAdQGRLL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLK-----TDEGSRLSLprlidmsAQIAEGMAYIERMNSIHRDLRAANILVSEALC---CKIADFGLARIIDSEYTAQE 393
Cdd:cd14113  92 DYVVrwgnlTEEKIRFYL-------REILEALQYLHNCRIAHLDLKPENILVDQSLSkptIKLADFGDAVQLNTTYYIHQ 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 394 GAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNLER 450
Cdd:cd14113 165 LLGSP-EFAAPEIILGNPVSLTSDLWSIGVLTY-VLLSGVSPFLDESVEETCLNICR 219
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
245-456 2.72e-15

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: 75.97  E-value: 2.72e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGY-YKNNMKVAIKTLKEgTMSPEAFLG-----EANVMKALQHERLVRLYAV--VTKEPIYIVTEYMA 316
Cdd:cd14165   7 INLGEGSYAKVKSAYsERLKCNVAIKIIDK-KKAPDDFVEkflprELEILARLNHKSIIKTYEIfeTSDGKVYIVMELGV 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKtdegSRLSLPRLI--DMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII--DSEYTAQ 392
Cdd:cd14165  86 QGDLLEFIK----LRGALPEDVarKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRClrDENGRIV 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 393 EGAKF--PIKWTAPEAIHFGVFTIKA-DVWSFGVLLMeVVTYGRVPYPGMSNPEVIR-NLERGYRMPR 456
Cdd:cd14165 162 LSKTFcgSAAYAAPEVLQGIPYDPRIyDIWSLGVILY-IMVCGSMPYDDSNVKKMLKiQKEHRVRFPR 228
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
243-480 3.56e-15

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: 76.94  E-value: 3.56e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM--SPE--AFLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMA 316
Cdd:cd05573   5 VIKVIGRGAFGEVWLVRDKDTGQVyAMKILRKSDMlkREQiaHVRAERDILADADSPWIVRLhYAFQDEDHLYLVMEYMP 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLktdegsrLSLPRLIDMSAQ--IAEGMAYIE---RMNSIHRDLRAANILVSEALCCKIADFGLA--------- 382
Cdd:cd05573  85 GGDLMNLL-------IKYDVFPEETARfyIAELVLALDslhKLGFIHRDIKPDNILLDADGHIKLADFGLCtkmnksgdr 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 -----RIIDSEYTAQEGAKFPIK---------------WTAPEaIHFGV-FTIKADVWSFGVLLMEVVtYGRVPYPGMSN 441
Cdd:cd05573 158 esylnDSVNTLFQDNVLARRRPHkqrrvraysavgtpdYIAPE-VLRGTgYGPECDWWSLGVILYEML-YGFPPFYSDSL 235
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 33469982 442 PEV---IRNLERGYRMPRPDTCPPE---LYRGVIAEcwrsrPEER 480
Cdd:cd05573 236 VETyskIMNWKESLVFPDDPDVSPEaidLIRRLLCD-----PEDR 275
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
245-494 5.02e-15

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: 74.96  E-value: 5.02e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVW-MGYYKNNMKVAIKTLKEGTMSP----EAFLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMARG 318
Cdd:cd14189   7 RLLGKGGFARCYeMTDLATNKTYAVKVIPHSRVAKphqrEKIVNEIELHRDLHHKHVVKFsHHFEDAENIYIFLELCSRK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFP 398
Cdd:cd14189  87 SLAHIWKARH--TLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPEQRKKTICGT 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 399 IKWTAPEAIHFGVFTIKADVWSFGVlLMEVVTYGRVPYPGMSNPEVIRNLER-GYRMPRPDTCPPelyRGVIAECWRSRP 477
Cdd:cd14189 165 PNYLAPEVLLRQGHGPESDVWSLGC-VMYTLLCGNPPFETLDLKETYRCIKQvKYTLPASLSLPA---RHLLAGILKRNP 240
                       250
                ....*....|....*..
gi 33469982 478 EERPTFEflQSVLEDFY 494
Cdd:cd14189 241 GDRLTLD--QILEHEFF 255
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
242-425 5.27e-15

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: 75.55  E-value: 5.27e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNM--KVAIKTLKEGTMSPEAF--------LGEANVMKALQHERLVRLYA-VVTKEPIYI 310
Cdd:cd14096   4 RLINKIGEGAFSNVYKAVPLRNTgkPVAIKVVRKADLSSDNLkgssraniLKEVQIMKRLSHPNIVKLLDfQESDEYYYI 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLldFLKTDEGSRLS--LPRLIdmSAQIAEGMAYIERMNSIHRDLRAANIL--------------------- 367
Cdd:cd14096  84 VLELADGGEI--FHQIVRLTYFSedLSRHV--ITQVASAVKYLHEIGVVHRDIKPENLLfepipfipsivklrkadddet 159
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 33469982 368 -VSEAL-----------CCKIADFGLARIIDSEYTaqegaKFP---IKWTAPEAIHFGVFTIKADVWSFGVLL 425
Cdd:cd14096 160 kVDEGEfipgvggggigIVKLADFGLSKQVWDSNT-----KTPcgtVGYTAPEVVKDERYSKKVDMWALGCVL 227
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
246-486 5.48e-15

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: 75.27  E-value: 5.48e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYK-NNMKVAIK----TLKEGTMSpeAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYMARGC 319
Cdd:cd06622   8 ELGKGNYGSVYKVLHRpTGVTMAMKeirlELDESKFN--QIIMELDILHKAVSPYIVDFYGAFFIEgAVYMCMEYMDAGS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LlDFLkTDEGS---RLSLPRLIDMSAQIAEGMAYI-ERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYTAQEG 394
Cdd:cd06622  86 L-DKL-YAGGVateGIPEDVLRRITYAVVKGLKFLkEEHNIIHRDVKPTNVLVNGNGQVKLCDFGVSgNLVASLAKTNIG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKfpiKWTAPEAIHFG------VFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPrPDTCPPELY--- 465
Cdd:cd06622 164 CQ---SYMAPERIKSGgpnqnpTYTVQSDVWSLGLSILEMAL-GRYPYPPETYANIFAQLSAIVDGD-PPTLPSGYSdda 238
                       250       260
                ....*....|....*....|.
gi 33469982 466 RGVIAECWRSRPEERPTFEFL 486
Cdd:cd06622 239 QDFVAKCLNKIPNRRPTYAQL 259
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
240-487 5.51e-15

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: 75.08  E-value: 5.51e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPEA--------FLGEANV-MKALQHERLVRLYAVV-TKEPI 308
Cdd:cd13993   1 RYQLISPIGEGAYGVVYLAVdLRTGRKYAIKCLYKSGPNSKDgndfqklpQLREIDLhRRVSRHPNIITLHDVFeTEVAI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 309 YIVTEYMARGCLLDFLKTDEGSRLSlPRLI-DMSAQIAEGMAYIERMNSIHRDLRAANILVS-EALCCKIADFGLARIID 386
Cdd:cd13993  81 YIVLEYCPNGDLFEAITENRIYVGK-TELIkNVFLQLIDAVKHCHSLGIYHRDIKPENILLSqDEGTVKLCDFGLATTEK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SEYTAQEGAKFpikWTAPEAIHF------GVFTIKADVWSFGVLLMEvVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTC 460
Cdd:cd13993 160 ISMDFGVGSEF---YMAPECFDEvgrslkGYPCAAGDIWSLGIILLN-LTFGRNPWKIASESDPIFYDYYLNSPNLFDVI 235
                       250       260       270
                ....*....|....*....|....*....|
gi 33469982 461 PP---ELYRgVIAECWRSRPEERPTFEFLQ 487
Cdd:cd13993 236 LPmsdDFYN-LLRQIFTVNPNNRILLPELQ 264
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
246-438 6.68e-15

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: 75.16  E-value: 6.68e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMK-VAIKTLK-----EGTmsPEAFLGEANVMKALQHERLVRLYAVVTKE-PIYIVTEYmarg 318
Cdd:cd07839   7 KIGEGTYGTVFKAKNRETHEiVALKRVRlddddEGV--PSSALREICLLKELKHKNIVRLYDVLHSDkKLTLVFEY---- 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKTDEgsrlSLPRLIDMSA------QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR---IIDSEY 389
Cdd:cd07839  81 CDQDLKKYFD----SCNGDIDPEIvksfmfQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARafgIPVRCY 156
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 33469982 390 TAQegakFPIKWTAPEAIHFG--VFTIKADVWSFGVLLMEVVTYGRVPYPG 438
Cdd:cd07839 157 SAE----VVTLWYRPPDVLFGakLYSTSIDMWSAGCIFAELANAGRPLFPG 203
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
244-430 7.43e-15

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: 74.76  E-value: 7.43e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKN-NMKVAIKTLK-----EGTmsPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEY-- 314
Cdd:cd07861   5 IEKIGEGTYGVVYKGRNKKtGQIVAMKKIRleseeEGV--PSTAIREISLLKELQHPNIVCLEDVLMQENrLYLVFEFls 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEG 394
Cdd:cd07861  83 MDLKKYLDSLPKGK--YMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAFGIPVRVYTH 160
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 33469982 395 AKFPIKWTAPEAIHFGV-FTIKADVWSFGVLLMEVVT 430
Cdd:cd07861 161 EVVTLWYRAPEVLLGSPrYSTPVDIWSIGTIFAEMAT 197
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
247-438 8.24e-15

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: 75.50  E-value: 8.24e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLK----------EGTMSPEAFLGEANvmkalQHERLVRLYAVV-TKEPIYIVTEY 314
Cdd:cd05592   3 LGKGSFGKVMLAELKGTNQYfAIKALKkdvvledddvECTMIERRVLALAS-----QHPFLTHLFCTFqTESHLFFVMEY 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLdFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI-IDSEYTAQE 393
Cdd:cd05592  78 LNGGDLM-FHIQQSG-RFDEDRARFYGAEIICGLQFLHSRGIIYRDLKLDNVLLDREGHIKIADFGMCKEnIYGENKAST 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 33469982 394 GAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd05592 156 FCGTP-DYIAPEILKGQKYNQSVDWWSFGVLLYEMLI-GQSPFHG 198
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
122-207 8.60e-15

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: 70.07  E-value: 8.60e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 122 ERWFFR--SQGRKEAERQLLA-PINKAGSFLIRESETNKGAFSLSVkdvtTQGELIKHYKIRCLDEGG---YYISPRITF 195
Cdd:cd10341   4 EPWFHGklGDGRDEAEKLLLEyCEGGDGTFLVRESETFVGDYTLSF----WRNGKVQHCRIRSRQENGekkYYLTDNLVF 79
                        90
                ....*....|..
gi 33469982 196 PSLQALVQHYSK 207
Cdd:cd10341  80 DSLYELIDYYRQ 91
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
237-488 1.09e-14

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: 74.29  E-value: 1.09e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVwmgYYKNNMK------VAIKTLKEG----TMSPEAFLgeanvMKALQHERLVRLY-AVVTK 305
Cdd:cd06646   7 PQHDYELIQRVGSGTYGDV---YKARNLHtgelaaVKIIKLEPGddfsLIQQEIFM-----VKECKHCNIVAYFgSYLSR 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 306 EPIYIVTEYMARGCLLDFLKTDegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII 385
Cdd:cd06646  79 EKLWICMEYCGGGSLQDIYHVT--GPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKI 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 DSEYTAQEGAKFPIKWTAPEAIHF---GVFTIKADVWSFGVLLMEVVTYgrvpYPGMSNPEVIRNLergYRMPRPDTCPP 462
Cdd:cd06646 157 TATIAKRKSFIGTPYWMAPEVAAVeknGGYNQLCDIWAVGITAIELAEL----QPPMFDLHPMRAL---FLMSKSNFQPP 229
                       250       260       270
                ....*....|....*....|....*....|....*
gi 33469982 463 EL---------YRGVIAECWRSRPEERPTFEFLQS 488
Cdd:cd06646 230 KLkdktkwsstFHNFVKISLTKNPKKRPTAERLLT 264
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
247-436 1.27e-14

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: 74.62  E-value: 1.27e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM----SPEAFLGEANVM-KALQHERLVRL-YAVVTKEPIYIVTEYMARGC 319
Cdd:cd05603   3 IGKGSFGKVLLAKRKCDGKFyAVKVLQKKTIlkkkEQNHIMAERNVLlKNLKHPFLVGLhYSFQTSEKLYFVLDYVNGGE 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI-IDSEYTAQEGAKFP 398
Cdd:cd05603  83 L--FFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCKEgMEPEETTSTFCGTP 160
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 33469982 399 iKWTAPEAIHFGVFTIKADVWSFGVLLMEVVtYGRVPY 436
Cdd:cd05603 161 -EYLAPEVLRKEPYDRTVDWWCLGAVLYEML-YGLPPF 196
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
247-493 1.32e-14

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: 74.34  E-value: 1.32e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-----VAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYA-----VVTKEPIYIVTEYMA 316
Cdd:cd14055   3 VGKGRFAEVWKAKLKQNASgqyetVAVKIFPYEEYASWKNEKDIFTDASLKHENILQFLTaeergVGLDRQYWLITAYHE 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTdegSRLSLPRLIDMSAQIAEGMAY---------IERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS 387
Cdd:cd14055  83 NGSLQDYLTR---HILSWEDLCKMAGSLARGLAHlhsdrtpcgRPKIPIAHRDLKSSNILVKNDGTCVLADFGLALRLDP 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYTAQE----GAKFPIKWTAPEAIHFGV-------FTiKADVWSFGVLLMEVVTygRVPYPGMSNP-------------- 442
Cdd:cd14055 160 SLSVDElansGQVGTARYMAPEALESRVnledlesFK-QIDVYSMALVLWEMAS--RCEASGEVKPyelpfgskvrerpc 236
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 33469982 443 -EVIRNL---ERGyrmpRPDTcPPELYR--------GVIAECWRSRPEERPTfefLQSVLEDF 493
Cdd:cd14055 237 vESMKDLvlrDRG----RPEI-PDSWLThqgmcvlcDTITECWDHDPEARLT---ASCVAERF 291
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
123-209 1.40e-14

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: 69.23  E-value: 1.40e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 123 RWFFRSQGRKEAERQLLAPiNKAGSFLIRESETNKGAFSLSVKdvtTQGELIKHYKIRClDEGGYYISPRITFPSLQALV 202
Cdd:cd09931   1 RWFHGHLSGKEAEKLLLEK-GKPGSFLVRESQSKPGDFVLSVR---TDDDKVTHIMIRC-QGGKYDVGGGEEFDSLTDLV 75

                ....*..
gi 33469982 203 QHYSKKG 209
Cdd:cd09931  76 EHYKKNP 82
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
243-455 1.46e-14

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: 73.98  E-value: 1.46e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMK-VAIKTL-KEG---TMSPEAFLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMA 316
Cdd:cd14209   5 RIKTLGTGSFGRVMLVRHKETGNyYAMKILdKQKvvkLKQVEHTLNEKRILQAINFPFLVKLeYSFKDNSNLYMVMEYVP 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEytaqegak 396
Cdd:cd14209  85 GGEMFSHLR--RIGRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAKRVKGR-------- 154
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 397 fpiKWT--------APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYpGMSNPEVIRNL--ERGYRMP 455
Cdd:cd14209 155 ---TWTlcgtpeylAPEIILSKGYNKAVDWWALGVLIYEMAA-GYPPF-FADQPIQIYEKivSGKVRFP 218
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
249-445 1.49e-14

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: 73.79  E-value: 1.49e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 249 SGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPEA----FLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMARG---C 319
Cdd:cd05579   3 RGAYGRVYLAKKKSTGDLyAIKVIKKRDMIRKNqvdsVLAERNILSQAQNPFVVKLyYSFQGKKNLYLVMEYLPGGdlyS 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKT-DEgsrlSLPRLIdmSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI--IDSEYTAQEGAK 396
Cdd:cd05579  83 LLENVGAlDE----DVARIY--IAEIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKVglVRRQIKLSIQKK 156
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33469982 397 FPIKWT-------------APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYpGMSNPEVI 445
Cdd:cd05579 157 SNGAPEkedrrivgtpdylAPEILLGQGHGKTVDWWSLGVILYEFLV-GIPPF-HAETPEEI 216
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
247-443 1.67e-14

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: 74.36  E-value: 1.67e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWM-----GYYKNNMkVAIKTLKEGTMSPEAFLG---EANVMKALQHERLVRL-YAVVTKEPIYIVTEYMAR 317
Cdd:cd05582   3 LGQGSFGKVFLvrkitGPDAGTL-YAMKVLKKATLKVRDRVRtkmERDILADVNHPFIVKLhYAFQTEGKLYLILDFLRG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLL-----DFLKTDEGSRLSLprlidmsAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiidsEYTAQ 392
Cdd:cd05582  82 GDLFtrlskEVMFTEEDVKFYL-------AELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSK----ESIDH 150
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 393 EGAKFP----IKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPE 443
Cdd:cd05582 151 EKKAYSfcgtVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPFQGKDRKE 204
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
250-430 1.78e-14

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: 73.80  E-value: 1.78e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 250 GQFGEVWMGYYKNNMK-VAIKTLKegtMSPEA--F----LGEANVMKALQHERLVRLYAVV---TKEPIYIVTEYMARGc 319
Cdd:cd07843  16 GTYGVVYRARDKKTGEiVALKKLK---MEKEKegFpitsLREINILLKLQHPNIVTVKEVVvgsNLDKIYMVMEYVEHD- 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiidsEYtaqegaKFPI 399
Cdd:cd07843  92 LKSLMETMKQP-FLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAR----EY------GSPL 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 33469982 400 K---------W-TAPEAIhFG--VFTIKADVWSFGVLLMEVVT 430
Cdd:cd07843 161 KpytqlvvtlWyRAPELL-LGakEYSTAIDMWSVGCIFAELLT 202
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
279-482 2.22e-14

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: 73.23  E-value: 2.22e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 279 EAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLDFLKtDEGSrLSLPRLIDMSAQIAEGMAYIERMNSI 357
Cdd:cd06630  48 EAIREEIRMMARLNHPNIVRMLgATQHKSHFNIFVEWMAGGSVASLLS-KYGA-FSENVIINYTLQILRGLAYLHDNQII 125
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 358 HRDLRAANILV-SEALCCKIADFGLARIIDSEYTaqeGA-KF------PIKWTAPEAIHFGVFTIKADVWSFGVLLMEVV 429
Cdd:cd06630 126 HRDLKGANLLVdSTGQRLRIADFGAAARLASKGT---GAgEFqgqllgTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMA 202
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 430 TyGRVPYpgmsNPEVIRN-LERGYRM-------PRPDTCPPELyRGVIAECWRSRPEERPT 482
Cdd:cd06630 203 T-AKPPW----NAEKISNhLALIFKIasattppPIPEHLSPGL-RDVTLRCLELQPEDRPP 257
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
237-464 2.25e-14

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: 73.52  E-value: 2.25e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGYYKNNMK-VAIKTLK-EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTE 313
Cdd:cd06657  18 PRTYLDNFIKIGEGSTGIVCIATVKSSGKlVAVKKMDlRKQQRRELLFNEVVIMRDYQHENVVEMYnSYLVGDELWVVME 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTdegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE 393
Cdd:cd06657  98 FLEGGALTDIVTH---TRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRRK 174
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY---PGMSNPEVIRnlergyrmprpDTCPPEL 464
Cdd:cd06657 175 SLVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVD-GEPPYfnePPLKAMKMIR-----------DNLPPKL 236
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
244-461 2.40e-14

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 73.70  E-value: 2.40e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  244 VRKLGSGQFGEVWMGYYK-NNMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMArg 318
Cdd:PLN00009   7 VEKIGEGTYGVVYKARDRvTNETIALKKIRleqEDEGVPSTAIREISLLKEMQHGNIVRLQDVVHSEKrLYLVFEYLD-- 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  319 clLDFLK-TDEGSRLSL-PRLIDMSA-QIAEGMAYIERMNSIHRDLRAANILV---SEALccKIADFGLARIIDSEYTAQ 392
Cdd:PLN00009  85 --LDLKKhMDSSPDFAKnPRLIKTYLyQILRGIAYCHSHRVLHRDLKPQNLLIdrrTNAL--KLADFGLARAFGIPVRTF 160
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982  393 EGAKFPIKWTAPEaIHFGV--FTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERGYRMPRPDTCP 461
Cdd:PLN00009 161 THEVVTLWYRAPE-ILLGSrhYSTPVDIWSVGCIFAEMVNQ-KPLFPGDSEIDELFKIFRILGTPNEETWP 229
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
242-436 2.41e-14

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: 73.25  E-value: 2.41e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYY-KNNMKVAIK---------TLKEGTMSPEAFLG-------EANVMKALQHERLVRLYAVV- 303
Cdd:cd14077   4 EFVKTIGAGSMGKVKLAKHiRTGEKCAIKiiprasnagLKKEREKRLEKEISrdirtirEAALSSLLNHPHICRLRDFLr 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 TKEPIYIVTEYMARGCLLDF------LKTDEGSRLSLprlidmsaQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIA 377
Cdd:cd14077  84 TPNHYYMLFEYVDGGQLLDYiishgkLKEKQARKFAR--------QIASALDYLHRNSIVHRDLKIENILISKSGNIKII 155
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33469982 378 DFGLARIIDSEYTAQE--GAKFpikWTAPEAIHFGVFT-IKADVWSFGVLLMeVVTYGRVPY 436
Cdd:cd14077 156 DFGLSNLYDPRRLLRTfcGSLY---FAAPELLQAQPYTgPEVDVWSFGVVLY-VLVCGKVPF 213
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
247-430 2.53e-14

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: 72.74  E-value: 2.53e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEAFLGEANVMKALQ-HERLVRLYAVVTKEPIYIV--TEYMARGCLLD 322
Cdd:cd13987   1 LGEGTYGKVLLAVHKgSGTKMALKFVPKPSTKLKDFLREYNISLELSvHPHIIKTYDVAFETEDYYVfaQEYAPYGDLFS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC--CKIADFGLARIIDSEYTAQEGAkfpIK 400
Cdd:cd13987  81 IIPPQVG--LPEERVKRCAAQLASALDFMHSKNLVHRDIKPENVLLFDKDCrrVKLCDFGLTRRVGSTVKRVSGT---IP 155
                       170       180       190
                ....*....|....*....|....*....|....*
gi 33469982 401 WTAPE---AIHFGVFTIK--ADVWSFGVLLMEVVT 430
Cdd:cd13987 156 YTAPEvceAKKNEGFVVDpsIDVWAFGVLLFCCLT 190
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
243-482 2.96e-14

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: 72.85  E-value: 2.96e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYK-NNMKVAIKTL---KEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP--IYIVTEYMA 316
Cdd:cd08223   4 FLRVIGKGSYGEVWLVRHKrDRKQYVIKKLnlkNASKRERKAAEQEAKLLSKLKHPNIVSYKESFEGEDgfLYIVMGFCE 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEY---TAQE 393
Cdd:cd08223  84 GGDLYTRLKEQKGVLLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLESSSdmaTTLI 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLErGYRMPRPDTCPPELYRgVIAECW 473
Cdd:cd08223 164 GTPY---YMSPELFSNKPYNHKSDVWALGCCVYEMATLKHAFNAKDMNSLVYKILE-GKLPPMPKQYSPELGE-LIKAML 238

                ....*....
gi 33469982 474 RSRPEERPT 482
Cdd:cd08223 239 HQDPEKRPS 247
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
241-483 3.09e-14

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: 72.67  E-value: 3.09e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYK--------NNMKVAIKTLKEGTMS-PEAFLGEANVMKALQHERLVRLYAV-VTKEPIYI 310
Cdd:cd05078   1 LIFNESLGQGTFTKIFKGIRRevgdygqlHETEVLLKVLDKAHRNySESFFEAASMMSQLSHKHLVLNYGVcVCGDENIL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKTDEGSrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV--------SEALCCKIADFGLA 382
Cdd:cd05078  81 VQEYVKFGSLDTYLKKNKNC-INILWKLEVAKQLAWAMHFLEEKTLVHGNVCAKNILLireedrktGNPPFIKLSDPGIS 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSEYTAQEgakfPIKWTAPEAIHFGV-FTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCp 461
Cdd:cd05078 160 ITVLPKDILLE----RIPWVPPECIENPKnLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWT- 234
                       250       260
                ....*....|....*....|..
gi 33469982 462 pELyRGVIAECWRSRPEERPTF 483
Cdd:cd05078 235 -EL-ANLINNCMDYEPDHRPSF 254
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
117-219 3.57e-14

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: 68.58  E-value: 3.57e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 117 ESLEMERWFFRSQGRKEAErQLLAPINKAGSFLIRESETnKGAFSLSVKDVTTQGELIKHYKIRCLDEGGYYISPRITFP 196
Cdd:cd09934   1 LNLEKYEWYVGDMSRQRAE-SLLKQEDKEGCFVVRNSST-KGLYTVSLFTKVPGSPHVKHYHIKQNARSEFYLAEKHCFE 78
                        90       100
                ....*....|....*....|...
gi 33469982 197 SLQALVQHYSKKGDGLCQRLTLP 219
Cdd:cd09934  79 TIPELINYHQHNSGGLATRLKYP 101
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
247-472 3.69e-14

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: 73.49  E-value: 3.69e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM----SPEAFLGEANVMkALQHER--LVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd05616   8 LGKGSFGKVMLAERKGTDELyAVKILKKDVViqddDVECTMVEKRVL-ALSGKPpfLTQLHSCFqTMDRLYFVMEYVNGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLdfLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR--IIDSeYTAQEGAK 396
Cdd:cd05616  87 DLM--YHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKenIWDG-VTTKTFCG 163
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 397 FPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLergyrMPRPDTCPPELYRGVIAEC 472
Cdd:cd05616 164 TP-DYIAPEIIAYQPYGKSVDWWAFGVLLYEMLA-GQAPFEGEDEDELFQSI-----MEHNVAYPKSMSKEAVAIC 232
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
124-205 4.04e-14

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 68.07  E-value: 4.04e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 124 WFFRSQGRKEAERQLLAPINKaGSFLIRESETNKGAFSLSVKdvttQGELIKHYKIRCLDEGGYYISpRITFPSLQALVQ 203
Cdd:cd09941   5 WFHGKISRAEAEEILMNQRPD-GAFLIRESESSPGDFSLSVK----FGNDVQHFKVLRDGAGKYFLW-VVKFNSLNELVD 78

                ..
gi 33469982 204 HY 205
Cdd:cd09941  79 YH 80
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
258-492 4.31e-14

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: 72.28  E-value: 4.31e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 258 GYYKNNMKVAIKTLKEGTMSPE-AFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARGCLLDFLKTDEGSRLSLPR 336
Cdd:cd05077  31 YSYEKEIKVILKVLDPSHRDISlAFFETASMMRQVSHKHIVLLYGVCVRDVENIMVEEFVEFGPLDLFMHRKSDVLTTPW 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 337 LIDMSAQIAEGMAYIERMNSIHRDLRAANILVS----EALC---CKIADFGLARIIDSEYTAQEgakfPIKWTAPEAIH- 408
Cdd:cd05077 111 KFKVAKQLASALSYLEDKDLVHGNVCTKNILLAregiDGECgpfIKLSDPGIPITVLSRQECVE----RIPWIAPECVEd 186
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 409 FGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDtCpPELYRgVIAECWRSRPEERPtfeFLQS 488
Cdd:cd05077 187 SKNLSIAADKWSFGTTLWEICYNGEIPLKDKTLAEKERFYEGQCMLVTPS-C-KELAD-LMTHCMNYDPNQRP---FFRA 260

                ....
gi 33469982 489 VLED 492
Cdd:cd05077 261 IMRD 264
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
237-452 4.51e-14

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: 72.83  E-value: 4.51e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTE 313
Cdd:cd06656  17 PKKKYTRFEKIGQGASGTVYTAIdIATGQEVAIKQMNlQQQPKKELIINEILVMRENKNPNIVNyLDSYLVGDELWVVME 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLK---TDEGSRLSLPRlidmsaQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYT 390
Cdd:cd06656  97 YLAGGSLTDVVTetcMDEGQIAAVCR------ECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQS 170
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 391 AQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY-----------------PGMSNPEVIRNLERGY 452
Cdd:cd06656 171 KRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPYlnenplralyliatngtPELQNPERLSAVFRDF 248
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
237-452 4.75e-14

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: 72.83  E-value: 4.75e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTE 313
Cdd:cd06654  18 PKKKYTRFEKIGQGASGTVYTAMdVATGQEVAIRQMNlQQQPKKELIINEILVMRENKNPNIVNyLDSYLVGDELWVVME 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLK---TDEGSRLSLPRlidmsaQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYT 390
Cdd:cd06654  98 YLAGGSLTDVVTetcMDEGQIAAVCR------ECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQS 171
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 391 AQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY-----------------PGMSNPEVIRNLERGY 452
Cdd:cd06654 172 KRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIE-GEPPYlnenplralyliatngtPELQNPEKLSAIFRDF 249
SH3_SLAP-like cd11848
Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited ...
62-116 4.97e-14

Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. Vertebrates contain two SLAPs, named SLAP (or SLA1) and SLAP2 (or SLA2). SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, among others, while SLAP2 interacts with CSF1R. Both SLAPs interact with c-Cbl, LAT, CD247, and Zap70. SLAP modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. The SH3 domain of SLAP forms a complex with v-Abl. 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: 212782  Cd Length: 55  Bit Score: 66.44  E-value: 4.97e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVARV 116
Cdd:cd11848   1 TLVALGDYPSGGPAELSLRLGEPLTIVSDEGDWWKVLSEVTGRESYIPSVHVAKV 55
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
118-219 5.19e-14

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: 68.05  E-value: 5.19e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 118 SLEMERWFFRSQGRKEAERqLLAPINKAGSFLIRESeTNKGAFSLSV--KDVTTQGELIKHYKIRCLDEGGYYISPRITF 195
Cdd:cd10398   2 NLEIYEWYHKNITRNQAER-LLRQESKEGAFIVRDS-RHLGSYTISVftRARRSTEASIKHYQIKKNDSGQWYVAERHLF 79
                        90       100
                ....*....|....*....|....
gi 33469982 196 PSLQALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10398  80 QSIPELIQYHQHNAAGLMSRLRYP 103
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
237-487 5.36e-14

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: 72.45  E-value: 5.36e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLK-EGTMSPEAFLGEANVMKALQHERLVR-LYAVVTKEPIYIVTE 313
Cdd:cd06655  17 PKKKYTRYEKIGQGASGTVFTAIdVATGQEVAIKQINlQKQPKKELIINEILVMKELKNPNIVNfLDSFLVGDELFVVME 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLK---TDEGSRLSLPRlidmsaQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYT 390
Cdd:cd06655  97 YLAGGSLTDVVTetcMDEAQIAAVCR------ECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQS 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 391 AQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYpgmSNPEVIRNLERGYRMPRPDTCPPE----LYR 466
Cdd:cd06655 171 KRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY---LNENPLRALYLIATNGTPELQNPEklspIFR 246
                       250       260
                ....*....|....*....|..
gi 33469982 467 GVIAECWRSRPEERPTF-EFLQ 487
Cdd:cd06655 247 DFLNRCLEMDVEKRGSAkELLQ 268
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
246-491 5.64e-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: 71.96  E-value: 5.64e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGY-YKNNMKVA---IKTLKEGTMSPEAFLGEANVMKALQHERLVRLY-----AVVTKEPIYIVTEYMA 316
Cdd:cd14033   8 EIGRGSFKTVYRGLdTETTVEVAwceLQTRKLSKGERQRFSEEVEMLKGLQHPNIVRFYdswksTVRGHKCIILVTELMT 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGSRLSLprLIDMSAQIAEGMAYIERMNS--IHRDLRAANILVS-EALCCKIADFGLARIIDSEYtAQE 393
Cdd:cd14033  88 SGTLKTYLKRFREMKLKL--LQRWSRQILKGLHFLHSRCPpiLHRDLKCDNIFITgPTGSVKIGDLGLATLKRASF-AKS 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFPiKWTAPEaIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSN-PEVIRNLERGYrmpRPDTC----PPELyRGV 468
Cdd:cd14033 165 VIGTP-EFMAPE-MYEEKYDEAVDVYAFGMCILEMAT-SEYPYSECQNaAQIYRKVTSGI---KPDSFykvkVPEL-KEI 237
                       250       260
                ....*....|....*....|...
gi 33469982 469 IAECWRSRPEERPTfefLQSVLE 491
Cdd:cd14033 238 IEGCIRTDKDERFT---IQDLLE 257
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
241-448 5.70e-14

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: 73.13  E-value: 5.70e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM----SPEAFLGEANVM-KALQHERLVRL-YAVVTKEPIYIVTE 313
Cdd:cd05602   9 FHFLKVIGKGSFGKVLLARHKSDEKFyAVKVLQKKAIlkkkEEKHIMSERNVLlKNVKHPFLVGLhFSFQTTDKLYFVLD 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTDegsRLSL-PRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR-IIDSEYTA 391
Cdd:cd05602  89 YINGGELFYHLQRE---RCFLePRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKeNIEPNGTT 165
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 392 QEGAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVtYGRVPYPGMSNPEVIRNL 448
Cdd:cd05602 166 STFCGTP-EYLAPEVLHKQPYDRTVDWWCLGAVLYEML-YGLPPFYSRNTAEMYDNI 220
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
246-448 6.56e-14

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: 71.91  E-value: 6.56e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNN-MKVAIKTLKEGT-------MSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd14196  12 ELGSGQFAIVKKCREKSTgLEYAAKFIKKRQsrasrrgVSREEIEREVSILRQVLHPNIITLHDVYeNRTDVVLILELVS 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC----CKIADFGLAriidseYTAQ 392
Cdd:cd14196  92 GGELFDFLAQKES--LSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIpiphIKLIDFGLA------HEIE 163
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 393 EGAKFP-----IKWTAPEAIHFGVFTIKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNL 448
Cdd:cd14196 164 DGVEFKnifgtPEFVAPEIVNYEPLGLEADMWSIGVITY-ILLSGASPFLGDTKQETLANI 223
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
244-440 6.86e-14

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: 71.94  E-value: 6.86e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMK-VAIKTLK-----EGTmsPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMA 316
Cdd:cd07835   4 LEKIGEGTYGVVYKARDKLTGEiVALKKIRletedEGV--PSTAIREISLLKELNHPNIVRLLDVVHSENkLYLVFEFLD 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 rgclLDFLK-TDEGSRLSL-PRLIDM-SAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDseytaqe 393
Cdd:cd07835  82 ----LDLKKyMDSSPLTGLdPPLIKSyLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARAFG------- 150
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 gakFPIK---------W-TAPEaIHFGV--FTIKADVWSFGVLLMEVVTygRVP-YPGMS 440
Cdd:cd07835 151 ---VPVRtythevvtlWyRAPE-ILLGSkhYSTPVDIWSVGCIFAEMVT--RRPlFPGDS 204
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
237-486 9.67e-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: 71.61  E-value: 9.67e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRKLGSGQFGEVWMGYYKNNMKVA-IKTLK-EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTE 313
Cdd:cd06645   9 PQEDFELIQRIGSGTYGDVYKARNVNTGELAaIKVIKlEPGEDFAVVQQEIIMMKDCKHSNIVAYFgSYLRRDKLWICME 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTDegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQE 393
Cdd:cd06645  89 FCGGGSLQDIYHVT--GPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRK 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 394 GAKFPIKWTAPEAIHF---GVFTIKADVWSFGVLLMEVVTYgrvpYPGMSNPEVIRNLergYRMPRPDTCPPEL------ 464
Cdd:cd06645 167 SFIGTPYWMAPEVAAVerkGGYNQLCDIWAVGITAIELAEL----QPPMFDLHPMRAL---FLMTKSNFQPPKLkdkmkw 239
                       250       260
                ....*....|....*....|....*
gi 33469982 465 ---YRGVIAECWRSRPEERPTFEFL 486
Cdd:cd06645 240 snsFHHFVKMALTKNPKKRPTAEKL 264
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
239-479 1.11e-13

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: 71.60  E-value: 1.11e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWM-------GYYKNNMKVAIKTLKEGTmsPEAFLGEANVMKALQ---HERLVRLYAVVT---- 304
Cdd:cd07862   1 QQYECVAEIGEGAYGKVFKardlkngGRFVALKRVRVQTGEEGM--PLSTIREVAVLRHLEtfeHPNVVRLFDVCTvsrt 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 305 --KEPIYIVTEYMARGcLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd07862  79 drETKLTLVFEHVDQD-LTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLA 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIdSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVvtYGRVP-YPGMSNPEVIRNLERGYRMPRPDTCP 461
Cdd:cd07862 158 RIY-SFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEM--FRRKPlFRGSSDVDQLGKILDVIGLPGEEDWP 234
                       250
                ....*....|....*...
gi 33469982 462 PELyrGVIAECWRSRPEE 479
Cdd:cd07862 235 RDV--ALPRQAFHSKSAQ 250
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
239-428 1.41e-13

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: 71.32  E-value: 1.41e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGYYKNNmKVAIKTLKegTMSPEAFLGEANVMKA--LQHERLVRLYA--VVTKEP---IYIV 311
Cdd:cd14142   5 RQITLVECIGKGRYGEVWRGQWQGE-SVAVKIFS--SRDEKSWFRETEIYNTvlLRHENILGFIAsdMTSRNSctqLWLI 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEgsrLSLPRLIDMSAQIAEGMAY----IERMNS----IHRDLRAANILVSEALCCKIADFGLA- 382
Cdd:cd14142  82 THYHENGSLYDYLQRTT---LDHQEMLRLALSAASGLVHlhteIFGTQGkpaiAHRDLKSKNILVKSNGQCCIADLGLAv 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 383 ------RIIDSEYTAQEGAKfpiKWTAPEAIH-------FGVFTiKADVWSFGVLLMEV 428
Cdd:cd14142 159 thsqetNQLDVGNNPRVGTK---RYMAPEVLDetintdcFESYK-RVDIYAFGLVLWEV 213
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
61-113 1.75e-13

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: 64.85  E-value: 1.75e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 33469982  61 HFVVALYDYTAMNDRDLQMLKGEKLQVLK-GTGDWWLARSlVTGREGYVPSNFV 113
Cdd:cd11906   1 KKVVALYDYTPMNAQDLQLRKGEEYVILEeSNLPWWRARD-KNGREGYIPSNYV 53
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
64-110 1.80e-13

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: 64.53  E-value: 1.80e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 33469982    64 VALYDYTAMNDRDLQMLKGEKLQVL-KGTGDWWLARSLvTGREGYVPS 110
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLeKSEDGWWKGRNK-GGKEGLIPS 47
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
243-425 1.96e-13

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: 70.43  E-value: 1.96e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMK-VAIKTL-KEGTMSPEAFL-GEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd14095   4 IGRVIGDGNFAVVKECRDKATDKeYALKIIdKAKCKGKEHMIeNEVAILRRVKHPNIVQLIEEYdTDTELYLVMELVKGG 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSE----ALCCKIADFGLARIIDSeytaqeg 394
Cdd:cd14095  84 DLFDAIT--SSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVVEhedgSKSLKLADFGLATEVKE------- 154
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 33469982 395 akfPI-------KWTAPEAIHFGVFTIKADVWSFGVLL 425
Cdd:cd14095 155 ---PLftvcgtpTYVAPEILAETGYGLKVDIWAAGVIT 189
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
247-425 2.22e-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: 70.13  E-value: 2.22e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-VAIKT---LKEGTMSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMaRGCLL 321
Cdd:cd14082  11 LGSGQFGIVYGGKHRKTGRdVAIKVidkLRFPTKQESQLRNEVAILQQLSHPGVVNLECMFeTPERVFVVMEKL-HGDML 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC---CKIADFGLARIIDSEYTAQEGAKFP 398
Cdd:cd14082  90 EMILSSEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLASAEPfpqVKLCDFGFARIIGEKSFRRSVVGTP 169
                       170       180
                ....*....|....*....|....*..
gi 33469982 399 iKWTAPEAIHFGVFTIKADVWSFGVLL 425
Cdd:cd14082 170 -AYLAPEVLRNKGYNRSLDMWSVGVII 195
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
243-482 2.37e-13

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


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 70.01  E-value: 2.37e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEV-WMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCL 320
Cdd:cd14665   4 LVKDIGSGNFGVArLMRDKQTKELVAVKYIERGEKIDENVQREIINHRSLRHPNIVRFKEVIlTPTHLAIVMEYAAGGEL 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 ldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV--SEALCCKIADFGLAR--IIDSEYTAQEGAK 396
Cdd:cd14665  84 --FERICNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLdgSPAPRLKICDFGYSKssVLHSQPKSTVGTP 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 397 fpiKWTAPEAIHFGVFTIK-ADVWSFGVLLMeVVTYGRVPYPGMSNPE-----VIRNLERGYRMPRPDTCPPELyRGVIA 470
Cdd:cd14665 162 ---AYIAPEVLLKKEYDGKiADVWSCGVTLY-VMLVGAYPFEDPEEPRnfrktIQRILSVQYSIPDYVHISPEC-RHLIS 236
                       250
                ....*....|..
gi 33469982 471 ECWRSRPEERPT 482
Cdd:cd14665 237 RIFVADPATRIT 248
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
247-429 2.37e-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: 70.72  E-value: 2.37e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMgyYKN---NMKVAIKT--LKEGTMSPEAFLGEANVMKALQHERLVR-------LYAVVTKEPIyIVTEY 314
Cdd:cd14039   1 LGTGGFGNVCL--YQNqetGEKIAIKScrLELSVKNKDRWCHEIQIMKKLNHPNVVKacdvpeeMNFLVNDVPL-LAMEY 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFL-KTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA---LCCKIADFGLARIID--SE 388
Cdd:cd14039  78 CSGGDLRKLLnKPENCCGLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVLQEIngkIVHKIIDLGYAKDLDqgSL 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 33469982 389 YTAQEGAkfpIKWTAPEAIHFGVFTIKADVWSFGVLLMEVV 429
Cdd:cd14039 158 CTSFVGT---LQYLAPELFENKSYTVTVDYWSFGTMVFECI 195
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
246-438 2.39e-13

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: 70.78  E-value: 2.39e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKN---NMKVAIKTLK----EGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP---IYIVTEYm 315
Cdd:cd07842   7 CIGRGTYGRVYKAKRKNgkdGKEYAIKKFKgdkeQYTGISQSACREIALLRELKHENVVSLVEVFLEHAdksVYLLFDY- 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLK-TDEGSRLSLPRLIDMSA--QIAEGMAYIERMNSIHRDLRAANILV----SEALCCKIADFGLARIIDSe 388
Cdd:cd07842  86 AEHDLWQIIKfHRQAKRVSIPPSMVKSLlwQILNGIHYLHSNWVLHRDLKPANILVmgegPERGVVKIGDLGLARLFNA- 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 389 ytaqegakfPIK------------W-TAPE----AIHfgvFTIKADVWSFGVLLMEVVTYgRVPYPG 438
Cdd:cd07842 165 ---------PLKpladldpvvvtiWyRAPElllgARH---YTKAIDIWAIGCIFAELLTL-EPIFKG 218
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
123-222 2.47e-13

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


Pssm-ID: 198190  Cd Length: 98  Bit Score: 65.77  E-value: 2.47e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 123 RWFFRSQGRKEAERQLLAPinKAGSFLIRESETNKGAFSLSVkdvTTQGELIkHYKIrcldeggYYISPRIT------FP 196
Cdd:cd09937   4 PWFHGKISREEAERLLQPP--EDGLFLVRESTNYPGDYTLCV---SFEGKVE-HYRV-------IYRNGKLTideeeyFE 70
                        90       100
                ....*....|....*....|....*.
gi 33469982 197 SLQALVQHYSKKGDGLCQRLTLPCVR 222
Cdd:cd09937  71 NLIQLVEHYTKDADGLCTRLVKPKVK 96
pknD PRK13184
serine/threonine-protein kinase PknD;
239-462 2.71e-13

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 72.50  E-value: 2.71e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  239 QSLRLVRKLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMSPE----AFLGEANVMKALQHERLVRLYAVVT-KEPIYIVT 312
Cdd:PRK13184   2 QRYDIIRLIGKGGMGEVYLAYDPVcSRRVALKKIREDLSENPllkkRFLREAKIAADLIHPGIVPVYSICSdGDPVYYTM 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  313 EYMaRGCLL----------DFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV---SEALcckIADF 379
Cdd:PRK13184  82 PYI-EGYTLksllksvwqkESLSKELAEKTSVGAFLSIFHKICATIEYVHSKGVLHRDLKPDNILLglfGEVV---ILDW 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  380 GLARIIDSEYTAQEGAKFPIK------------------WTAPEAIHFGVFTIKADVWSFGVLLMEVVTygrvpypgMSN 441
Cdd:PRK13184 158 GAAIFKKLEEEDLLDIDVDERnicyssmtipgkivgtpdYMAPERLLGVPASESTDIYALGVILYQMLT--------LSF 229
                        250       260
                 ....*....|....*....|.
gi 33469982  442 PevIRNlERGYRMPRPDTCPP 462
Cdd:PRK13184 230 P--YRR-KKGRKISYRDVILS 247
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
292-482 3.26e-13

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


Pssm-ID: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 69.61  E-value: 3.26e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 292 QHERLVRLYAV-VTKEPIYIVTEYMArGCLLDFLKTDEGSRLSL---PRLIDMSAQIAEGMAYIERMNSIHRDLRAANIL 367
Cdd:cd13982  53 EHPNVIRYFCTeKDRQFLYIALELCA-ASLQDLVESPRESKLFLrpgLEPVRLLRQIASGLAHLHSLNIVHRDLKPQNIL 131
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 368 VS-----EALCCKIADFGLARIID---SEYTAQEGAKFPIKWTAPEAIHFGVF---TIKADVWSFGVLLMEVVTYGRVPY 436
Cdd:cd13982 132 IStpnahGNVRAMISDFGLCKKLDvgrSSFSRRSGVAGTSGWIAPEMLSGSTKrrqTRAVDIFSLGCVFYYVLSGGSHPF 211
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 437 PGMSNPEviRNLERG-YRMPRPD---TCPPELyRGVIAECWRSRPEERPT 482
Cdd:cd13982 212 GDKLERE--ANILKGkYSLDKLLslgEHGPEA-QDLIERMIDFDPEKRPS 258
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
237-496 3.62e-13

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: 69.58  E-value: 3.62e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 237 PRQSLRLVRK--LGSGQFG-----------EVWMGyyknnmKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVV 303
Cdd:cd14187   3 PRTRRRYVRGrfLGKGGFAkcyeitdadtkEVFAG------KIVPKSLLLKPHQKEKMSMEIAIHRSLAHQHVVGFHGFF 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 TKEP-IYIVTEYMARGCLLDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd14187  77 EDNDfVYVVLELCRRRSLLELHKRRKA--LTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLA 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEV-IRNLERGYRMPRPDTcp 461
Cdd:cd14187 155 TKVEYDGERKKTLCGTPNYIAPEVLSKKGHSFEVDIWSIGCIMYTLLV-GKPPFETSCLKETyLRIKKNEYSIPKHIN-- 231
                       250       260       270
                ....*....|....*....|....*....|....*
gi 33469982 462 pELYRGVIAECWRSRPEERPTFEFLQSvlEDFYTA 496
Cdd:cd14187 232 -PVAASLIQKMLQTDPTARPTINELLN--DEFFTS 263
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
245-491 3.70e-13

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: 69.46  E-value: 3.70e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEAFLG-----EANVMKALQHERLVRLYAVV-TKEPIYIVTEYMAR 317
Cdd:cd14070   8 RKLGEGSFAKVREGLHAvTGEKVAIKVIDKKKAKKDSYVTknlrrEGRIQQMIRHPNITQLLDILeTENSYYLVMELCPG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDflKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGL---ARII--DSEYTAQ 392
Cdd:cd14070  88 GNLMH--RIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLsncAGILgySDPFSTQ 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 393 EGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYpgMSNPEVIRNLERGYRMPRPDTCPPELYRGVIaec 472
Cdd:cd14070 166 CGSP---AYAAPELLARKKYGPKVDVWSIGVNMYAMLT-GTLPF--TVEPFSLRALHQKMVDKEMNPLPTDLSPGAI--- 236
                       250
                ....*....|....*....
gi 33469982 473 wrsrpeerptfEFLQSVLE 491
Cdd:cd14070 237 -----------SFLRSLLE 244
SH3_SLAP2 cd12011
Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent ...
64-116 3.86e-13

Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. It has been shown to interact with CSF1R, c-Cbl, LAT, CD247, and Zap70. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. The SH3 domain of SLAP forms a complex with v-Abl. 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: 212944  Cd Length: 55  Bit Score: 63.99  E-value: 3.86e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 33469982  64 VALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVARV 116
Cdd:cd12011   3 VALCNFPSGGPTELSIRMGEQLTILSEDGDWWKVSSAVTGRECYIPSNYVAKV 55
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
295-450 3.98e-13

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: 69.58  E-value: 3.98e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 295 RLVRLYAVV-TKEPIYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV-SEAL 372
Cdd:cd14197  70 WVINLHEVYeTASEMILVLEYAAGGEIFNQCVADREEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLtSESP 149
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 373 C--CKIADFGLARIIDSEYTAQEGAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLER 450
Cdd:cd14197 150 LgdIKIVDFGLSRILKNSEELREIMGTP-EYVAPEILSYEPISTATDMWSIGVLAYVMLT-GISPFLGDDKQETFLNISQ 227
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
246-448 4.05e-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: 69.65  E-value: 4.05e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNN-MKVAIKTLKEGTMSP-------EAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd14195  12 ELGSGQFAIVRKCREKGTgKEYAAKFIKKRRLSSsrrgvsrEEIEREVNILREIQHPNIITLHDIFeNKTDVVLILELVS 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALC----CKIADFGLARIIDSEYTAQ 392
Cdd:cd14195  92 GGELFDFLAEKES--LTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVpnprIKLIDFGIAHKIEAGNEFK 169
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 393 EGAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNL 448
Cdd:cd14195 170 NIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITY-ILLSGASPFLGETKQETLTNI 223
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
123-228 4.20e-13

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


Pssm-ID: 198191  Cd Length: 104  Bit Score: 65.49  E-value: 4.20e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 123 RWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVkdvtTQGELIKHYKIRCLDEGGYYISPRITFPSLQALV 202
Cdd:cd09938   2 PFFYGSITREEAEEYLKLAGMSDGLFLLRQSLRSLGGYVLSV----CHGRKFHHYTIERQLNGTYAIAGGKAHCGPAELC 77
                        90       100
                ....*....|....*....|....*.
gi 33469982 203 QHYSKKGDGLCQRLTLPCVRPAPQNP 228
Cdd:cd09938  78 EYHSTDLDGLVCLLRKPCNRPPGVEP 103
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
247-442 4.29e-13

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: 69.78  E-value: 4.29e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEV--WMgYYKNNMKVAIKTLK-EGTMSP---EAFLGEANVMKALQHERLVRlyAVVTKEPIYIVT-------- 312
Cdd:cd13989   1 LGSGGFGYVtlWK-HQDTGEYVAIKKCRqELSPSDknrERWCLEVQIMKKLNHPNVVS--ARDVPPELEKLSpndlplla 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 313 -EYMARGCLLDFLKTDEG-SRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA---LCCKIADFGLARIID- 386
Cdd:cd13989  78 mEYCSGGDLRKVLNQPENcCGLKESEVRTLLSDISSAISYLHENRIIHRDLKPENIVLQQGggrVIYKLIDLGYAKELDq 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 387 -SEYTAQEGAkfpIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNP 442
Cdd:cd13989 158 gSLCTSFVGT---LQYLAPELFESKKYTCTVDYWSFGTLAFECIT-GYRPFLPNWQP 210
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
243-450 4.31e-13

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


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 69.15  E-value: 4.31e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYK--NNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGC 319
Cdd:cd14114   6 ILEELGTGAFGVVHRCTERatGNNFAAKFIMTPHESDKETVRKEIQIMNQLHHPKLINLHdAFEDDNEMVLILEFLSGGE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVS--EALCCKIADFGLARIIDSEYTAQ---EG 394
Cdd:cd14114  86 LFERI-AAEHYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTtkRSNEVKLIDFGLATHLDPKESVKvttGT 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 33469982 395 AKFpikwTAPEAIH---FGVFTikaDVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNLER 450
Cdd:cd14114 165 AEF----AAPEIVErepVGFYT---DMWAVGVLSY-VLLSGLSPFAGENDDETLRNVKS 215
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
243-480 4.97e-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: 69.12  E-value: 4.97e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEA----FLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMA 316
Cdd:cd14117  10 IGRPLGKGKFGNVYLAREKqSKFIVALKVLFKSQIEKEGvehqLRREIEIQSHLRHPNILRLYNYFhDRKRIYLILEYAP 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAriIDSEYTAQEGAK 396
Cdd:cd14117  90 RGELYKELQKHG--RFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWS--VHAPSLRRRTMC 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 397 FPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLER-GYRMPRpdtCPPELYRGVIAECWRS 475
Cdd:cd14117 166 GTLDYLPPEMIEGRTHDEKVDLWCIGVLCYELLV-GMPPFESASHTETYRRIVKvDLKFPP---FLSDGSRDLISKLLRY 241

                ....*
gi 33469982 476 RPEER 480
Cdd:cd14117 242 HPSER 246
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
242-455 5.13e-13

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


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 68.86  E-value: 5.13e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEgTMSPEAFLG-----EANVMKALQHERLVRLYAVV--TKEPIYIVTE 313
Cdd:cd14163   3 QLGKTIGEGTYSKVKEAFsKKHQRKVAIKIIDK-SGGPEEFIQrflprELQIVERLDHKNIIHVYEMLesADGKIYLVME 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVsEALCCKIADFGLARIIDSEYTaQE 393
Cdd:cd14163  82 LAEDGDVFDCVL--HGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALL-QGFTLKLTDFGFAKQLPKGGR-EL 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 394 GAKF--PIKWTAPEAIHfGV--FTIKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNLERGYRMP 455
Cdd:cd14163 158 SQTFcgSTAYAAPEVLQ-GVphDSRKGDIWSMGVVLY-VMLCAQLPFDDTDIPKMLCQQQKGVSLP 221
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
245-436 5.17e-13

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


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 69.94  E-value: 5.17e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM----SPEAFLGEANVMK-ALQHERLVRLYAVV-TKEPIYIVTEYMAR 317
Cdd:cd05590   1 RVLGKGSFGKVMLARLKESGRLyAVKVLKKDVIlqddDVECTMTEKRILSlARNHPFLTQLYCCFqTPDRLFFVMEFVNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLdfLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR--IIDSEYTAQEGA 395
Cdd:cd05590  81 GDLM--FHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKegIFNGKTTSTFCG 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 33469982 396 KfPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05590 159 T-P-DYIAPEILQEMLYGPSVDWWAMGVLLYEMLC-GHAPF 196
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
245-425 5.31e-13

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


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 68.82  E-value: 5.31e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKN-NMKVAIKTLKEGTMSPEAFLGEANVM--KALQHERLVRLYAVV-TKEPIYIVTEYMARGCL 320
Cdd:cd14185   6 RTIGDGNFAVVKECRHWNeNQEYAMKIIDKSKLKGKEDMIESEILiiKSLSHPNIVKLFEVYeTEKEIYLILEYVRGGDL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVS----EALCCKIADFGLARIIDSEYTAQEGAK 396
Cdd:cd14185  86 FDAII--ESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQhnpdKSTTLKLADFGLAKYVTGPIFTVCGTP 163
                       170       180
                ....*....|....*....|....*....
gi 33469982 397 fpiKWTAPEAIHFGVFTIKADVWSFGVLL 425
Cdd:cd14185 164 ---TYVAPEILSEKGYGLEVDMWAAGVIL 189
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
238-428 6.38e-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: 69.06  E-value: 6.38e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 238 RQSLRLVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKegtMSPEAFLGEANVMKALQHERLVRLY---------------- 300
Cdd:cd14047   5 RQDFKEIELIGSGGFGQVFKAKHRIDGKTyAIKRVK---LNNEKAEREVKALAKLDHPNIVRYNgcwdgfdydpetsssn 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 301 -AVVTKEPIYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADF 379
Cdd:cd14047  82 sSRSKTKCLFIQMEFCEKGTLESWIEKRNGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDF 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 33469982 380 GL--ARIIDSEYTAQEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEV 428
Cdd:cd14047 162 GLvtSLKNDGKRTKSKGTL---SYMSPEQISSQDYGKEVDIYALGLILFEL 209
SH3_Eps8 cd11764
Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar ...
62-113 6.46e-13

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: 63.05  E-value: 6.46e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSlVTGREGYVPSNFV 113
Cdd:cd11764   1 YVRVLYDFTARNSKELSVLKGEYLEVLDDSRQWWKVRN-SRGQVGYVPHNIL 51
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
247-448 7.66e-13

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: 69.64  E-value: 7.66e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM----SPEAFLGEANVMkALQHER--LVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd05615  18 LGKGSFGKVMLAERKGSDELyAIKILKKDVViqddDVECTMVEKRVL-ALQDKPpfLTQLHSCFqTVDRLYFVMEYVNGG 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR--IIDSeYTAQEGAK 396
Cdd:cd05615  97 DLMYHIQ--QVGKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCKehMVEG-VTTRTFCG 173
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982 397 FPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNL 448
Cdd:cd05615 174 TP-DYIAPEIIAYQPYGRSVDWWAYGVLLYEMLA-GQPPFDGEDEDELFQSI 223
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
232-486 8.02e-13

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: 68.87  E-value: 8.02e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 232 DEWEIprqslrlVRKLGSGQFGEVW-MGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKAL-QHERLVRLYAVVTKE--- 306
Cdd:cd06639  22 DTWDI-------IETIGKGTYGKVYkVTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLpNHPNVVKFYGMFYKAdqy 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 ---PIYIVTEYMARGCLLDFLKT--DEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGL 381
Cdd:cd06639  95 vggQLWLVLELCNGGSVTELVKGllKCGQRLDEAMISYILYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGV 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 382 -ARIIDSEYTAQEGAKFPIkWTAPEAI-----HFGVFTIKADVWSFGVLLMEVVTYGrvpyPGMSNPEVIRNLERGYRMP 455
Cdd:cd06639 175 sAQLTSARLRRNTSVGTPF-WMAPEVIaceqqYDYSYDARCDVWSLGITAIELADGD----PPLFDMHPVKALFKIPRNP 249
                       250       260       270
                ....*....|....*....|....*....|....*
gi 33469982 456 RPDTCPPELY-RG---VIAECWRSRPEERPTFEFL 486
Cdd:cd06639 250 PPTLLNPEKWcRGfshFISQCLIKDFEKRPSVTHL 284
STKc_SRPK cd14136
Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze ...
242-430 8.40e-13

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: 69.14  E-value: 8.40e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPEAFLGEANVMKAL--------QHERLVRLY-AVVTKEP---- 307
Cdd:cd14136  13 HVVRKLGWGHFSTVWLCWDLQNKRfVALKVVKSAQHYTEAALDEIKLLKCVreadpkdpGREHVVQLLdDFKHTGPngth 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMarGC-LLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNS-IHRDLRAANILVSEA-LCCKIADFGLARI 384
Cdd:cd14136  93 VCMVFEVL--GPnLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGiIHTDIKPENVLLCISkIEVKIADLGNACW 170
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982 385 IDSEYTAQegakfpIK---WTAPEAI---HFGVftiKADVWSFGVLLMEVVT 430
Cdd:cd14136 171 TDKHFTED------IQtrqYRSPEVIlgaGYGT---PADIWSTACMAFELAT 213
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
282-431 9.67e-13

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 69.52  E-value: 9.67e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  282 LGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARGCLLDFLkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDL 361
Cdd:PHA03209 105 LIEAMLLQNVNHPSVIRMKDTLVSGAITCMVLPHYSSDLYTYL-TKRSRPLPIDQALIIEKQILEGLRYLHAQRIIHRDV 183
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33469982  362 RAANILVSEALCCKIADFGLAR--IIDSEYTAQEGAkfpIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTY 431
Cdd:PHA03209 184 KTENIFINDVDQVCIGDLGAAQfpVVAPAFLGLAGT---VETNAPEVLARDKYNSKADIWSAGIVLFEMLAY 252
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
250-451 1.00e-12

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: 68.28  E-value: 1.00e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 250 GQFGEVWMGYYKNNMK-VAIKTLKEGTMSPE-----AFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCLLD 322
Cdd:cd05611   7 GAFGSVYLAKKRSTGDyFAIKVLKKSDMIAKnqvtnVKAERAIMMIQGESPYVAKLYYSFqSKDYLYLVMEYLNGGDCAS 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIdseYTAQEGAKF---Pi 399
Cdd:cd05611  87 LIKTLGG--LPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNG---LEKRHNKKFvgtP- 160
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 33469982 400 KWTAPEAIhFGVFTIKA-DVWSFGVLLMEVVtYGRVPYPGMSNPEVIRNLERG 451
Cdd:cd05611 161 DYLAPETI-LGVGDDKMsDWWSLGCVIFEFL-FGYPPFHAETPDAVFDNILSR 211
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
247-424 1.29e-12

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: 68.13  E-value: 1.29e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-VAIKTL-------KEGTMSpeaflGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMAR 317
Cdd:cd14167  11 LGTGAFSEVVLAEEKRTQKlVAIKCIakkalegKETSIE-----NEIAVLHKIKHPNIVALDDIYeSGGHLYLIMQLVSG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLD------FLKTDEGSRLSlprlidmsAQIAEGMAYIERMNSIHRDLRAANIL---VSEALCCKIADFGLARIIDSE 388
Cdd:cd14167  86 GELFDrivekgFYTERDASKLI--------FQILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSKIEGSG 157
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 33469982 389 YTAQEGAKFPiKWTAPEAIHFGVFTIKADVWSFGVL 424
Cdd:cd14167 158 SVMSTACGTP-GYVAPEVLAQKPYSKAVDCWSIGVI 192
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
247-491 1.36e-12

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: 67.99  E-value: 1.36e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNnMKVAIKTLK-EGTMSPEA----FLGEANVMKALQHERLVRLYAVVTK-EPIYIVTEYMARGCL 320
Cdd:cd14160   1 IGEGEIFEVYRVRIGN-RSYAVKLFKqEKKMQWKKhwkrFLSELEVLLLFQHPNILELAAYFTEtEKFCLVYPYMQNGTL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFL-KTDEGSRLSLPRLIDMSAQIAEGMAYIERMNS---IHRDLRAANILVSEALCCKIADFGLARI----IDSEYT-A 391
Cdd:cd14160  80 FDRLqCHGVTKPLSWHERINILIGIAKAIHYLHNSQPctvICGNISSANILLDDQMQPKLTDFALAHFrphlEDQSCTiN 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKFPIKWTAPEA-IHFGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSN---PEVIRNL--ERG------YRMPRPDT 459
Cdd:cd14160 160 MTTALHKHLWYMPEEyIRQGKLSVKTDVYSFGIVIMEVLTGCKVVLDDPKHlqlRDLLHELmeKRGldsclsFLDLKFPP 239
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 33469982 460 CPP----ELYRgVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14160 240 CPRnfsaKLFR-LAGRCTATKAKLRPDMDEVLQRLE 274
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
239-438 1.44e-12

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 68.59  E-value: 1.44e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVrklGSGQFGEVWMGYY-KNNMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP------- 307
Cdd:cd07850   3 QNLKPI---GSGAQGIVCAAYDtVTGQNVAIKKLSrpfQNVTHAKRAYRELVLMKLVNHKNIIGLLNVFTPQKsleefqd 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYM-ARGCLLDFLKTDEgSRLSLprlidMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID 386
Cdd:cd07850  80 VYLVMELMdANLCQVIQMDLDH-ERMSY-----LLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAG 153
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 387 SEYTAQegakfPIKWT----APEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd07850 154 TSFMMT-----PYVVTryyrAPEVILGMGYKENVDIWSVGCIMGEMIR-GTVLFPG 203
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
245-436 1.47e-12

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


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 68.01  E-value: 1.47e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNN------MKVAIKTLKEGTMSPEAFLgEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMAR 317
Cdd:cd05607   8 RVLGKGGFGEVCAVQVKNTgqmyacKKLDKKRLKKKSGEKMALL-EKEILEKVNSPFIVSLaYAFETKTHLCLVMSLMNG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLlDFLKTDEGSR-LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYTAQE-G 394
Cdd:cd05607  87 GDL-KYHIYNVGERgIEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLAvEVKEGKPITQRaG 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 33469982 395 AKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05607 166 TN---GYMAPEILKEESYSYPVDWFAMGCSIYEMVA-GRTPF 203
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
62-112 1.49e-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: 1.49e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVL-KGTGDWWLARsLVTGREGYVPSNF 112
Cdd:cd00174   1 YARALYDYEAQDDDELSFKKGDIITVLeKDDDGWWEGE-LNGGREGLFPANY 51
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
235-481 1.55e-12

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: 68.54  E-value: 1.55e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLY-AVVTKEPIYI 310
Cdd:cd06650   1 ELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPairNQIIRELQVLHECNSPYIVGFYgAFYSDGEISI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYI-ERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSE 388
Cdd:cd06650  81 CMEHMDGGSLDQVLK--KAGRIPEQILGKVSIAVIKGLTYLrEKHKIMHRDVKPSNILVNSRGEIKLCDFGVSgQLIDSM 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPgmsnPEVIRNLErgyrmpRPDTCPPElyRGV 468
Cdd:cd06650 159 ANSFVGTR---SYMSPERLQGTHYSVQSDIWSMGLSLVEMAV-GRYPIP----PPDAKELE------LMFGCQVE--GDA 222
                       250
                ....*....|...
gi 33469982 469 IAECWRSRPEERP 481
Cdd:cd06650 223 AETPPRPRTPGRP 235
STKc_MRCK_beta cd05624
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control ...
233-493 1.60e-12

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


Pssm-ID: 270774 [Multi-domain]  Cd Length: 409  Bit Score: 69.27  E-value: 1.60e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 233 EWEIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPEA----FLGEANVMKALQHERLVRL-YAVVTKE 306
Cdd:cd05624  66 EMQLHRDDFEIIKVIGRGAFGEVAVVKMKNTERIyAMKILNKWEMLKRAetacFREERNVLVNGDCQWITTLhYAFQDEN 145
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 307 PIYIVTEYMARGCLLDFLKTDEGSrlsLPRliDMS----AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA 382
Cdd:cd05624 146 YLYLVMDYYVGGDLLTLLSKFEDK---LPE--DMArfyiGEMVLAIHSIHQLHYVHRDIKPDNVLLDMNGHIRLADFGSC 220
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSEYTAQEGAKFPI-KWTAPEAIH-----FGVFTIKADVWSFGVLLMEVVtYGRVPYPGMSNPEV---IRNLERGYR 453
Cdd:cd05624 221 LKMNDDGTVQSSVAVGTpDYISPEILQamedgMGKYGPECDWWSLGVCMYEML-YGETPFYAESLVETygkIMNHEERFQ 299
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 33469982 454 MPRPDTCPPELYRGVIAE--CWRSRpeerptfEFLQSVLEDF 493
Cdd:cd05624 300 FPSHVTDVSEEAKDLIQRliCSRER-------RLGQNGIEDF 334
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
120-208 1.78e-12

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


Pssm-ID: 198186  Cd Length: 104  Bit Score: 63.44  E-value: 1.78e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 120 EMERWFFRSQGRKEAErQLLAPINKAGSFLIRESETNKGAFSLSVKdvtTQGElIKHYKIRclDEGGYYISPRITFPSLQ 199
Cdd:cd09932   2 ESKEWFHANLTREQAE-EMLMRVPRDGAFLVRPSETDPNSFAISFR---AEGK-IKHCRIK--QEGRLFVIGTSQFESLV 74

                ....*....
gi 33469982 200 ALVQHYSKK 208
Cdd:cd09932  75 ELVSYYEKH 83
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
357-482 1.81e-12

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 69.51  E-value: 1.81e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  357 IHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKF---PIkWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYGR 433
Cdd:PTZ00283 165 IHRDIKSANILLCSNGLVKLGDFGFSKMYAATVSDDVGRTFcgtPY-YVAPEIWRRKPYSKKADMFSLGVLLYELLTLKR 243
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 33469982  434 vPYPGMSNPEVIRNLERGYRMPRPDTCPPELyRGVIAECWRSRPEERPT 482
Cdd:PTZ00283 244 -PFDGENMEEVMHKTLAGRYDPLPPSISPEM-QEIVTALLSSDPKRRPS 290
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
246-430 1.83e-12

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: 68.07  E-value: 1.83e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNN-MKVAIKTLKEgTMSP---EAFLGEANVMKALQHERLVR-------LYAVVTKEPIYIVTEY 314
Cdd:cd14038   1 RLGTGGFGNVLRWINQETgEQVAIKQCRQ-ELSPknrERWCLEIQIMKRLNHPNVVAardvpegLQKLAPNDLPLLAMEY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLDFLKTDEGS-RLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEA---LCCKIADFGLARIID--SE 388
Cdd:cd14038  80 CQGGDLRKYLNQFENCcGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQQGeqrLIHKIIDLGYAKELDqgSL 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 33469982 389 YTAQEGAkfpIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd14038 160 CTSFVGT---LQYLAPELLEQQKYTVTVDYWSFGTLAFECIT 198
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
239-429 2.00e-12

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 68.47  E-value: 2.00e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  239 QSLRLVRKLGSGQFGEVWMGYYKNN--MKVAIKTLKEGTM----SPEAFLGEANVMKALQHERLVRLYAVVTKEP-IYIV 311
Cdd:PTZ00426  30 EDFNFIRTLGTGSFGRVILATYKNEdfPPVAIKRFEKSKIikqkQVDHVFSERKILNYINHPFCVNLYGSFKDESyLYLV 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  312 TEYMARGCLLDFLKTDEgsrlSLPRLID--MSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEY 389
Cdd:PTZ00426 110 LEFVIGGEFFTFLRRNK----RFPNDVGcfYAAQIVLIFEYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKVVDTRT 185
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 33469982  390 TAQEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVV 429
Cdd:PTZ00426 186 YTLCGTP---EYIAPEILLNVGHGKAADWWTLGIFIYEIL 222
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
243-440 2.02e-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: 68.16  E-value: 2.02e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGY-YKNNMKVAIKTLkegtmsPEAF---------LGEANVMKALQHERLVRLYAVV-TKEP---- 307
Cdd:cd07855   9 PIETIGSGAYGVVCSAIdTKSGQKVAIKKI------PNAFdvvttakrtLRELKILRHFKHDNIIAIRDILrPKVPyadf 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 --IYIVTEYMaRGCLLDFLKTDEGsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII 385
Cdd:cd07855  83 kdVYVVLDLM-ESDLHHIIHSDQP--LTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARGL 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 33469982 386 DSE------YTAQEGAKFPikWTAPEAI-HFGVFTIKADVWSFGVLLMEVVtyGRVP-YPGMS 440
Cdd:cd07855 160 CTSpeehkyFMTEYVATRW--YRAPELMlSLPEYTQAIDMWSVGCIFAEML--GRRQlFPGKN 218
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
262-438 2.08e-12

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 68.17  E-value: 2.08e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 262 NNMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLYAVVTK------EPIYIVTEYMargclldflKTDegsrl 332
Cdd:cd07858  29 TNEKVAIKKIAnafDNRIDAKRTLREIKLLRHLDHENVIAIKDIMPPphreafNDVYIVYELM---------DTD----- 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 333 sLPRLIDMSA------------QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiidseyTAQEGAKFPIK 400
Cdd:cd07858  95 -LHQIIRSSQtlsddhcqyflyQLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLAR------TTSEKGDFMTE 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 33469982 401 ------WTAPEAI-HFGVFTIKADVWSFGVLLMEVVtyGRVP-YPG 438
Cdd:cd07858 168 yvvtrwYRAPELLlNCSEYTTAIDVWSVGCIFAELL--GRKPlFPG 211
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
247-436 2.16e-12

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270729 [Multi-domain]  Cd Length: 278  Bit Score: 67.55  E-value: 2.16e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTL-------KEG-TMSpeafLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMA 316
Cdd:cd05577   1 LGRGGFGEVCACQVKATGKMyACKKLdkkrikkKKGeTMA----LNEKIILEKVSSPFIVSLaYAFETKDKLCLVLTLMN 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAK 396
Cdd:cd05577  77 GGDLKYHIYNVGTRGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAVEFKGGKKIKGRVG 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 33469982 397 FPiKWTAPEAIHFGV-FTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05577 157 TH-GYMAPEVLQKEVaYDFSVDWFALGCMLYEMIA-GRSPF 195
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
247-429 2.50e-12

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: 67.21  E-value: 2.50e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNM-KVAIK--TLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEP------------IYIV 311
Cdd:cd14048  14 LGRGGFGVVFEAKNKVDDcNYAVKriRLPNNELAREKVLREVRALAKLDHPGIVRYFNAWLERPpegwqekmdevyLYIQ 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFL---KTDEGSRLSLprLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID-- 386
Cdd:cd14048  94 MQLCRKENLKDWMnrrCTMESRELFV--CLNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVTAMDqg 171
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 387 -------------SEYTAQEGAKFpikWTAPEAIHFGVFTIKADVWSFGVLLMEVV 429
Cdd:cd14048 172 epeqtvltpmpayAKHTGQVGTRL---YMSPEQIHGNQYSEKVDIFALGLILFELI 224
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
308-437 2.76e-12

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: 67.46  E-value: 2.76e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSI-HRDLRAANILVSEALCCKIADFGLA-RII 385
Cdd:cd06615  74 ISICMEHMDGGSLDQVLK--KAGRIPENILGKISIAVLRGLTYLREKHKImHRDVKPSNILVNSRGEIKLCDFGVSgQLI 151
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982 386 DSEYTAQEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYP 437
Cdd:cd06615 152 DSMANSFVGTR---SYMSPERLQGTHYTVQSDIWSLGLSLVEMAI-GRYPIP 199
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
247-462 2.76e-12

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: 67.68  E-value: 2.76e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM----SPEAFLGEANVM-KALQHERLVRL-YAVVTKEPIYIVTEYMARGC 319
Cdd:cd05604   4 IGKGSFGKVLLAKRKRDGKYyAVKVLQKKVIlnrkEQKHIMAERNVLlKNVKHPFLVGLhYSFQTTDKLYFVLDFVNGGE 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI-IDSEYTAQEGAKFP 398
Cdd:cd05604  84 L--FFHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCKEgISNSDTTTTFCGTP 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33469982 399 iKWTAPEAIHFGVFTIKADVWSFGVLLMEVVtYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPP 462
Cdd:cd05604 162 -EYLAPEVIRKQPYDNTVDWWCLGSVLYEML-YGLPPFYCRDTAEMYENILHKPLVLRPGISLT 223
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
242-430 2.99e-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: 66.91  E-value: 2.99e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVW-MGYYKNNMKVAIKTLKEGTMSPEAF--LGEANVMKALQ-HERLVRLYAVVTKEP---IYIVTEY 314
Cdd:cd07831   2 KILGKIGEGTFSEVLkAQSRKTGKYYAIKCMKKHFKSLEQVnnLREIQALRRLSpHPNILRLIEVLFDRKtgrLALVFEL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MaRGCLLDFLKtdeGSRLSLP--RLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEAlCCKIADFGLARIIDS----- 387
Cdd:cd07831  82 M-DMNLYELIK---GRKRPLPekRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKDD-ILKLADFGSCRGIYSkppyt 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 33469982 388 EYTAQegakfpiKW-TAPEAI-HFGVFTIKADVWSFGVLLMEVVT 430
Cdd:cd07831 157 EYIST-------RWyRAPECLlTDGYYGPKMDIWAVGCVFFEILS 194
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
243-425 3.14e-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: 67.06  E-value: 3.14e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPEAFLG---EANVMKALQHERLVRLYAVVTKEPI-YIVTEYMAR 317
Cdd:cd14086   5 LKEELGKGAFSVVRRCVQKSTGQEfAAKIINTKKLSARDHQKlerEARICRLLKHPNIVRLHDSISEEGFhYLVFDLVTG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTDEGSRLSlprliDMSA---QIAEGMAYIERMNSIHRDLRAANILV---SEALCCKIADFGLARIIDSEYTA 391
Cdd:cd14086  85 GELFEDIVAREFYSEA-----DASHciqQILESVNHCHQNGIVHRDLKPENLLLaskSKGAAVKLADFGLAIEVQGDQQA 159
                       170       180       190
                ....*....|....*....|....*....|....
gi 33469982 392 QEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLL 425
Cdd:cd14086 160 WFGFAGTPGYLSPEVLRKDPYGKPVDIWACGVIL 193
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
247-480 3.63e-12

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: 67.34  E-value: 3.63e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTL-KEGTMSPEAF---LGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMARGCL 320
Cdd:cd05595   3 LGKGTFGKVILVREKaTGRYYAMKILrKEVIIAKDEVahtVTESRVLQNTRHPFLTALkYAFQTHDRLCFVMEYANGGEL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLK-----TDEGSRLslprlidMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI-IDSEYTAQEG 394
Cdd:cd05595  83 FFHLSrervfTEDRARF-------YGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEgITDGATMKTF 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRN-LERGYRMPRpdTCPPELyRGVIAECW 473
Cdd:cd05595 156 CGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHERLFELiLMEEIRFPR--TLSPEA-KSLLAGLL 230

                ....*..
gi 33469982 474 RSRPEER 480
Cdd:cd05595 231 KKDPKQR 237
STKc_TTBK cd14017
Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the ...
244-491 3.74e-12

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270919 [Multi-domain]  Cd Length: 263  Bit Score: 66.51  E-value: 3.74e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGY-YKNNMKVAIKTlkEGTMSPEAFLG-EANVMKALQHERLV-RLYAV-VTKEPIYIVTEYMARGc 319
Cdd:cd14017   5 VKKIGGGGFGEIYKVRdVVDGEEVAMKV--ESKSQPKQVLKmEVAVLKKLQGKPHFcRLIGCgRTERYNYIVMTLLGPN- 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANIL--VSEALC--CKIADFGLARiidsEYTAQEGA 395
Cdd:cd14017  82 LAELRRSQPRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAigRGPSDErtVYILDFGLAR----QYTNKDGE 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 kfpIKWTAPEAIHF-GVF---TIKA----------DVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERGYRMPRP-DTC 460
Cdd:cd14017 158 ---VERPPRNAAGFrGTVryaSVNAhrnkeqgrrdDLWSWFYMLIEFVT-GQLPWRKLKDKEEVGKMKEKIDHEELlKGL 233
                       250       260       270
                ....*....|....*....|....*....|..
gi 33469982 461 PPELyrGVIAECWRSRP-EERPTFEFLQSVLE 491
Cdd:cd14017 234 PKEF--FQILKHIRSLSyFDTPDYKKLHSLLE 263
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
240-436 3.88e-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: 66.97  E-value: 3.88e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVW---------MGYYKNNMKVAIKTLKEGTMSpeafLGEANVMKALQHERLVRL-YAVVTKEPIY 309
Cdd:cd05630   1 TFRQYRVLGKGGFGEVCacqvratgkMYACKKLEKKRIKKRKGEAMA----LNEKQILEKVNSRFVVSLaYAYETKDALC 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 310 IVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEY 389
Cdd:cd05630  77 LVLTLMNGGDLKFHIYHMGQAGFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAVHVPEGQ 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 33469982 390 TAQeGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05630 157 TIK-GRVGTVGYMAPEVVKNERYTFSPDWWALGCLLYEMIA-GQSPF 201
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
283-482 5.62e-12

Catalytic domain of Numb-Associated Kinase (NAK)-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 Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It 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. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-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: 270939 [Multi-domain]  Cd Length: 277  Bit Score: 66.15  E-value: 5.62e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 283 GEANVMKALQ-HERLVRL---YAVVTKEPIY---IVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMN 355
Cdd:cd14037  49 REIEIMKRLSgHKNIVGYidsSANRSGNGVYevlLLMEYCKGGGVIDLMNQRLQTGLTESEILKIFCDVCEAVAAMHYLK 128
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 356 S--IHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKF---PIK------WTAPEAIHF---GVFTIKADVWSF 421
Cdd:cd14037 129 PplIHRDLKVENVLISDSGNYKLCDFGSATTKILPPQTKQGVTYveeDIKkyttlqYRAPEMIDLyrgKPITEKSDIWAL 208
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 422 GVLLMEVVTYgRVPYpGMSNPEVIRNLErgYRMPRPDTCPPELyRGVIAECWRSRPEERPT 482
Cdd:cd14037 209 GCLLYKLCFY-TTPF-EESGQLAILNGN--FTFPDNSRYSKRL-HKLIRYMLEEDPEKRPN 264
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
244-484 6.97e-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: 65.49  E-value: 6.97e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMK-VAIKTLK-----EGTMSPEAFLG----EANVMKALQ---HERLVRLYAVV-TKEPIY 309
Cdd:cd14004   5 LKEMGEGAYGQVNLAIYKSKGKeVVIKFIFkerilVDTWVRDRKLGtvplEIHILDTLNkrsHPNIVKLLDFFeDDEFYY 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 310 IVTEYMARGC-LLDFLKTDEGSRLSLPRLIdmSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSe 388
Cdd:cd14004  85 LVMEKHGSGMdLFDFIERKPNMDEKEAKYI--FRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAAYIKS- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 ytaqegAKF-----PIKWTAPEAIHFGVFTIKA-DVWSFGVLLMEVVtYGRVPYpgmsnPEVIRNLERGYRMPRPDTcpP 462
Cdd:cd14004 162 ------GPFdtfvgTIDYAAPEVLRGNPYGGKEqDIWALGVLLYTLV-FKENPF-----YNIEEILEADLRIPYAVS--E 227
                       250       260
                ....*....|....*....|..
gi 33469982 463 ELYRgVIAECWRSRPEERPTFE 484
Cdd:cd14004 228 DLID-LISRMLNRDVGDRPTIE 248
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
241-480 7.29e-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: 66.23  E-value: 7.29e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLY-----AVVTKEPIYIV 311
Cdd:cd14030  27 LKFDIEIGRGSFKTVYKGLdTETTVEVAWCELQDRKLSKserQRFKEEAGMLKGLQHPNIVRFYdswesTVKGKKCIVLV 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSRLSLPRliDMSAQIAEGMAYIERMNS--IHRDLRAANILVSEAL-CCKIADFGLARIIDSE 388
Cdd:cd14030 107 TELMTSGTLKTYLKRFKVMKIKVLR--SWCRQILKGLQFLHTRTPpiIHRDLKCDNIFITGPTgSVKIGDLGLATLKRAS 184
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YtAQEGAKFPiKWTAPEaIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNP-EVIRNLERGYRMPRPDTCPPELYRG 467
Cdd:cd14030 185 F-AKSVIGTP-EFMAPE-MYEEKYDESVDVYAFGMCMLEMAT-SEYPYSECQNAaQIYRRVTSGVKPASFDKVAIPEVKE 260
                       250
                ....*....|...
gi 33469982 468 VIAECWRSRPEER 480
Cdd:cd14030 261 IIEGCIRQNKDER 273
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
241-480 7.34e-12

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: 65.90  E-value: 7.34e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNN-MKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLY-----AVVTKEPIYIV 311
Cdd:cd14031  12 LKFDIELGRGAFKTVYKGLDTETwVEVAWCELQDRKLTKaeqQRFKEEAEMLKGLQHPNIVRFYdswesVLKGKKCIVLV 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTdegSRLSLPRLI-DMSAQIAEGMAYIERMNS--IHRDLRAANILVSEAL-CCKIADFGLARIIDS 387
Cdd:cd14031  92 TELMTSGTLKTYLKR---FKVMKPKVLrSWCRQILKGLQFLHTRTPpiIHRDLKCDNIFITGPTgSVKIGDLGLATLMRT 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYtAQEGAKFPiKWTAPEaIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSN-PEVIRNLERGYRMPRPDTCPPELYR 466
Cdd:cd14031 169 SF-AKSVIGTP-EFMAPE-MYEEHYDESVDVYAFGMCMLEMAT-SEYPYSECQNaAQIYRKVTSGIKPASFNKVTDPEVK 244
                       250
                ....*....|....
gi 33469982 467 GVIAECWRSRPEER 480
Cdd:cd14031 245 EIIEGCIRQNKSER 258
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
235-481 7.55e-12

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: 66.61  E-value: 7.55e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 235 EIPRQSLRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLY-AVVTKEPIYI 310
Cdd:cd06649   1 ELKDDDFERISELGAGNGGVVTKVQHKPSGLIMARKLIHLEIKPairNQIIRELQVLHECNSPYIVGFYgAFYSDGEISI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYI-ERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSE 388
Cdd:cd06649  81 CMEHMDGGSLDQVLK--EAKRIPEEILGKVSIAVLRGLAYLrEKHQIMHRDVKPSNILVNSRGEIKLCDFGVSgQLIDSM 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 389 YTAQEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPgmsnPEVIRNLERGYRMPRPDTCPPELYrgv 468
Cdd:cd06649 159 ANSFVGTR---SYMSPERLQGTHYSVQSDIWSMGLSLVELAI-GRYPIP----PPDAKELEAIFGRPVVDGEEGEPH--- 227
                       250
                ....*....|...
gi 33469982 469 iAECWRSRPEERP 481
Cdd:cd06649 228 -SISPRPRPPGRP 239
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
245-488 8.93e-12

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270991 [Multi-domain]  Cd Length: 263  Bit Score: 65.39  E-value: 8.93e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTLKEgtmSPEAFLgEANV-MKALQHERLVRLYAVVtkEPIY-------IVTEYM 315
Cdd:cd14089   7 QVLGLGINGKVLECFHKkTGEKFALKVLRD---NPKARR-EVELhWRASGCPHIVRIIDVY--ENTYqgrkcllVVMECM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 316 ARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSE-----ALccKIADFGLARIIDSEYT 390
Cdd:cd14089  81 EGGELFSRIQERADSAFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSkgpnaIL--KLTDFGFAKETTTKKS 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 391 AQEGAKFPIkWTAPEAIHFGVFTIKADVWSFGVlLMEVVTYGRVPY---------PGMSNPevIRNLErgYRMPRPD-TC 460
Cdd:cd14089 159 LQTPCYTPY-YVAPEVLGPEKYDKSCDMWSLGV-IMYILLCGYPPFysnhglaisPGMKKR--IRNGQ--YEFPNPEwSN 232
                       250       260
                ....*....|....*....|....*....
gi 33469982 461 PPELYRGVIAECWRSRPEERPTF-EFLQS 488
Cdd:cd14089 233 VSEEAKDLIRGLLKTDPSERLTIeEVMNH 261
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
242-436 9.70e-12

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271101 [Multi-domain]  Cd Length: 286  Bit Score: 65.76  E-value: 9.70e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKNN-----MKV-------------------AIKTLKEGTMSP----EAFLGEANVMKALQH 293
Cdd:cd14199   5 KLKDEIGKGSYGVVKLAYNEDDntyyaMKVlskkklmrqagfprrppprGARAAPEGCTQPrgpiERVYQEIAILKKLDH 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 294 ERLVRLYAVV---TKEPIYIVTEYMARGCLLDF--LK--TDEGSRLSLPRLIdmsaqiaEGMAYIERMNSIHRDLRAANI 366
Cdd:cd14199  85 PNVVKLVEVLddpSEDHLYMVFELVKQGPVMEVptLKplSEDQARFYFQDLI-------KGIEYLHYQKIIHRDVKPSNL 157
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 367 LVSEALCCKIADFGLARII---DSEYTAQEGAKfpiKWTAPEAIH--FGVFTIKA-DVWSFGVLLMEVVtYGRVPY 436
Cdd:cd14199 158 LVGEDGHIKIADFGVSNEFegsDALLTNTVGTP---AFMAPETLSetRKIFSGKAlDVWAMGVTLYCFV-FGQCPF 229
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
244-428 1.20e-11

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: 65.37  E-value: 1.20e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMS---PEAFLGEANVMKALQ---HERLVRLYAVVT------KEPIYI 310
Cdd:cd07863   5 VAEIGVGAYGTVYKARDPHSGHfVALKSVRVQTNEdglPLSTVREVALLKRLEafdHPNIVRLMDVCAtsrtdrETKVTL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGcLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIidseYT 390
Cdd:cd07863  85 VFEHVDQD-LRTYLDKVPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLARI----YS 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 33469982 391 AQEgAKFPIKWT----APEAIHFGVFTIKADVWSFGVLLMEV 428
Cdd:cd07863 160 CQM-ALTPVVVTlwyrAPEVLLQSTYATPVDMWSVGCIFAEM 200
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
117-219 1.37e-11

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: 61.00  E-value: 1.37e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 117 ESLEMERWFFRSQGRKEAErQLLAPINKAGSFLIRESeTNKGAFSLSV--KDVTTQGELIKHYKIRCLDEGGYYISPRIT 194
Cdd:cd10397   1 DSLEMYEWYSKNMTRSQAE-QLLKQEGKEGGFIVRDS-SKAGKYTVSVfaKSAGDPQGVIRHYVVCSTPQSQYYLAEKHL 78
                        90       100
                ....*....|....*....|....*
gi 33469982 195 FPSLQALVQHYSKKGDGLCQRLTLP 219
Cdd:cd10397  79 FSTIPELINYHQHNAAGLISRLKYP 103
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
343-493 1.43e-11

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 66.58  E-value: 1.43e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  343 QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKF---PIkWTAPEAIHFGVFTIKADVW 419
Cdd:PTZ00267 177 QIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQYSDSVSLDVASSFcgtPY-YLAPELWERKRYSKKADMW 255
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  420 SFGVLLMEVVTYGRvPYPGMSNPEVIRNLERGYRMPRPdtCP-PELYRGVIAECWRSRPEERPT------FEFLQSVLED 492
Cdd:PTZ00267 256 SLGVILYELLTLHR-PFKGPSQREIMQQVLYGKYDPFP--CPvSSGMKALLDPLLSKNPALRPTtqqllhTEFLKYVANL 332

                 .
gi 33469982  493 F 493
Cdd:PTZ00267 333 F 333
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
124-205 1.46e-11

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal 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: 198217  Cd Length: 77  Bit Score: 60.13  E-value: 1.46e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 124 WFFRSQGRKEAERQLLApINKAGSFLIRESETNKGAFSLSVKdvttQGELIKHYKIrCLDEGGYYISPRITFPSLQALVQ 203
Cdd:cd10354   2 WFHGKISREEAYNMLVK-VGGPGSFLVRESDNTPGDYSLSFR----VNEGIKHFKI-IPTGNNQFMMGGRYFSSLDDVID 75

                ..
gi 33469982 204 HY 205
Cdd:cd10354  76 RY 77
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
343-435 1.61e-11

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 65.50  E-value: 1.61e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 343 QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID----------SEYTAQegakfpiKW-TAPE-AIHFG 410
Cdd:cd07857 113 QILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARGFSenpgenagfmTEYVAT-------RWyRAPEiMLSFQ 185
                        90       100
                ....*....|....*....|....*
gi 33469982 411 VFTIKADVWSFGVLLMEVvtYGRVP 435
Cdd:cd07857 186 SYTKAIDVWSVGCILAEL--LGRKP 208
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
243-447 1.64e-11

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: 64.41  E-value: 1.64e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEV-WMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCL 320
Cdd:cd14662   4 LVKDIGSGNFGVArLMRNKETKELVAVKYIERGLKIDENVQREIINHRSLRHPNIIRFKEVVlTPTHLAIVMEYAAGGEL 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 ldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILV--SEALCCKIADFGLAR--IIDSEYTAQEGAK 396
Cdd:cd14662  84 --FERICNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLdgSPAPRLKICDFGYSKssVLHSQPKSTVGTP 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982 397 FPIkwtAPEAIHFGVFTIK-ADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRN 447
Cdd:cd14662 162 AYI---APEVLSRKEYDGKvADVWSCGVTLY-VMLVGAYPFEDPDDPKNFRK 209
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
242-436 1.74e-11

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270756 [Multi-domain]  Cd Length: 285  Bit Score: 64.68  E-value: 1.74e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVW---------MGYYKNNMKVAIKTLKEGTMSpeafLGEANVMKALQHERLVRL-YAVVTKEPIYIV 311
Cdd:cd05605   3 RQYRVLGKGGFGEVCacqvratgkMYACKKLEKKRIKKRKGEAMA----LNEKQILEKVNSRFVVSLaYAYETKDALCLV 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTA 391
Cdd:cd05605  79 LTIMNGGDLKFHIYNMGNPGFEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILLDDHGHVRISDLGLAVEIPEGETI 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 33469982 392 QeGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05605 159 R-GRVGTVGYMAPEVVKNERYTFSPDWWGLGCLIYEMIE-GQAPF 201
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
246-441 1.84e-11

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: 64.70  E-value: 1.84e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLYAVVT-KEPIYIVTEYMARGCL 320
Cdd:cd07847   8 KIGEGSYGVVFKCRNRETGQiVAIKKFVESEDDPvikKIALREIRMLKQLKHPNLVNLIEVFRrKRKLHLVFEYCDHTVL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTDEGsrlsLPRLIDMSA--QIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARII---DSEYTAQEGA 395
Cdd:cd07847  88 NELEKNPRG----VPEHLIKKIiwQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILtgpGDDYTDYVAT 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 396 KFpikWTAPEAI----HFGVftiKADVWSFGVLLMEVVTyGRVPYPGMSN 441
Cdd:cd07847 164 RW---YRAPELLvgdtQYGP---PVDVWAIGCVFAELLT-GQPLWPGKSD 206
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
247-488 1.90e-11

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: 64.22  E-value: 1.90e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGY-YKNNMKVAIK-----------TLKEGTMSPEAFL-------GEANVMKALQHERLVRLYAVVTKEP 307
Cdd:cd14100   8 LGSGGFGSVYSGIrVADGAPVAIKhvekdrvsewgELPNGTRVPMEIVllkkvgsGFRGVIRLLDWFERPDSFVLVLERP 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTeymargcLLDFLkTDEGSrlsLPRLIDMS--AQIAEGMAYIERMNSIHRDLRAANILVSEALC-CKIADFGLARI 384
Cdd:cd14100  88 EPVQD-------LFDFI-TERGA---LPEELARSffRQVLEAVRHCHNCGVLHRDIKDENILIDLNTGeLKLIDFGSGAL 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 385 I-DSEYTAQEGAKFpikWTAPEAIHFGVFTIK-ADVWSFGVLLMEVVTyGRVPYPgmSNPEVIRNlERGYRMPRPDTCpp 462
Cdd:cd14100 157 LkDTVYTDFDGTRV---YSPPEWIRFHRYHGRsAAVWSLGILLYDMVC-GDIPFE--HDEEIIRG-QVFFRQRVSSEC-- 227
                       250       260
                ....*....|....*....|....*.
gi 33469982 463 elyRGVIAECWRSRPEERPTFEFLQS 488
Cdd:cd14100 228 ---QHLIKWCLALRPSDRPSFEDIQN 250
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
240-436 1.99e-11

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


Pssm-ID: 173720 [Multi-domain]  Cd Length: 285  Bit Score: 64.63  E-value: 1.99e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVW---------MGYYKNNMKVAIKTLKEGTMSpeafLGEANVMKALQHERLVRL-YAVVTKEPIY 309
Cdd:cd05631   1 TFRHYRVLGKGGFGEVCacqvratgkMYACKKLEKKRIKKRKGEAMA----LNEKRILEKVNSRFVVSLaYAYETKDALC 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 310 IVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEY 389
Cdd:cd05631  77 LVLTIMNGGDLKFHIYNMGNPGFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAVQIPEGE 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 33469982 390 TAQeGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05631 157 TVR-GRVGTVGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQ-GQSPF 201
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
238-438 2.14e-11

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: 64.99  E-value: 2.14e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 238 RQSLRLVRKLGSGQFGEVW---------MGYYKNNMKVAIKTLKEGTMSpeafLGEANVMKALQHERLVRL-YAVVTKEP 307
Cdd:cd05632   1 KNTFRQYRVLGKGGFGEVCacqvratgkMYACKRLEKKRIKKRKGESMA----LNEKQILEKVNSQFVVNLaYAYETKDA 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIdS 387
Cdd:cd05632  77 LCLVLTIMNGGDLKFHIYNMGNPGFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKI-P 155
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 33469982 388 EYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd05632 156 EGESIRGRVGTVGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIE-GQSPFRG 205
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
242-484 2.19e-11

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: 64.18  E-value: 2.19e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEVWMGYYKN-NMKVAIKtlkegtmspeaFLGEANVMKALQHERLVRlyavVTKEpIYIVTEYMARGC- 319
Cdd:cd14005   3 EVGDLLGKGGFGTVYSGVRIRdGLPVAVK-----------FVPKSRVTEWAMINGPVP----VPLE-IALLLKASKPGVp 66
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 ----LLDFLKTDEGSRLSLPR------LIDM---SAQIAEGMAYI------------ERMNSIHRDLRAANILVS-EALC 373
Cdd:cd14005  67 gvirLLDWYERPDGFLLIMERpepcqdLFDFiteRGALSENLARIifrqvveavrhcHQRGVLHRDIKDENLLINlRTGE 146
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 374 CKIADFGLARII-DSEYTAQEGAKFpikWTAPEAIHFGVFTIK-ADVWSFGVLLMEVVTyGRVPYpgMSNPEVIRNLERG 451
Cdd:cd14005 147 VKLIDFGCGALLkDSVYTDFDGTRV---YSPPEWIRHGRYHGRpATVWSLGILLYDMLC-GDIPF--ENDEQILRGNVLF 220
                       250       260       270
                ....*....|....*....|....*....|...
gi 33469982 452 YRMPRPDTCppelyrGVIAECWRSRPEERPTFE 484
Cdd:cd14005 221 RPRLSKECC------DLISRCLQFDPSKRPSLE 247
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
63-113 2.61e-11

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. 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: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 58.68  E-value: 2.61e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982  63 VVALYDYTAMNDRDLQMLKGEKLQVL-KGTGDWWLArSLVTGREGYVPSNFV 113
Cdd:cd11812   2 VVALYDYTANRSDELTIHRGDIIRVLyKDNDNWWFG-SLVNGQQGYFPANYV 52
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
247-454 3.22e-11

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: 64.43  E-value: 3.22e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-VAIKTLKE-GTMSP-EAFLGEANVMKALQHERLVRLYAV----VTKEPIyIVTEYMARGC 319
Cdd:cd13988   1 LGQGATANVFRGRHKKTGDlYAVKVFNNlSFMRPlDVQMREFEVLKKLNHKNIVKLFAIeeelTTRHKV-LVMELCPCGS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEGSR-LSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANIL--VSEALCC--KIADFGLAR-IIDSE----- 388
Cdd:cd13988  80 LYTVLEEPSNAYgLPESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMrvIGEDGQSvyKLTDFGAAReLEDDEqfvsl 159
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33469982 389 YTAQEgakfpikWTAPEAIHFGV--------FTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEviRNLERGYRM 454
Cdd:cd13988 160 YGTEE-------YLHPDMYERAVlrkdhqkkYGATVDLWSIGVTFYHAAT-GSLPFRPFEGPR--RNKEVMYKI 223
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
244-438 3.33e-11

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270752 [Multi-domain]  Cd Length: 328  Bit Score: 64.64  E-value: 3.33e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKL-GSGQFGEVWMGYYKNNMKV-AIKTLKEG-TMSPEA---FLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMA 316
Cdd:cd05601   5 VKNViGRGHFGEVQVVKEKATGDIyAMKVLKKSeTLAQEEvsfFEEERDIMAKANSPWITKLqYAFQDSENLYLVMEYHP 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKTDEGsrlSLPRliDMS----AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ 392
Cdd:cd05601  85 GGDLLSLLSRYDD---IFEE--SMArfylAELVLAIHSLHSMGYVHRDIKPENILIDRTGHIKLADFGSAAKLSSDKTVT 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 393 egAKFPI---KWTAPEAIHF------GVFTIKADVWSFGVLLMEVVtYGRVPYPG 438
Cdd:cd05601 160 --SKMPVgtpDYIAPEVLTSmnggskGTYGVECDWWSLGIVAYEML-YGKTPFTE 211
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
279-425 3.94e-11

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: 63.53  E-value: 3.94e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 279 EAFLGEANVMKALQ-HERLVRLYAVV-TKEPIYIVTEYMARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNS 356
Cdd:cd14093  53 EATRREIEILRQVSgHPNIIELHDVFeSPTFIFLVFELCRKGELFDYLT--EVVTLSEKKTRRIMRQLFEAVEFLHSLNI 130
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469982 357 IHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPiKWTAPEAIHFGVF------TIKADVWSFGVLL 425
Cdd:cd14093 131 VHRDLKPENILLDDNLNVKISDFGFATRLDEGEKLRELCGTP-GYLAPEVLKCSMYdnapgyGKEVDMWACGVIM 204
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
247-483 4.63e-11

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: 63.38  E-value: 4.63e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMG---------YYKNNMKVAIKTLKEGTMSpEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMAR 317
Cdd:cd14208   7 LGKGSFTKIYRGlrtdeeddeRCETEVLLKVMDPTHGNCQ-ESFLEAASIMSQISHKHLVLLHGVCVGKDSIMVQEFVCH 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLKTD-EGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSE------ALCCKIADFGLA-RIIDSEY 389
Cdd:cd14208  86 GALDLYLKKQqQKGPVAISWKLQVVKQLAYALNYLEDKQLVHGNVSAKKVLLSRegdkgsPPFIKLSDPGVSiKVLDEEL 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 390 TAQEgakfpIKWTAPEAIH-FGVFTIKADVWSFGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCppELyRGV 468
Cdd:cd14208 166 LAER-----IPWVAPECLSdPQNLALEADKWGFGATLWEIFSGGHMPLSALDPSKKLQFYNDRKQLPAPHWI--EL-ASL 237
                       250
                ....*....|....*
gi 33469982 469 IAECWRSRPEERPTF 483
Cdd:cd14208 238 IQQCMSYNPLLRPSF 252
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
247-491 4.81e-11

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: 63.49  E-value: 4.81e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNnmKVAIKTL---KEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd14153   8 IGKGRFGQVYHGRWHG--EVAIRLIdieRDNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCkIADFGLARI--IDSEYTAQEGAKFPIKW 401
Cdd:cd14153  86 VVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGLFTIsgVLQAGRREDKLRIQSGW 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 402 ---TAPEAIHFGV---------FTIKADVWSFGVLLMEVvtYGRV-PYPGMSNPEVIRNLERGYRMPRPDTCPPELYRGV 468
Cdd:cd14153 165 lchLAPEIIRQLSpeteedklpFSKHSDVFAFGTIWYEL--HAREwPFKTQPAEAIIWQVGSGMKPNLSQIGMGKEISDI 242
                       250       260
                ....*....|....*....|...
gi 33469982 469 IAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14153 243 LLFCWAYEQEERPTFSKLMEMLE 265
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
261-492 5.21e-11

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 63.57  E-value: 5.21e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 261 KNNMKVAIKTLKEgtmspeaflgEANVMKALQHERLV--RLYAVVTKEPIYIVTEY--MARGCLLDFLKTDEGSRLSLPR 336
Cdd:cd14001  42 KGQRSLYQERLKE----------EAKILKSLNHPNIVgfRAFTKSEDGSLCLAMEYggKSLNDLIEERYEAGLGPFPAAT 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 337 LIDMSAQIAEGMAYIERMNSI-HRDLRAANILVS---EAlcCKIADFGLARIIDSEYTAQEGAKFPI----KWTAPEAIH 408
Cdd:cd14001 112 ILKVALSIARALEYLHNEKKIlHGDIKSGNVLIKgdfES--VKLCDFGVSLPLTENLEVDSDPKAQYvgtePWKAKEALE 189
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 409 FG-VFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPE--------------VIRNLE-RGYRMPRPDTCPPELYRGVI--- 469
Cdd:cd14001 190 EGgVITDKADIFAYGLVLWEMMTL-SVPHLNLLDIEdddedesfdedeedEEAYYGtLGTRPALNLGELDDSYQKVIelf 268
                       250       260
                ....*....|....*....|...
gi 33469982 470 AECWRSRPEERPTFEFLQSVLED 492
Cdd:cd14001 269 YACTQEDPKDRPSAAHIVEALEA 291
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
247-436 5.27e-11

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 63.88  E-value: 5.27e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTL-KEGTMSP-EA--FLGEANV-MKALQHERLVRL-YAVVTKEPIYIVTEYMARGC 319
Cdd:cd05575   3 IGKGSFGKVLLARHKAEGKLyAVKVLqKKAILKRnEVkhIMAERNVlLKNVKHPFLVGLhYSFQTKDKLYFVLDYVNGGE 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 320 LLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR--IIDSEYTaqegAKF 397
Cdd:cd05575  83 LFFHLQRER--HFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCKegIEPSDTT----STF 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 33469982 398 ---PiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVtYGRVPY 436
Cdd:cd05575 157 cgtP-EYLAPEVLRKQPYDRTVDWWCLGAVLYEML-YGLPPF 196
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
63-114 5.52e-11

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: 57.67  E-value: 5.52e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 33469982  63 VVALYDYTAMNDRDLQMLKGEKLQVLKGTG-DWWLARSlVTGREGYVPSNFVA 114
Cdd:cd11768   2 VVALYDFQPIEPGDLPLEKGEEYVVLDDSNeHWWRARD-KNGNEGYIPSNYVT 53
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
292-450 5.95e-11

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: 63.42  E-value: 5.95e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 292 QHERLVRLYAVVT-KEPIYIVTEYMARGCLLDFLktdegsrLSLPRLIDMSAQ-----IAEGMAYIERMNSIHRDLRAAN 365
Cdd:cd14091  52 QHPNIITLRDVYDdGNSVYLVTELLRGGELLDRI-------LRQKFFSEREASavmktLTKTVEYLHSQGVVHRDLKPSN 124
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 366 ILVSEALC----CKIADFGLARIIDSE--------YTAQegakfpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGR 433
Cdd:cd14091 125 ILYADESGdpesLRICDFGFAKQLRAEngllmtpcYTAN--------FVAPEVLKKQGYDAACDIWSLGVLLYTMLA-GY 195
                       170
                ....*....|....*....
gi 33469982 434 VPYPGMSN--PEVIrnLER 450
Cdd:cd14091 196 TPFASGPNdtPEVI--LAR 212
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
243-384 6.86e-11

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: 63.74  E-value: 6.86e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSpeaflgEANVMKALQHER----------LVRL-YAVVTKEPIYI 310
Cdd:cd05610   8 IVKPISRGAFGKVYLGRKKNNSKLyAVKVVKKADMI------NKNMVHQVQAERdalalskspfIVHLyYSLQSANNVYL 81
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33469982 311 VTEYMARGCLLDFLKT----DEgsrlslPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI 384
Cdd:cd05610  82 VMEYLIGGDVKSLLHIygyfDE------EMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKV 153
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
247-482 7.11e-11

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: 62.67  E-value: 7.11e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-VAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLYAVVTKEPIYI-VTEYMARGCLLDFL 324
Cdd:cd14115   1 IGRGRFSIVKKCLHKATRKdVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYIlVLELMDDGRLLDYL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 325 KT-DEgsrLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEAL---CCKIADFGLARIIDSEYTAQEGAKFPiK 400
Cdd:cd14115  81 MNhDE---LMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIDLRIpvpRVKLIDLEDAVQISGHRHVHHLLGNP-E 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 401 WTAPEAIHFGVFTIKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNLergyrmPRPDTC-PPELYRGV-------IAEC 472
Cdd:cd14115 157 FAAPEVIQGTPVSLATDIWSIGVLTY-VMLSGVSPFLDESKEETCINV------CRVDFSfPDEYFGDVsqaardfINVI 229
                       250
                ....*....|
gi 33469982 473 WRSRPEERPT 482
Cdd:cd14115 230 LQEDPRRRPT 239
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
247-438 7.91e-11

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: 63.18  E-value: 7.91e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM----SPEAFLGEANVMkALQHER--LVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd05587   4 LGKGSFGKVMLAERKGTDELyAIKILKKDVIiqddDVECTMVEKRVL-ALSGKPpfLTQLHSCFqTMDRLYFVMEYVNGG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLdFLKTDEGsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARI-IDSEYTAQEGAKF 397
Cdd:cd05587  83 DLM-YHIQQVG-KFKEPVAVFYAAEIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKEgIFGGKTTRTFCGT 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 33469982 398 PiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd05587 161 P-DYIAPEIIAYQPYGKSVDWWAYGVLLYEMLA-GQPPFDG 199
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
352-442 7.99e-11

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: 62.77  E-value: 7.99e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 352 ERMNSIHRDLRAANILVSEALCCKIADFGLA-RIIDSEYTAQEGAKFPikWTAPEAI----HFGVFTIKADVWSFGVLLM 426
Cdd:cd06616 127 EELKIIHRDVKPSNILLDRNGNIKLCDFGISgQLVDSIAKTRDAGCRP--YMAPERIdpsaSRDGYDVRSDVWSLGITLY 204
                        90
                ....*....|....*.
gi 33469982 427 EVVTyGRVPYPGMSNP 442
Cdd:cd06616 205 EVAT-GKFPYPKWNSV 219
STKc_PIM2 cd14101
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
247-484 8.02e-11

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: 62.56  E-value: 8.02e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPEAFLgeANVMKALQHERLVRLYAVVTKEPIYIVteymargcLLDFLK 325
Cdd:cd14101   8 LGKGGFGTVYAGHrISDGLQVAIKQISRNRVQQWSKL--PGVNPVPNEVALLQSVGGGPGHRGVIR--------LLDWFE 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 326 TDEGSRLSLPR------LIDMSA---------------QIAEGMAYIERMNSIHRDLRAANILVS-EALCCKIADFGL-A 382
Cdd:cd14101  78 IPEGFLLVLERpqhcqdLFDYITergaldeslarrffkQVVEAVQHCHSKGVVHRDIKDENILVDlRTGDIKLIDFGSgA 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 383 RIIDSEYTAQEGAKF--PIKWTAPEAIHfgvfTIKADVWSFGVLLMEVVTyGRVPYpgmSNPEVIRNLERGYRMPRPDTC 460
Cdd:cd14101 158 TLKDSMYTDFDGTRVysPPEWILYHQYH----ALPATVWSLGILLYDMVC-GDIPF---ERDTDILKAKPSFNKRVSNDC 229
                       250       260
                ....*....|....*....|....
gi 33469982 461 ppelyRGVIAECWRSRPEERPTFE 484
Cdd:cd14101 230 -----RSLIRSCLAYNPSDRPSLE 248
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
241-480 8.71e-11

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: 62.40  E-value: 8.71e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNN-MKVAIKTLKEGTMSP---EAFLGEANVMKALQHERLVRLY-----AVVTKEPIYIV 311
Cdd:cd14032   3 LKFDIELGRGSFKTVYKGLDTETwVEVAWCELQDRKLTKverQRFKEEAEMLKGLQHPNIVRFYdfwesCAKGKRCIVLV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTdegSRLSLPRLI-DMSAQIAEGMAYIERMNS--IHRDLRAANILVSEAL-CCKIADFGLARIIDS 387
Cdd:cd14032  83 TELMTSGTLKTYLKR---FKVMKPKVLrSWCRQILKGLLFLHTRTPpiIHRDLKCDNIFITGPTgSVKIGDLGLATLKRA 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYtAQEGAKFPiKWTAPEaIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSN-PEVIRNLERGYRMPRPDTCPPELYR 466
Cdd:cd14032 160 SF-AKSVIGTP-EFMAPE-MYEEHYDESVDVYAFGMCMLEMAT-SEYPYSECQNaAQIYRKVTCGIKPASFEKVTDPEIK 235
                       250
                ....*....|....
gi 33469982 467 GVIAECWRSRPEER 480
Cdd:cd14032 236 EIIGECICKNKEER 249
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
247-436 9.50e-11

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 62.89  E-value: 9.50e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMKV-AIKTLK----------EGTMSPEAFLGEANvmkalQHERLVRLYAVV-TKEPIYIVTEY 314
Cdd:cd05591   3 LGKGSFGKVMLAERKGTDEVyAIKVLKkdvilqdddvDCTMTEKRILALAA-----KHPFLTALHSCFqTKDRLFFVMEY 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLdfLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR--IIDSEYTaQ 392
Cdd:cd05591  78 VNGGDLM--FQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKegILNGKTT-T 154
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 33469982 393 EGAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05591 155 TFCGTP-DYIAPEILQELEYGPSVDWWALGVLMYEMMA-GQPPF 196
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
241-481 9.58e-11

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: 62.53  E-value: 9.58e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSP-EAFLGEANVMKALQ-HERLVRLYAVVT---KEPIYIVTEY 314
Cdd:cd14036   2 LRIKRVIAEGGFAFVYEAQdVGTGKEYALKRLLSNEEEKnKAIIQEINFMKKLSgHPNIVQFCSAASigkEESDQGQAEY 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 M-----ARGCLLDFLKTDEG-SRLSLPRLIDMSAQIAEGMAYIERMNS--IHRDLRAANILVSEALCCKIADFGLARII- 385
Cdd:cd14036  82 LlltelCKGQLVDFVKKVEApGPFSPDTVLKIFYQTCRAVQHMHKQSPpiIHRDLKIENLLIGNQGQIKLCDFGSATTEa 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 386 ---DSEYTAQEGAKF---------PIkWTAPEAIH-FGVFTI--KADVWSFGVLLMeVVTYGRVPYpgmSNPEVIRNLER 450
Cdd:cd14036 162 hypDYSWSAQKRSLVedeitrnttPM-YRTPEMIDlYSNYPIgeKQDIWALGCILY-LLCFRKHPF---EDGAKLRIINA 236
                       250       260       270
                ....*....|....*....|....*....|.
gi 33469982 451 GYRMPRPDTcPPELYRGVIAECWRSRPEERP 481
Cdd:cd14036 237 KYTIPPNDT-QYTVFHDLIRSTLKVNPEERL 266
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
122-220 9.77e-11

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198221  Cd Length: 100  Bit Score: 58.61  E-value: 9.77e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 122 ERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDvttqGELIKHYKIRCLDEGGYYISPRITFPSLQAL 201
Cdd:cd10358   2 EPWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRD----TQAVRHYKIWRRAGGRLHLNEAVSFLSLPEL 77
                        90
                ....*....|....*....
gi 33469982 202 VQHYSKKGDGLCQRLTLPC 220
Cdd:cd10358  78 VNYHRAQSLSHGLRLAAPC 96
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
247-491 1.05e-10

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: 62.19  E-value: 1.05e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGY-YKNNMKVAIKTLKEGTMSPEAFL----GEANVMKALQHERLVRLYAVVTKEP-IYIVTEYMARGCL 320
Cdd:cd14186   9 LGKGSFACVYRARsLHTGLEVAIKMIDKKAMQKAGMVqrvrNEVEIHCQLKHPSILELYNYFEDSNyVYLVLEMCHNGEM 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLK------TDEGSRLSLprlidmsAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA---RIIDSEYTA 391
Cdd:cd14186  89 SRYLKnrkkpfTEDEARHFM-------HQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLAtqlKMPHEKHFT 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 392 QEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYpgmSNPEVIRNLER----GYRMprPDTCPPELyRG 467
Cdd:cd14186 162 MCGTP---NYISPEIATRSAHGLESDVWSLGCMFYTLLV-GRPPF---DTDTVKNTLNKvvlaDYEM--PAFLSREA-QD 231
                       250       260
                ....*....|....*....|....
gi 33469982 468 VIAECWRSRPEERPTfefLQSVLE 491
Cdd:cd14186 232 LIHQLLRKNPADRLS---LSSVLD 252
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
225-436 1.06e-10

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: 62.15  E-value: 1.06e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 225 PQNPWAQDEwEIPRQSLRLVRKLGSGQFGEVWMGyyknnmkvAIKTLKEGTMspEAFLGEANVMKALQHERLVRLY-AVV 303
Cdd:cd14111   1 PQKPYTFLD-EKARGRFGVIRRCRENATGKNFPA--------KIVPYQAEEK--QGVLQEYEILKSLHHERIMALHeAYI 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 TKEPIYIVTEYMARGCLLDFLKtdEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR 383
Cdd:cd14111  70 TPRYLVLIAEFCSGKELLHSLI--DRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQ 147
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 33469982 384 IIDSEYTAQEGAKF-PIKWTAPEAIHFGVFTIKADVWSFGVLLMeVVTYGRVPY 436
Cdd:cd14111 148 SFNPLSLRQLGRRTgTLEYMAPEMVKGEPVGPPADIWSIGVLTY-IMLSGRSPF 200
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
283-436 1.11e-10

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: 62.38  E-value: 1.11e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 283 GEANVMKALQHERLVRLYAVV---TKEPIYIVTEYMargclldflktDEGSRLSLPRLIDMSAQIAE--------GMAYI 351
Cdd:cd14118  63 REIAILKKLDHPNVVKLVEVLddpNEDNLYMVFELV-----------DKGAVMEVPTDNPLSEETARsyfrdivlGIEYL 131
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 352 ERMNSIHRDLRAANILVSEALCCKIADFGLARI---IDSEYTAQEGAKfpiKWTAPEAIHFG--VFTIKA-DVWSFGVLL 425
Cdd:cd14118 132 HYQKIIHRDIKPSNLLLGDDGHVKIADFGVSNEfegDDALLSSTAGTP---AFMAPEALSESrkKFSGKAlDIWAMGVTL 208
                       170
                ....*....|.
gi 33469982 426 MEVVtYGRVPY 436
Cdd:cd14118 209 YCFV-FGRCPF 218
PHA02988 PHA02988
hypothetical protein; Provisional
262-482 1.16e-10

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 62.45  E-value: 1.16e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  262 NNMKVAIKTLKEGTMSPEAFL----GEANVMKALQHERLVRLYA----VVTKEP-IYIVTEYMARGCLLDFLktDEGSRL 332
Cdd:PHA02988  42 NNKEVIIRTFKKFHKGHKVLIditeNEIKNLRRIDSNNILKIYGfiidIVDDLPrLSLILEYCTRGYLREVL--DKEKDL 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  333 SLPRLIDMSAQIAEGMAYIER-MNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAkfpIKWTAPEAIH--F 409
Cdd:PHA02988 120 SFKTKLDMAIDCCKGLYNLYKyTNKPYKNLTSVSFLVTENYKLKIICHGLEKILSSPPFKNVNF---MVYFSYKMLNdiF 196
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33469982  410 GVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNL-ERGYRMPRPDTCPPELyRGVIAECWRSRPEERPT 482
Cdd:PHA02988 197 SEYTIKDDIYSLGVVLWEIFT-GKIPFENLTTKEIYDLIiNKNNSLKLPLDCPLEI-KCIVEACTSHDSIKRPN 268
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
284-424 1.32e-10

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: 61.97  E-value: 1.32e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 284 EANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCLLDFLKTDegSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLR 362
Cdd:cd14184  49 EVSILRRVKHPNIIMLIEEMdTPAELYLVMELVKGGDLFDAITSS--TKYTERDASAMVYNLASALKYLHGLCIVHRDIK 126
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 363 AANILVSE----ALCCKIADFGLARIIDSEYTAQEGAKfpiKWTAPEAIHFGVFTIKADVWSFGVL 424
Cdd:cd14184 127 PENLLVCEypdgTKSLKLGDFGLATVVEGPLYTVCGTP---TYVAPEIIAETGYGLKVDIWAAGVI 189
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
247-451 1.44e-10

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: 62.35  E-value: 1.44e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEAflgEANVMKAL-QHERLVRLYAVVTK-EPIYIVTEYMARGCLLD- 322
Cdd:cd14175   9 IGVGSYSVCKRCVHKaTNMEYAVKVIDKSKRDPSE---EIEILLRYgQHPNIITLKDVYDDgKHVYLVTELMRGGELLDk 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 -----FLKTDEGSRLSLprlidmsaQIAEGMAYIERMNSIHRDLRAANIL-VSEA---LCCKIADFGLARIIDSEYTAQE 393
Cdd:cd14175  86 ilrqkFFSEREASSVLH--------TICKTVEYLHSQGVVHRDLKPSNILyVDESgnpESLRICDFGFAKQLRAENGLLM 157
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 394 GAKFPIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY---PGMSNPEVIRNLERG 451
Cdd:cd14175 158 TPCYTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLA-GYTPFangPSDTPEEILTRIGSG 217
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
124-212 1.52e-10

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


Pssm-ID: 198211  Cd Length: 86  Bit Score: 57.43  E-value: 1.52e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 124 WFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVkdvtTQGELIKHYKIRCLDEGGYYISPRITFPSLQALVQ 203
Cdd:cd10348   2 WLHGALDRNEAVEILKQKADADGSFLVRYSRRRPGGYVLTL----VYENHVYHFEIQNRDDKWFYIDDGPYFESLEHLIE 77

                ....*....
gi 33469982 204 HYSKKGDGL 212
Cdd:cd10348  78 HYTQFADGL 86
STKc_CdkB_plant cd07837
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; ...
246-429 1.72e-10

Catalytic domain of the Serine/Threonine Kinase, 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. 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 CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270830 [Multi-domain]  Cd Length: 294  Bit Score: 62.16  E-value: 1.72e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMK-VAIKTLK-----EGTmsPEAFLGEANVMKALQHE-RLVRLYAVVT-----KEPIYIVTE 313
Cdd:cd07837   8 KIGEGTYGKVYKARDKNTGKlVALKKTRlemeeEGV--PSTALREVSLLQMLSQSiYIVRLLDVEHveengKPLLYLVFE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARgcllDFLKTDEGSRLSLPRLIDMSA------QIAEGMAYIERMNSIHRDLRAANILVSEAL-CCKIADFGLARIID 386
Cdd:cd07837  86 YLDT----DLKKFIDSYGRGPHNPLPAKTiqsfmyQLCKGVAHCHSHGVMHRDLKPQNLLVDKQKgLLKIADLGLGRAFT 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 33469982 387 SEYTAQEGAKFPIKWTAPEAIHFGV-FTIKADVWSFGVLLMEVV 429
Cdd:cd07837 162 IPIKSYTHEIVTLWYRAPEVLLGSThYSTPVDMWSVGCIFAEMS 205
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
241-491 1.78e-10

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: 61.91  E-value: 1.78e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 241 LRLVRKLGSGQFGEVWMGYYKNnmKVAIKTLK-EGTMSPEAFLGEANVMKALQ--HERLVRLYAVVTKEP-IYIVTEYMA 316
Cdd:cd14152   2 IELGELIGQGRWGKVHRGRWHG--EVAIRLLEiDGNNQDHLKLFKKEVMNYRQtrHENVVLFMGACMHPPhLAIITSFCK 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLKtDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCkIADFGLARI--IDSEYTAQEG 394
Cdd:cd14152  80 GRTLYSFVR-DPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDFGLFGIsgVVQEGRRENE 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 395 AKFPIKWT---APEAIHFGV---------FTIKADVWSFGVLLMEVVTYGRvPYPGMSNPEVIRNLERGYRMPR--PDTC 460
Cdd:cd14152 158 LKLPHDWLcylAPEIVREMTpgkdedclpFSKAADVYAFGTIWYELQARDW-PLKNQPAEALIWQIGSGEGMKQvlTTIS 236
                       250       260       270
                ....*....|....*....|....*....|.
gi 33469982 461 PPELYRGVIAECWRSRPEERPTFEFLQSVLE 491
Cdd:cd14152 237 LGKEVTEILSACWAFDLEERPSFTLLMDMLE 267
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
124-207 1.87e-10

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. 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: 198196  Cd Length: 93  Bit Score: 57.52  E-value: 1.87e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 124 WFFRSQGRKEAERQLLAPiNKAGSFLIRESETNKGAFSLSVKDVTTQgeliKHYKIRcLDEGGYYISPRiTFPSLQALVQ 203
Cdd:cd09943   3 WYYGRITRHQAETLLNEH-GHEGDFLIRDSESNPGDYSVSLKAPGRN----KHFKVQ-VVDNVYCIGQR-KFHTMDELVE 75

                ....
gi 33469982 204 HYSK 207
Cdd:cd09943  76 HYKK 79
STKc_ROCK1 cd05622
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
243-436 2.07e-10

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270772 [Multi-domain]  Cd Length: 405  Bit Score: 62.72  E-value: 2.07e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM---SPEAFLGEA-NVMKALQHERLVRL-YAVVTKEPIYIVTEYMA 316
Cdd:cd05622  77 VVKVIGRGAFGEVQLVRHKSTRKVyAMKLLSKFEMikrSDSAFFWEErDIMAFANSPWVVQLfYAFQDDRYLYMVMEYMP 156
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 317 RGCLLDFLktdegSRLSLPRLID--MSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ-E 393
Cdd:cd05622 157 GGDLVNLM-----SNYDVPEKWArfYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEGMVRcD 231
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 33469982 394 GAKFPIKWTAPEAIHF----GVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05622 232 TAVGTPDYISPEVLKSqggdGYYGRECDWWSVGVFLYEMLV-GDTPF 277
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
122-205 2.20e-10

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


Pssm-ID: 198210  Cd Length: 81  Bit Score: 57.00  E-value: 2.20e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 122 ERWFFRSQGRKEAErQLLAPINKA-GSFLIRESETNKGAFSLSVKdvtTQGElIKHYKIRCLDEGGYYIS-PRITFPSLQ 199
Cdd:cd10347   1 LRWYHGKISREVAE-ALLLREGGRdGLFLVRESTSAPGDYVLSLL---AQGE-VLHYQIRRHGEDAFFSDdGPLIFHGLD 75

                ....*.
gi 33469982 200 ALVQHY 205
Cdd:cd10347  76 TLIEHY 81
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
242-495 2.24e-10

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: 61.35  E-value: 2.24e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 242 RLVRKLGSGQFGEV-----WMGYYKNNMKVAI----KTLKEGTMspeaflgEANVMKAL-QHERLVRLYAVV-------- 303
Cdd:cd13975   3 KLGRELGRGQYGVVyacdsWGGHFPCALKSVVppddKHWNDLAL-------EFHYTRSLpKHERIVSLHGSVidysyggg 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 TKEPIYIVTEYMARGclldfLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR 383
Cdd:cd13975  76 SSIAVLLIMERLHRD-----LYTGIKAGLSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCK 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 384 --------IIDSeytaqegakfPIKwTAPEAIHfGVFTIKADVWSFGVLLMEVVTyGRVPYPGM-----SNPEVIRNLER 450
Cdd:cd13975 151 peammsgsIVGT----------PIH-MAPELFS-GKYDNSVDVYAFGILFWYLCA-GHVKLPEAfeqcaSKDHLWNNVRK 217
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 33469982 451 GYRMPRPDTCPPELYRgVIAECWRSRPEERPTFEFLQSVLEDFYT 495
Cdd:cd13975 218 GVRPERLPVFDEECWN-LMEACWSGDPSQRPLLGIVQPKLQGIMD 261
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
240-436 2.31e-10

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


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 61.55  E-value: 2.31e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 240 SLRLVRKLGSGQFGEVWM-----GYYKNNMkVAIKTLKEGTMSPEAFLGEANVM--KALQHER----LVRL-YAVVTKEP 307
Cdd:cd05613   1 NFELLKVLGTGAYGKVFLvrkvsGHDAGKL-YAMKVLKKATIVQKAKTAEHTRTerQVLEHIRqspfLVTLhYAFQTDTK 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 308 IYIVTEYMARGCLLDFLKTDEgsRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARiids 387
Cdd:cd05613  80 LHLILDYINGGELFTHLSQRE--RFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSK---- 153
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982 388 EYTAQEGAKF-----PIKWTAPEAIHFGV--FTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05613 154 EFLLDENERAysfcgTIEYMAPEIVRGGDsgHDKAVDWWSLGVLMYELLT-GASPF 208
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
124-221 2.53e-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: 57.62  E-value: 2.53e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 124 WFFRSQGRKEAERQLLAPINKAGSFLIRESETNkGAFSLSVkdvtTQGELIKHYKIRCLDEGGYYISPRITFPSLQALVQ 203
Cdd:cd10402  12 WYHGSIARDEAERRLYSGAQPDGKFLLRERKES-GTYALSL----VYGKTVYHYRIDQDKSGKYSIPEGTKFDTLWQLVE 86
                        90
                ....*....|....*...
gi 33469982 204 HYSKKGDGLCQRLTLPCV 221
Cdd:cd10402  87 YLKLKPDGLIFVLRESCP 104
SH3_Abl cd11850
Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ...
62-115 3.18e-10

Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; 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). 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: 212784  Cd Length: 56  Bit Score: 55.50  E-value: 3.18e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVL--KGTGDWWLARSLVTGREGYVPSNFVAR 115
Cdd:cd11850   1 LFVALYDFVASGENQLSIKKGEQLRVLgyNKNGEWCEAESKSTGGQGWVPSNYITP 56
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
263-436 3.25e-10

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: 61.57  E-value: 3.25e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 263 NMKVAIKTLKEGTMSPEAflgEANVM-KALQHERLVRLYAVVTK-EPIYIVTEYMARGCLLD------FLKTDEGSRLSL 334
Cdd:cd14176  44 NMEFAVKIIDKSKRDPTE---EIEILlRYGQHPNIITLKDVYDDgKYVYVVTELMKGGELLDkilrqkFFSEREASAVLF 120
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 335 prlidmsaQIAEGMAYIERMNSIHRDLRAANIL-VSEA---LCCKIADFGLARIIDSEYTAQEGAKFPIKWTAPEAIHFG 410
Cdd:cd14176 121 --------TITKTVEYLHAQGVVHRDLKPSNILyVDESgnpESIRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLERQ 192
                       170       180
                ....*....|....*....|....*.
gi 33469982 411 VFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd14176 193 GYDAACDIWSLGVLLYTMLT-GYTPF 217
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
124-223 3.38e-10

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


Pssm-ID: 198264  Cd Length: 99  Bit Score: 56.82  E-value: 3.38e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 124 WFFRSQGRKEAERQLLAPINKAGSFLIRESETNkGAFSLSVkdvtTQGELIKHYKIRCLDEGGYYISPRITFPSLQALVQ 203
Cdd:cd10401   5 WFHGKISREESEQILLIGSKTNGKFLIRERDNN-GSYALCL----LHDGKVLHYRIDKDKTGKLSIPDGKKFDTLWQLVE 79
                        90       100
                ....*....|....*....|
gi 33469982 204 HYSKKGDGLCQRLTLPCVRP 223
Cdd:cd10401  80 HYSYKPDGLLRVLTEPCPRI 99
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
243-424 4.06e-10

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


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 60.67  E-value: 4.06e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGYYKNNMK-VAIKTL-KEGTMSPEAFL-GEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARG 318
Cdd:cd14169   7 LKEKLGEGAFSEVVLAQERGSQRlVALKCIpKKALRGKEAMVeNEIAVLRRINHENIVSLEDIYeSPTHLYLAMELVTGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 319 CLLD-FLKTDEGSRLSLPRLIdmsAQIAEGMAYIERMNSIHRDLRAANILVS---EALCCKIADFGLARIIDSEYTAQeg 394
Cdd:cd14169  87 ELFDrIIERGSYTEKDASQLI---GQVLQAVKYLHQLGIVHRDLKPENLLYAtpfEDSKIMISDFGLSKIEAQGMLST-- 161
                       170       180       190
                ....*....|....*....|....*....|
gi 33469982 395 AKFPIKWTAPEAIHFGVFTIKADVWSFGVL 424
Cdd:cd14169 162 ACGTPGYVAPELLEQKPYGKAVDVWAIGVI 191
SH3_Nck_1 cd11765
First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
62-113 4.07e-10

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: 55.12  E-value: 4.07e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSlVTGREGYVPSNFV 113
Cdd:cd11765   1 YVVAKYDYTAQGDQELSIKKNEKLTLLDDSKHWWKVQN-SSNQTGYVPSNYV 51
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
238-424 4.23e-10

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: 60.78  E-value: 4.23e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 238 RQSLRLVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPEAFL-GEANVMKALQHERLVRLYAVV-TKEPIYIVTEY 314
Cdd:cd14166   2 RETFIFMEVLGSGAFSEVYLVKQRSTGKLyALKCIKKSPLSRDSSLeNEIAVLKRIKHENIVTLEDIYeSTTHYYLVMQL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARGCLLD-FLKTDEGSRLSLPRLIDmsaQIAEGMAYIERMNSIHRDLRAANILV---SEALCCKIADFGLARIidSEYT 390
Cdd:cd14166  82 VSGGELFDrILERGVYTEKDASRVIN---QVLSAVKYLHENGIVHRDLKPENLLYltpDENSKIMITDFGLSKM--EQNG 156
                       170       180       190
                ....*....|....*....|....*....|....
gi 33469982 391 AQEGAKFPIKWTAPEAIHFGVFTIKADVWSFGVL 424
Cdd:cd14166 157 IMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVI 190
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
246-451 4.29e-10

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: 60.29  E-value: 4.29e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYK-NNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLD- 322
Cdd:cd14107   9 EIGRGTFGFVKRVTHKgNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLdQFETRKTLILILELCSSEELLDr 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 -FLK---TDEGSRLSLprlidmsAQIAEGMAYIERMNSIHRDLRAANILV----SEALccKIADFGLARIID------SE 388
Cdd:cd14107  89 lFLKgvvTEAEVKLYI-------QQVLEGIGYLHGMNILHLDIKPDNILMvsptREDI--KICDFGFAQEITpsehqfSK 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 33469982 389 YTAQEgakfpikWTAPEAIHFGVFTIKADVWSFGVLLMEVVTYgRVPYPGMSNPEVIRNLERG 451
Cdd:cd14107 160 YGSPE-------FVAPEIVHQEPVSAATDIWALGVIAYLSLTC-HSPFAGENDRATLLNVAEG 214
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
233-450 4.45e-10

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 60.99  E-value: 4.45e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  233 EWEIprQSLRLVRKLGSGQFGEVWMGYYKNNMK-VAIKTLKEGTM----SPEAFLGEANVMKALQHERLVRLY-AVVTKE 306
Cdd:PTZ00263  14 SWKL--SDFEMGETLGTGSFGRVRIAKHKGTGEyYAIKCLKKREIlkmkQVQHVAQEKSILMELSHPFIVNMMcSFQDEN 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982  307 PIYIVTEYMARGCLLDFLKTdeGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLA-RII 385
Cdd:PTZ00263  92 RVYFLLEFVVGGELFTHLRK--AGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAkKVP 169
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469982  386 DSEYTAqegAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVtygrVPYPGMSNPEVIRNLER 450
Cdd:PTZ00263 170 DRTFTL---CGTP-EYLAPEVIQSKGHGKAVDWWTMGVLLYEFI----AGYPPFFDDTPFRIYEK 226
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
245-424 4.81e-10

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270987 [Multi-domain]  Cd Length: 294  Bit Score: 60.61  E-value: 4.81e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYK-NNMKVAIKTLKEgTMSPEAFLGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCLLD 322
Cdd:cd14085   9 SELGRGATSVVYRCRQKgTQKPYAVKKLKK-TVDKKIVRTEIGVLLRLSHPNIIKLKEIFeTPTEISLVLELVTGGELFD 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 flKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVS---EALCCKIADFGLARIIDSEYTAQEGAKFPi 399
Cdd:cd14085  88 --RIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYAtpaPDAPLKIADFGLSKIVDQQVTMKTVCGTP- 164
                       170       180
                ....*....|....*....|....*
gi 33469982 400 KWTAPEAIHFGVFTIKADVWSFGVL 424
Cdd:cd14085 165 GYCAPEILRGCAYGPEVDMWSVGVI 189
STKc_ROCK2 cd05621
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
244-436 4.83e-10

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270771 [Multi-domain]  Cd Length: 379  Bit Score: 61.17  E-value: 4.83e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTM---SPEAFLGEA-NVMKALQHERLVRLYAVVTKEP-IYIVTEYMAR 317
Cdd:cd05621  57 VKVIGRGAFGEVQLVRHKASQKVyAMKLLSKFEMikrSDSAFFWEErDIMAFANSPWVVQLFCAFQDDKyLYMVMEYMPG 136
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLktdegSRLSLPRLID--MSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQ-EG 394
Cdd:cd05621 137 GDLVNLM-----SNYDVPEKWAkfYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKYGHLKLADFGTCMKMDETGMVHcDT 211
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 33469982 395 AKFPIKWTAPEAIHF----GVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05621 212 AVGTPDYISPEVLKSqggdGYYGRECDWWSVGVFLFEMLV-GDTPF 256
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
247-440 5.70e-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: 60.39  E-value: 5.70e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYK-NNMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGcLL 321
Cdd:cd07848   9 VGEGAYGVVLKCRHKeTKEIVAIKKFKdseENEEVKETTLRELKMLRTLKQENIVELKeAFRRRGKLYLVFEYVEKN-ML 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 322 DFLktDEGSRLSLP-RLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPIK 400
Cdd:cd07848  88 ELL--EEMPNGVPPeKVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGSNANYTEYVATR 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 33469982 401 W-TAPEAIHFGVFTIKADVWSFGVLLMEvVTYGRVPYPGMS 440
Cdd:cd07848 166 WyRSPELLLGAPYGKAVDMWSVGCILGE-LSDGQPLFPGES 205
STKc_CK2_alpha cd14132
Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the ...
229-429 5.71e-10

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271034 [Multi-domain]  Cd Length: 306  Bit Score: 60.63  E-value: 5.71e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 229 WAQDEWEIPRQSL---RLVRKLGSGQFGEVWMGY-YKNNMKVAIKTLKegTMSPEAFLGEANVMKALQ-HERLVRLYAVV 303
Cdd:cd14132   5 WDYENLNVEWGSQddyEIIRKIGRGKYSEVFEGInIGNNEKVVIKVLK--PVKKKKIKREIKILQNLRgGPNIVKLLDVV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 304 ----TKEPIyIVTEYMARgclLDFLK-----TDEGSRLSLprlidmsAQIAEGMAYIERMNSIHRDLRAANILVSEA--- 371
Cdd:cd14132  83 kdpqSKTPS-LIFEYVNN---TDFKTlyptlTDYDIRYYM-------YELLKALDYCHSKGIMHRDVKPHNIMIDHEkrk 151
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33469982 372 LccKIADFGLAR--IIDSEYTAQEGAKFpikWTAPEA-IHFGVFTIKADVWSFGVLLMEVV 429
Cdd:cd14132 152 L--RLIDWGLAEfyHPGQEYNVRVASRY---YKGPELlVDYQYYDYSLDMWSLGCMLASMI 207
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
245-429 5.80e-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: 5.80e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVW-MGYYKNNMKVAIKTLK---EGTMSPEAFLGEANVMKALQHERLVRLYAVVTK------EPIYIVTEY 314
Cdd:cd07853   6 RPIGYGAFGVVWsVTDPRDGKRVALKKMPnvfQNLVSCKRVFRELKMLCFFKHDNVLSALDILQPphidpfEEIYVVTEL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 315 MARgcllDFLK--------TDEGSRLSLprlidmsAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIID 386
Cdd:cd07853  86 MQS----DLHKiivspqplSSDHVKVFL-------YQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEE 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 ---SEYTAQEGAKfpIKWTAPE----AIHfgvFTIKADVWSFGVLLMEVV 429
Cdd:cd07853 155 pdeSKHMTQEVVT--QYYRAPEilmgSRH---YTSAVDIWSVGCIFAELL 199
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
245-438 5.85e-10

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: 60.01  E-value: 5.85e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 245 RKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPEAFL--GEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMARGCL 320
Cdd:cd14183  12 RTIGDGNFAVVKECVERSTGREyALKIINKSKCRGKEHMiqNEVSILRRVKHPNIVLLIEEMdMPTELYLVMELVKGGDL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 321 LDFLKTdeGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSE----ALCCKIADFGLARIIDSEYTAQEGAK 396
Cdd:cd14183  92 FDAITS--TNKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVYEhqdgSKSLKLGDFGLATVVDGPLYTVCGTP 169
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 33469982 397 fpiKWTAPEAIHFGVFTIKADVWSFGVLLMeVVTYGRVPYPG 438
Cdd:cd14183 170 ---TYVAPEIIAETGYGLKVDIWAAGVITY-ILLCGFPPFRG 207
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
244-436 8.17e-10

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 60.48  E-value: 8.17e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 244 VRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPE----AFLGEANVMKALQHERLVRL-YAVVTKEPIYIVTEYMAR 317
Cdd:cd05593  20 LKLLGKGTFGKVILVREKASGKYyAMKILKKEVIIAKdevaHTLTESRVLKNTRHPFLTSLkYSFQTKDRLCFVMEYVNG 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLldFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR--IIDSEyTAQEGA 395
Cdd:cd05593 100 GEL--FFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKegITDAA-TMKTFC 176
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 33469982 396 KFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPY 436
Cdd:cd05593 177 GTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPF 215
SH3_SLAP cd12010
Src homology 3 domain of Src-Like Adaptor Protein; SLAP (or SLA1) modulates TCR surface ...
62-116 8.71e-10

Src homology 3 domain of Src-Like Adaptor Protein; SLAP (or SLA1) modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, c-Cbl, LAT, CD247, and Zap70, among others. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. The SH3 domain of SLAP forms a complex with v-Abl. 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: 212943  Cd Length: 55  Bit Score: 54.43  E-value: 8.71e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 33469982  62 FVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVARV 116
Cdd:cd12010   1 FLAVLADYPSPDISEPIFHMGEKLRVLSDEGGWWKVRSLQTGRENYIPGKCVAKV 55
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
246-448 8.81e-10

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: 59.49  E-value: 8.81e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 246 KLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY-AVVTKEPIYIVTEYMARGCLLDF 323
Cdd:cd14104   7 ELGRGQFGIVHRCVETSSKKTyMAKFVKVKGADQVLVKKEISILNIARHRNILRLHeSFESHEELVMIFEFISGVDIFER 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 324 LkTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANIlvseaLCC-------KIADFGLARiidseyTAQEGAK 396
Cdd:cd14104  87 I-TTARFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENI-----IYCtrrgsyiKIIEFGQSR------QLKPGDK 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 397 FPIKWT-----APEAIHFGVFTIKADVWSFGVLLMeVVTYGRVPYPGMSNPEVIRNL 448
Cdd:cd14104 155 FRLQYTsaefyAPEVHQHESVSTATDMWSLGCLVY-VLLSGINPFEAETNQQTIENI 210
STKc_MRCK_alpha cd05623
Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 ...
238-493 8.90e-10

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


Pssm-ID: 270773 [Multi-domain]  Cd Length: 409  Bit Score: 60.80  E-value: 8.90e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 238 RQSLRLVRKLGSGQFGEVWMGYYKNNMKV-AIKTLKEGTMSPEA----FLGEANVMKALQHERLVRL-YAVVTKEPIYIV 311
Cdd:cd05623  71 KEDFEILKVIGRGAFGEVAVVKLKNADKVfAMKILNKWEMLKRAetacFREERDVLVNGDSQWITTLhYAFQDDNNLYLV 150
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 312 TEYMARGCLLDFLKTDEGSrlsLPRliDMS----AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLARIIDS 387
Cdd:cd05623 151 MDYYVGGDLLTLLSKFEDR---LPE--DMArfylAEMVLAIDSVHQLHYVHRDIKPDNILMDMNGHIRLADFGSCLKLME 225
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 388 EYTAQEGAKFPI-KWTAPEAIHF-----GVFTIKADVWSFGVLLMEVVtYGRVPYPGMSNPEV---IRNLERGYRMPRPD 458
Cdd:cd05623 226 DGTVQSSVAVGTpDYISPEILQAmedgkGKYGPECDWWSLGVCMYEML-YGETPFYAESLVETygkIMNHKERFQFPTQV 304
                       250       260       270
                ....*....|....*....|....*....|....*
gi 33469982 459 TCPPELYRGVIAECWRSRpEERptfeFLQSVLEDF 493
Cdd:cd05623 305 TDVSENAKDLIRRLICSR-EHR----LGQNGIEDF 334
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
247-424 8.92e-10

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: 59.31  E-value: 8.92e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVWMGYYKNNMK-VAIKTL-------KEGTMSpeaflGEANVMKALQHERLVRLYAVV-TKEPIYIVTEYMAR 317
Cdd:cd14083  11 LGTGAFSEVVLAEDKATGKlVAIKCIdkkalkgKEDSLE-----NEIAVLRKIKHPNIVQLLDIYeSKSHLYLVMELVTG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 318 GCLLDFLkTDEGSRLSLprliDMSA---QIAEGMAYIERMNSIHRDLRAANIL-VSEALCCKI--ADFGLARIIDSEYTA 391
Cdd:cd14083  86 GELFDRI-VEKGSYTEK----DASHlirQVLEAVDYLHSLGIVHRDLKPENLLyYSPDEDSKImiSDFGLSKMEDSGVMS 160
                       170       180       190
                ....*....|....*....|....*....|...
gi 33469982 392 QegAKFPIKWTAPEAIHFGVFTIKADVWSFGVL 424
Cdd:cd14083 161 T--ACGTPGYVAPEVLAQKPYGKAVDCWSIGVI 191
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
247-451 9.83e-10

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


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 60.11  E-value: 9.83e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 247 LGSGQFGEVW---MGYYKNNMKV-AIKTLKEG--------TMSPEAflgEANVMKALQHERLVRL-YAVVTKEPIYIVTE 313
Cdd:cd05584   4 LGKGGYGKVFqvrKTTGSDKGKIfAMKVLKKAsivrnqkdTAHTKA---ERNILEAVKHPFIVDLhYAFQTGGKLYLILE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 YMARGCLLDFLKTdEGSRLSlprliDMS----AQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLariidSEY 389
Cdd:cd05584  81 YLSGGELFMHLER-EGIFME-----DTAcfylAEITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGL-----CKE 149
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33469982 390 TAQEGAK---F--PIKWTAPEAIHFGVFTIKADVWSFGVLLMEVVTyGRVPYPGMSNPEVIRNLERG 451
Cdd:cd05584 150 SIHDGTVthtFcgTIEYMAPEILTRSGHGKAVDWWSLGALMYDMLT-GAPPFTAENRKKTIDKILKG 215
STKc_ACVR2b cd14140
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ...
250-430 1.02e-09

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2b (or ActRIIB) 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. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors 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. The ACVR2b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271042 [Multi-domain]  Cd Length: 291  Bit Score: 59.66  E-value: 1.02e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 250 GQFGEVWMGYYKNNMkVAIKTLKegTMSPEAFLGEANVMK--ALQHERLVRLYAVVTK-----EPIYIVTEYMARGCLLD 322
Cdd:cd14140   6 GRFGCVWKAQLMNEY-VAVKIFP--IQDKQSWQSEREIFStpGMKHENLLQFIAAEKRgsnleMELWLITAFHDKGSLTD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 323 FLKtdeGSRLSLPRLIDMSAQIAEGMAYIE-----------RMNSIHRDLRAANILVSEALCCKIADFGLARIID----- 386
Cdd:cd14140  83 YLK---GNIVSWNELCHIAETMARGLSYLHedvprckgeghKPAIAHRDFKSKNVLLKNDLTAVLADFGLAVRFEpgkpp 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 33469982 387 SEYTAQEGAKfpiKWTAPE----AIHF--GVFtIKADVWSFGVLLMEVVT 430
Cdd:cd14140 160 GDTHGQVGTR---RYMAPEvlegAINFqrDSF-LRIDMYAMGLVLWELVS 205
PKc_DYRK cd14210
Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and ...
243-438 1.11e-09

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. 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. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.


Pssm-ID: 271112 [Multi-domain]  Cd Length: 311  Bit Score: 59.48  E-value: 1.11e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 243 LVRKLGSGQFGEVWMGY-YKNNMKVAIKTLK-EGTMSPEAfLGEANVMKALQH------ERLVRLYAVVT-KEPIYIVTE 313
Cdd:cd14210  17 VLSVLGKGSFGQVVKCLdHKTGQLVAIKIIRnKKRFHQQA-LVEVKILKHLNDndpddkHNIVRYKDSFIfRGHLCIVFE 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 314 ymargcLL-----DFLKTDEGSRLSLPrLIDM-SAQIAEGMAYIERMNSIHRDLRAANILVSEAL--CCKIADFGLA--- 382
Cdd:cd14210  96 ------LLsinlyELLKSNNFQGLSLS-LIRKfAKQILQALQFLHKLNIIHCDLKPENILLKQPSksSIKVIDFGSScfe 168
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33469982 383 --RI---IDSEYtaqegakfpikWTAPEAIhFGV-FTIKADVWSFGVLLMEVVTyGRVPYPG 438
Cdd:cd14210 169 geKVytyIQSRF-----------YRAPEVI-LGLpYDTAIDMWSLGCILAELYT-GYPLFPG 217
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
239-429 1.13e-09

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: 59.37  E-value: 1.13e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 239 QSLRLVRKLGSGQFGEVWMGyyKNNMKVAIKTLKEGTMSP-------EAFLGEANVMKALQHERLVRLYAVVTKEP-IYI 310
Cdd:cd05612   1 DDFERIKTIGTGTFGRVHLV--RDRISEHYYALKVMAIPEvirlkqeQHVHNEKRVLKEVSHPFIIRLFWTEHDQRfLYM 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469982 311 VTEYMARGCLLDFLKTdeGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRDLRAANILVSEALCCKIADFGLAR-IIDSEY 389
Cdd:cd05612  79 LMEYVPGGELFSYLRN--SGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKkLRDRTW 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 33469982 390 TAqegAKFPiKWTAPEAIHFGVFTIKADVWSFGVLLMEVV 429
Cdd:cd05612 157 TL---CGTP-EYLAPEVIQSKGHNKAVDWWALGILIYEML 192
 
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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