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Conserved domains on  [gi|2678964124|ref|XP_063121318.1|]
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macrophage-stimulating protein receptor isoform X4 [Rattus norvegicus]

Protein Classification

Sema_RON and IPT_plexin_repeat2 domain-containing protein( domain architecture ID 10181572)

protein containing domains Sema_RON, PSI, IPT_plexin_repeat2, and IPT

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Sema_RON cd11279
The Sema domain, a protein interacting module, of RON Receptor Tyrosine Kinase; RON receptor ...
29-549 0e+00

The Sema domain, a protein interacting module, of RON Receptor Tyrosine Kinase; RON receptor tyrosine kinase is a Macrophage-stimulating protein (MSP) receptor. Upon binding of MSP, RON is activated via autophosphorylation within its kinase catalytic domain, resulting in a wide range of effects, including proliferation, tubular morphogenesis, angiogenesis, cellular motility and invasiveness. By interacting with downstream signaling molecules, it regulates macrophage migration, phagocytosis, and nitric oxide production. RON has been implicated in cancers of the breast, colon, pancreas and ovaries because both splice variants and receptor overexpression have been identified in these tumors. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as ligand recognition and binding model. RON is 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 tyrosine kinase domain. The Sema domain of RON may be necessary for receptor dimerization and activation.


:

Pssm-ID: 200540 [Multi-domain]  Cd Length: 493  Bit Score: 797.07  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   29 WQCPRIPFAASRDFSVKYVVPSFSAGGRVQATAVYEDSknSAVFVAIRNRLHVLGPDLQYIESLTTGPIGDPGCQTCASC 108
Cdd:cd11279      1 WQCPRIPYALTRNFSVKYVVPSFSAGSPIQNIVSYEDA--SAVFVATRNHLHVLNPELKLLQNLVTGPTGSPGCQICALC 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  109 GPGPHGP-PNDTDTLVLVMEPGLPALVSCGSTLQGRCFLHELEPQGEALHLAAPACLFSASNNKPEACTDCVASHLGTRV 187
Cdd:cd11279     79 PPGPPGPsPEDTDNKVLVLDPEEPWLYSCGSSLHGRCFLHELESRGSAVHIASTACLFSANANKPSDCPDCVASPLGTRV 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  188 TVVEQGHASYFYVASSLDPELAASFSPRSVSIRRLKSDTSGFQPGFPSLSVLPKYLASYLIKYVHSFHSGDFVYFLTVQP 267
Cdd:cd11279    159 TVVEQSHTSYFYVASTLNSSVAASYSPRSVSIRRLKSDQDGFAPGFHSLTVLPKYLDSYPIHYVHSFTSGDFVYFLTVQP 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  268 MDVrsPPSALQTRLVRLNAIEPEIGDYRELVLDCHFAPKRRRRSGAPKSLQAYQVLQAAHSAPVDAKLALDLSISEGQEV 347
Cdd:cd11279    239 ESP--DSSAYHTRLVRLSAKEPELRDYRELVLDCRFEPKRRRRRRPAEREVPYNVLQAAHAAPVGSKLAVELGISEGQEV 316
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  348 LFGVFVAVKDSSSGP--NSVVCAFPINHLDNLIEEGVERCCHPSNSSLLtrRRGLDFFQTPSFCPNPPG----APSSRCH 421
Cdd:cd11279    317 LFGVFAESQPGSPVPqkNSAVCAFPISLLNEAIDEGMEKCCSSSNSDRL--FRGLDFFQPQSYCPHPPNlsaaVSNTSCW 394
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  422 YFPLMVHDSFTRVDLFNGLLGSVKVTALHVTRLGNVTVAHMGTEDGRILqvgpslshlvpqscplpllffseltclsQVE 501
Cdd:cd11279    395 NFPTLVSTSSFRVDLFNGHLSGVLLTSIYVTVLDNVTVAHLGTSDGRIL----------------------------QVV 446
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*...
gi 2678964124  502 IARSLNYLLYVSNFSLGsSGQPVHQDVSRLGNDLLFASGDQVFKVPIQ 549
Cdd:cd11279    447 LQRSLNYLLYVSNFSLG-DGQPVQRDVSRLGDSLLFASGNQVFKVNIT 493
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
1104-1315 2.83e-117

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 cd05058:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 262  Bit Score: 366.41  E-value: 2.83e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMR 1183
Cdd:cd05058      1 EVIGKGHFGCVYHGTLIDSDGQKIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPSEGSPLVVLPYMK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQRvsaqcpgwgvsasthlcrcspvsscpqNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05058     81 HGDLRNFIRSETH---------------------------NPTVKDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDE 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1264 SFTVKVADFGLARGILDKEYYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05058    134 SFTVKVADFGLARDIYDKEYYSVHNHTGAKLPVKWMALESLQTQKFTTKSDV 185
IPT_plexin_repeat2 cd01179
Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are ...
710-794 2.76e-27

Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present preceeded by SEMA (semaphorin) and PSI (plexin, semaphorin, integrin) domains.


:

Pssm-ID: 238584  Cd Length: 85  Bit Score: 106.54  E-value: 2.76e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  710 PMLTSIKPDFGPRAGGTYLTLEGQSLSVGTSRAVLVNGTQCRLEQVSEEKILCVTPPGAGTASVPLRLQIGGAEVRGSRT 789
Cdd:cd01179      1 PSITSLSPSYGPQSGGTRLTITGKHLNAGSSVRVTVGGQPCKILSVSSSQIVCLTPPSASPGEAPVKVLIDGARRLAPLV 80

                   ....*
gi 2678964124  790 FHYKE 794
Cdd:cd01179     81 FTYTE 85
IPT super family cl15674
Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as ...
595-709 6.01e-18

Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor receptors), as well as, cyclodextrin glycosyltransferase and similar enzymes. Although they are involved in DNA binding in transcription factors, their function in other proteins is unknown. In these transcription factors, IPTs form homo- or heterodimers with the exception of the nuclear factor of activated Tcells (NFAT) transcription factors which are mainly monomers.


The actual alignment was detected with superfamily member cd01180:

Pssm-ID: 472823  Cd Length: 94  Bit Score: 80.05  E-value: 6.01e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  595 PEITEFHPHSGPLRGTTRLTLCGSNFYLRPDGVvpegTHQITVGQSPCRLLP--KDSSTR------RSGSQkefieelec 666
Cdd:cd01180      1 PVITEFFPLSGPLEGGTRLTICGSNLGLRKNDV----RHGVRVGGVPCNPEPpeYSSSEKivcttgPAGNP--------- 67
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2678964124  667 elepletqaVGTTNISLLITNMPAGKHfrvegvsVREDFSFME 709
Cdd:cd01180     68 ---------VFNGPVEVTVGHGSFRTE-------SSEGFSFVD 94
IPT smart00429
ig-like, plexins, transcription factors;
795-856 1.35e-05

ig-like, plexins, transcription factors;


:

Pssm-ID: 214657 [Multi-domain]  Cd Length: 90  Bit Score: 44.72  E-value: 1.35e-05
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124   795 DPIVLDISPKCGY--SGSHVMVHGQHLTSAWHLTVSFNDGqsivESRCAGQFLEQQHQ-CRLPEY 856
Cdd:smart00429    1 DPVITRISPTSGPvsGGTEITLCGKNLKSISVVFVEVGVG----EAPCTFSPSSSTAIvCKTPPY 61
PSI pfam01437
Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The ...
552-594 3.83e-05

Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found Plexin. Two copies of the repeat are found in mahogany protein. A related C. elegans protein contains four copies of the repeat. The Met receptor contains a single copy of the repeat. The Pfam alignment shows 6 conserved cysteine residues that may form three conserved disulphide bridges, whereas some members show 8 conserved cysteines. The pattern of conservation suggests that cysteines 5 and 7 (that are not absolutely conserved) form a disulphide bridge (Personal observation. A Bateman).


:

Pssm-ID: 396154 [Multi-domain]  Cd Length: 52  Bit Score: 42.31  E-value: 3.83e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124  552 GCGHFLTCWRCLRAqRFMGCGWCGD--RCGRQKECPG------SWQQD--YCP 594
Cdd:pfam01437    1 RCSQYTSCSSCLAA-RDPYCGWCSSegRCVRRSACGApegnceEWEQAssKCP 52
 
Name Accession Description Interval E-value
Sema_RON cd11279
The Sema domain, a protein interacting module, of RON Receptor Tyrosine Kinase; RON receptor ...
29-549 0e+00

The Sema domain, a protein interacting module, of RON Receptor Tyrosine Kinase; RON receptor tyrosine kinase is a Macrophage-stimulating protein (MSP) receptor. Upon binding of MSP, RON is activated via autophosphorylation within its kinase catalytic domain, resulting in a wide range of effects, including proliferation, tubular morphogenesis, angiogenesis, cellular motility and invasiveness. By interacting with downstream signaling molecules, it regulates macrophage migration, phagocytosis, and nitric oxide production. RON has been implicated in cancers of the breast, colon, pancreas and ovaries because both splice variants and receptor overexpression have been identified in these tumors. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as ligand recognition and binding model. RON is 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 tyrosine kinase domain. The Sema domain of RON may be necessary for receptor dimerization and activation.


Pssm-ID: 200540 [Multi-domain]  Cd Length: 493  Bit Score: 797.07  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   29 WQCPRIPFAASRDFSVKYVVPSFSAGGRVQATAVYEDSknSAVFVAIRNRLHVLGPDLQYIESLTTGPIGDPGCQTCASC 108
Cdd:cd11279      1 WQCPRIPYALTRNFSVKYVVPSFSAGSPIQNIVSYEDA--SAVFVATRNHLHVLNPELKLLQNLVTGPTGSPGCQICALC 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  109 GPGPHGP-PNDTDTLVLVMEPGLPALVSCGSTLQGRCFLHELEPQGEALHLAAPACLFSASNNKPEACTDCVASHLGTRV 187
Cdd:cd11279     79 PPGPPGPsPEDTDNKVLVLDPEEPWLYSCGSSLHGRCFLHELESRGSAVHIASTACLFSANANKPSDCPDCVASPLGTRV 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  188 TVVEQGHASYFYVASSLDPELAASFSPRSVSIRRLKSDTSGFQPGFPSLSVLPKYLASYLIKYVHSFHSGDFVYFLTVQP 267
Cdd:cd11279    159 TVVEQSHTSYFYVASTLNSSVAASYSPRSVSIRRLKSDQDGFAPGFHSLTVLPKYLDSYPIHYVHSFTSGDFVYFLTVQP 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  268 MDVrsPPSALQTRLVRLNAIEPEIGDYRELVLDCHFAPKRRRRSGAPKSLQAYQVLQAAHSAPVDAKLALDLSISEGQEV 347
Cdd:cd11279    239 ESP--DSSAYHTRLVRLSAKEPELRDYRELVLDCRFEPKRRRRRRPAEREVPYNVLQAAHAAPVGSKLAVELGISEGQEV 316
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  348 LFGVFVAVKDSSSGP--NSVVCAFPINHLDNLIEEGVERCCHPSNSSLLtrRRGLDFFQTPSFCPNPPG----APSSRCH 421
Cdd:cd11279    317 LFGVFAESQPGSPVPqkNSAVCAFPISLLNEAIDEGMEKCCSSSNSDRL--FRGLDFFQPQSYCPHPPNlsaaVSNTSCW 394
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  422 YFPLMVHDSFTRVDLFNGLLGSVKVTALHVTRLGNVTVAHMGTEDGRILqvgpslshlvpqscplpllffseltclsQVE 501
Cdd:cd11279    395 NFPTLVSTSSFRVDLFNGHLSGVLLTSIYVTVLDNVTVAHLGTSDGRIL----------------------------QVV 446
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*...
gi 2678964124  502 IARSLNYLLYVSNFSLGsSGQPVHQDVSRLGNDLLFASGDQVFKVPIQ 549
Cdd:cd11279    447 LQRSLNYLLYVSNFSLG-DGQPVQRDVSRLGDSLLFASGNQVFKVNIT 493
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
1104-1315 2.83e-117

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: 366.41  E-value: 2.83e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMR 1183
Cdd:cd05058      1 EVIGKGHFGCVYHGTLIDSDGQKIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPSEGSPLVVLPYMK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQRvsaqcpgwgvsasthlcrcspvsscpqNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05058     81 HGDLRNFIRSETH---------------------------NPTVKDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDE 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1264 SFTVKVADFGLARGILDKEYYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05058    134 SFTVKVADFGLARDIYDKEYYSVHNHTGAKLPVKWMALESLQTQKFTTKSDV 185
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
1100-1315 8.78e-76

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: 251.65  E-value: 8.78e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQ-IHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPpEGLPRVL 1178
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLKGEGENTkIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQ-GEPLYIV 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMRHGDLLRFIRSPqrvsaqcpgwgvsasthlcrcspvsscPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:pfam07714   80 TEYMPGGDLLDFLRKH---------------------------KRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARN 132
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:pfam07714  133 CLVSENLVVKISDFGLSRDIYDDDYY--RKRGGGKLPIKWMAPESLKDGKFTSKSDV 187
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
1100-1315 1.07e-73

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: 245.92  E-value: 1.07e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  1100 IHTDQVIGKGHFGVVYHGEYTDEAQN-QIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVL 1178
Cdd:smart00221    1 LTLGKKLGEGAFGEVYKGTLKGKGDGkEVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPL-MIV 79
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  1179 LPYMRHGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:smart00221   80 MEYMPGGDLLDYLRKNR--------------------------PKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARN 133
                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124  1259 CMLDESFTVKVADFGLARGILDKEYYSVrqhRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:smart00221  134 CLVGENLVVKISDFGLSRDLYDDDYYKV---KGGKLPIRWMAPESLKEGKFTSKSDV 187
Sema smart00630
semaphorin domain;
65-525 2.37e-73

semaphorin domain;


Pssm-ID: 214747 [Multi-domain]  Cd Length: 390  Bit Score: 249.98  E-value: 2.37e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124    65 DSKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGDPgcQTCASCGPGPHGPPNDTDTLV-LVMEPGLPALVSCGSTL-QG 142
Cdd:smart00630    7 DEDNGTLYVGARNRLYQLSLNLILEAELKTGPVLSS--PDCEECVSKGKDPPTDCVNYIrLLLDYNEDRLLVCGTNAfQP 84
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   143 RCFLHELEpqgealhlaapaclfsasnnkpeactdcvashlgtrvtvveqghasYFYVASSLDPELAASFSPRSVSIRRL 222
Cdd:smart00630   85 VCRLRNLG----------------------------------------------ELYVGTVADFSGSDPAIPRSLSVRRL 118
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   223 KSDTsgfqpGFPSLSVLPKYLASYLIKYVHSFHSGDFVYFLTVQP-MDVRSPPSALQTRLVRL--------NAIEPEIGD 293
Cdd:smart00630  119 KGTS-----GVSLRTVLYDSKWLNEPNFVYAFESGDFVYFFFRETaVEDDNCGKAVHSRVARVckndvggpRSLDKKWTS 193
                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   294 YRELVLDCHFAPKRRRRsgapkslqaYQVLQAAHSAPVDaklaldlsiSEGQEVLFGVFVAVkdSSSGPNSVVCAFPINH 373
Cdd:smart00630  194 FLKARLECSVPGEDPFY---------FNELQAAFLLPPG---------SESDDVLYGVFSTS--SNPIPGSAVCAFSLSD 253
                           330       340       350       360       370       380       390       400
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   374 LDNLIEEGVERCCHPsNSSLLTRRRGLDFFQTPSFCPNPPGAPSS---------RCHYFPLMVHDSFTRVDLFNGLLGSV 444
Cdd:smart00630  254 INAVFNGPFKECETS-TSQWLPYSRGKVPYPRPGTCPNKPPSSKDlpdetlnfiKSHPLMDEVVQPLTGRPLFVKTDSNY 332
                           410       420       430       440       450       460       470       480
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   445 KVTALHVTRL---GNVTVAHMGTEDGRILQVgpslshLVPQScplpllffseltclsqveiaRSLNYLLYVSNFSLGSSG 521
Cdd:smart00630  333 LLTSIAVDRVatdGNYTVLFLGTSDGRILKV------VLSES--------------------SSSSESVVLEEISVFPDG 386

                    ....
gi 2678964124   522 QPVH 525
Cdd:smart00630  387 SPIS 390
IPT_plexin_repeat2 cd01179
Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are ...
710-794 2.76e-27

Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present preceeded by SEMA (semaphorin) and PSI (plexin, semaphorin, integrin) domains.


Pssm-ID: 238584  Cd Length: 85  Bit Score: 106.54  E-value: 2.76e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  710 PMLTSIKPDFGPRAGGTYLTLEGQSLSVGTSRAVLVNGTQCRLEQVSEEKILCVTPPGAGTASVPLRLQIGGAEVRGSRT 789
Cdd:cd01179      1 PSITSLSPSYGPQSGGTRLTITGKHLNAGSSVRVTVGGQPCKILSVSSSQIVCLTPPSASPGEAPVKVLIDGARRLAPLV 80

                   ....*
gi 2678964124  790 FHYKE 794
Cdd:cd01179     81 FTYTE 85
Sema pfam01403
Sema domain; The Sema domain occurs in semaphorins, which are a large family of secreted and ...
323-528 2.99e-21

Sema domain; The Sema domain occurs in semaphorins, which are a large family of secreted and transmembrane proteins, some of which function as repellent signals during axon guidance. Sema domains also occur in the hepatocyte growth factor receptor and Swiss:P51805


Pssm-ID: 460197 [Multi-domain]  Cd Length: 180  Bit Score: 92.33  E-value: 2.99e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  323 LQAAHSAPVDAKLALDlsisegqEVLFGVFVAVKdSSSGPNSVVCAFPINHLDNLIEeGVERCCHPSNSSLLtRRRGLDF 402
Cdd:pfam01403    1 LQDVFVLKPGAGDALD-------TVLYGVFTTQW-SNSIGGSAVCAFSLSDINAVFE-GPFKEQEKSDSKWL-PYTGKVP 70
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  403 FQTPSFCPNPP---GAPSSRC---HYFPLMVH--DSFTRVDLFNGllGSVKVTALHVTRL----GNVTVAHMGTEDGRIL 470
Cdd:pfam01403   71 YPRPGTCINDPlrlDLPDSVLnfvKDHPLMDEavQPVGGRPLLVR--TGVRLTSIAVDRVqaldGNYTVLFLGTDDGRLH 148
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124  471 QVgpslshlvpqscplpllffseltclsqveIARSLNYLLYVSNFSLGSSGQPVHQDV 528
Cdd:pfam01403  149 KV-----------------------------VLVGSEESHIIEEIQVFPEPQPVLNLL 177
IPT_plexin_repeat1 cd01180
First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are ...
595-709 6.01e-18

First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present preceeded by SEMA (semaphorin) and PSI (plexin, semaphorin, integrin) domains.


Pssm-ID: 238585  Cd Length: 94  Bit Score: 80.05  E-value: 6.01e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  595 PEITEFHPHSGPLRGTTRLTLCGSNFYLRPDGVvpegTHQITVGQSPCRLLP--KDSSTR------RSGSQkefieelec 666
Cdd:cd01180      1 PVITEFFPLSGPLEGGTRLTICGSNLGLRKNDV----RHGVRVGGVPCNPEPpeYSSSEKivcttgPAGNP--------- 67
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2678964124  667 elepletqaVGTTNISLLITNMPAGKHfrvegvsVREDFSFME 709
Cdd:cd01180     68 ---------VFNGPVEVTVGHGSFRTE-------SSEGFSFVD 94
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
1104-1315 2.01e-16

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 83.91  E-value: 2.01e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQnqiHCAIKSL--SRITEVQEVEAFLREGLIMRGLHHPNILALIGImLPPEGLPRVLLPY 1181
Cdd:COG0515     13 RLLGRGGMGVVYLARDLRLGR---PVALKVLrpELAADPEARERFRREARALARLNHPNIVRVYDV-GEEDGRPYLVMEY 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:COG0515     89 VEGESLADLLRRRGPLP----------------------------PAEALRILAQLAEALAAAHAAGIVHRDIKPANILL 140
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1262 DESFTVKVADFGLARgILDKEyySVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:COG0515    141 TPDGRVKLIDFGIAR-ALGGA--TLTQTGTVVGTPGYMAPEQARGEPVDPRSDV 191
IPT smart00429
ig-like, plexins, transcription factors;
709-792 7.91e-15

ig-like, plexins, transcription factors;


Pssm-ID: 214657 [Multi-domain]  Cd Length: 90  Bit Score: 70.91  E-value: 7.91e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   709 EPMLTSIKPDFGPRAGGTYLTLEGQSLSVGTSRAVLVNGTQ--CRLEQVSEEKILCVTPPGA-GTASVPLR-LQIGGAEV 784
Cdd:smart00429    1 DPVITRISPTSGPVSGGTEITLCGKNLKSISVVFVEVGVGEapCTFSPSSSTAIVCKTPPYHnIPGSVPVRtVGLRNGGV 80

                    ....*....
gi 2678964124   785 RGSR-TFHY 792
Cdd:smart00429   81 PSSPqPFTY 89
IPT smart00429
ig-like, plexins, transcription factors;
594-651 2.87e-11

ig-like, plexins, transcription factors;


Pssm-ID: 214657 [Multi-domain]  Cd Length: 90  Bit Score: 60.90  E-value: 2.87e-11
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124   594 PPEITEFHPHSGPLRGTTRLTLCGSNFylrpdGVVPEGTHQITVGQSPCRLLPKDSST 651
Cdd:smart00429    1 DPVITRISPTSGPVSGGTEITLCGKNL-----KSISVVFVEVGVGEAPCTFSPSSSTA 53
TIG pfam01833
IPT/TIG domain; This family consists of a domain that has an immunoglobulin like fold. These ...
710-792 4.30e-09

IPT/TIG domain; This family consists of a domain that has an immunoglobulin like fold. These domains are found in cell surface receptors such as Met and Ron as well as in intracellular transcription factors where it is involved in DNA binding. CAUTION: This family does not currently recognize a significant number of members.


Pssm-ID: 460355 [Multi-domain]  Cd Length: 84  Bit Score: 54.76  E-value: 4.30e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  710 PMLTSIKPDFGPRAGGTYLTLEGQSLSVGTSRA-VLVNGTQCRLEQVSEEKILCVTPPGAgTASVPLRLQIGGAEVRGSR 788
Cdd:pfam01833    1 PVITSISPSSGPASGGTTITITGSNFGTDSSDLkVTIGGTPCTVISVSSTTIVCTTPPGT-SGLVNVSVTVGGGGISSSP 79

                   ....*
gi 2678964124  789 -TFHY 792
Cdd:pfam01833   80 lTFTY 84
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
1106-1276 7.17e-09

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 59.00  E-value: 7.17e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgEYTDEAQNQIhCAIK-------SLSRITEVQEVE------AFLREGLIMRGLHHPNILALIGIMLPpE 1172
Cdd:PTZ00024    17 LGEGTYGKVE--KAYDTLTGKI-VAIKkvkiieiSNDVTKDRQLVGmcgihfTTLRELKIMNEIKHENIMGLVDVYVE-G 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 GLPRVLLPYMrHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqNPTVKDLIsfgLQVACGMEYLAEQKFVHR 1252
Cdd:PTZ00024    93 DFINLVMDIM-ASDLKKVVDRKIRLT-------------------------ESQVKCIL---LQILNGLNVLHKWYFMHR 143
                          170       180
                   ....*....|....*....|....
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLAR 1276
Cdd:PTZ00024   144 DLSPANIFINSKGICKIADFGLAR 167
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
1225-1276 7.75e-06

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 50.18  E-value: 7.75e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1225 PTVKDLI------------SFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:NF033483    92 RTLKDYIrehgplspeeavEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIAR 155
IPT smart00429
ig-like, plexins, transcription factors;
795-856 1.35e-05

ig-like, plexins, transcription factors;


Pssm-ID: 214657 [Multi-domain]  Cd Length: 90  Bit Score: 44.72  E-value: 1.35e-05
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124   795 DPIVLDISPKCGY--SGSHVMVHGQHLTSAWHLTVSFNDGqsivESRCAGQFLEQQHQ-CRLPEY 856
Cdd:smart00429    1 DPVITRISPTSGPvsGGTEITLCGKNLKSISVVFVEVGVG----EAPCTFSPSSSTAIvCKTPPY 61
PSI pfam01437
Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The ...
552-594 3.83e-05

Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found Plexin. Two copies of the repeat are found in mahogany protein. A related C. elegans protein contains four copies of the repeat. The Met receptor contains a single copy of the repeat. The Pfam alignment shows 6 conserved cysteine residues that may form three conserved disulphide bridges, whereas some members show 8 conserved cysteines. The pattern of conservation suggests that cysteines 5 and 7 (that are not absolutely conserved) form a disulphide bridge (Personal observation. A Bateman).


Pssm-ID: 396154 [Multi-domain]  Cd Length: 52  Bit Score: 42.31  E-value: 3.83e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124  552 GCGHFLTCWRCLRAqRFMGCGWCGD--RCGRQKECPG------SWQQD--YCP 594
Cdd:pfam01437    1 RCSQYTSCSSCLAA-RDPYCGWCSSegRCVRRSACGApegnceEWEQAssKCP 52
TIG pfam01833
IPT/TIG domain; This family consists of a domain that has an immunoglobulin like fold. These ...
595-651 6.33e-04

IPT/TIG domain; This family consists of a domain that has an immunoglobulin like fold. These domains are found in cell surface receptors such as Met and Ron as well as in intracellular transcription factors where it is involved in DNA binding. CAUTION: This family does not currently recognize a significant number of members.


Pssm-ID: 460355 [Multi-domain]  Cd Length: 84  Bit Score: 40.12  E-value: 6.33e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124  595 PEITEFHPHSGPLRGTTRLTLCGSNFYLRPDGVvpegthQITVGQSPCRLLPKDSST 651
Cdd:pfam01833    1 PVITSISPSSGPASGGTTITITGSNFGTDSSDL------KVTIGGTPCTVISVSSTT 51
PSI smart00423
domain found in Plexins, Semaphorins and Integrins;
552-594 1.81e-03

domain found in Plexins, Semaphorins and Integrins;


Pssm-ID: 214655 [Multi-domain]  Cd Length: 47  Bit Score: 37.52  E-value: 1.81e-03
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 2678964124   552 GCGHFLTCWRCLRAQRFmGCGWC--GDRCGRQKECPGS---WQQDYCP 594
Cdd:smart00423    1 RCSKYTSCSECLLARDP-YCAWCssQGRCTSGERCDSRrqnWLSGGCP 47
IPT cd00102
Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as ...
796-888 5.31e-03

Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor receptors), as well as, cyclodextrin glycosyltransferase and similar enzymes. Although they are involved in DNA binding in transcription factors, their function in other proteins is unknown. In these transcription factors, IPTs form homo- or heterodimers with the exception of the nuclear factor of activated Tcells (NFAT) transcription factors which are mainly monomers.


Pssm-ID: 238050 [Multi-domain]  Cd Length: 89  Bit Score: 37.44  E-value: 5.31e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  796 PIVLDISPKCG--YSGSHVMVHGQHLTSAWHLTVSFNDGQSIVESRCagqfleQQHQ--CRLPEYmvrNPQGWATGNLSL 871
Cdd:cd00102      1 PVITSISPSSGpvSGGTEVTITGSNFGSGSNLRVTFGGGVPCSVLSV------SSTAivCTTPPY---ANPGPGPVEVTV 71
                           90
                   ....*....|....*...
gi 2678964124  872 -WGDGAAGFTLPGFRFLP 888
Cdd:cd00102     72 dRGNGGITSSPLTFTYVP 89
 
Name Accession Description Interval E-value
Sema_RON cd11279
The Sema domain, a protein interacting module, of RON Receptor Tyrosine Kinase; RON receptor ...
29-549 0e+00

The Sema domain, a protein interacting module, of RON Receptor Tyrosine Kinase; RON receptor tyrosine kinase is a Macrophage-stimulating protein (MSP) receptor. Upon binding of MSP, RON is activated via autophosphorylation within its kinase catalytic domain, resulting in a wide range of effects, including proliferation, tubular morphogenesis, angiogenesis, cellular motility and invasiveness. By interacting with downstream signaling molecules, it regulates macrophage migration, phagocytosis, and nitric oxide production. RON has been implicated in cancers of the breast, colon, pancreas and ovaries because both splice variants and receptor overexpression have been identified in these tumors. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as ligand recognition and binding model. RON is 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 tyrosine kinase domain. The Sema domain of RON may be necessary for receptor dimerization and activation.


Pssm-ID: 200540 [Multi-domain]  Cd Length: 493  Bit Score: 797.07  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   29 WQCPRIPFAASRDFSVKYVVPSFSAGGRVQATAVYEDSknSAVFVAIRNRLHVLGPDLQYIESLTTGPIGDPGCQTCASC 108
Cdd:cd11279      1 WQCPRIPYALTRNFSVKYVVPSFSAGSPIQNIVSYEDA--SAVFVATRNHLHVLNPELKLLQNLVTGPTGSPGCQICALC 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  109 GPGPHGP-PNDTDTLVLVMEPGLPALVSCGSTLQGRCFLHELEPQGEALHLAAPACLFSASNNKPEACTDCVASHLGTRV 187
Cdd:cd11279     79 PPGPPGPsPEDTDNKVLVLDPEEPWLYSCGSSLHGRCFLHELESRGSAVHIASTACLFSANANKPSDCPDCVASPLGTRV 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  188 TVVEQGHASYFYVASSLDPELAASFSPRSVSIRRLKSDTSGFQPGFPSLSVLPKYLASYLIKYVHSFHSGDFVYFLTVQP 267
Cdd:cd11279    159 TVVEQSHTSYFYVASTLNSSVAASYSPRSVSIRRLKSDQDGFAPGFHSLTVLPKYLDSYPIHYVHSFTSGDFVYFLTVQP 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  268 MDVrsPPSALQTRLVRLNAIEPEIGDYRELVLDCHFAPKRRRRSGAPKSLQAYQVLQAAHSAPVDAKLALDLSISEGQEV 347
Cdd:cd11279    239 ESP--DSSAYHTRLVRLSAKEPELRDYRELVLDCRFEPKRRRRRRPAEREVPYNVLQAAHAAPVGSKLAVELGISEGQEV 316
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  348 LFGVFVAVKDSSSGP--NSVVCAFPINHLDNLIEEGVERCCHPSNSSLLtrRRGLDFFQTPSFCPNPPG----APSSRCH 421
Cdd:cd11279    317 LFGVFAESQPGSPVPqkNSAVCAFPISLLNEAIDEGMEKCCSSSNSDRL--FRGLDFFQPQSYCPHPPNlsaaVSNTSCW 394
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  422 YFPLMVHDSFTRVDLFNGLLGSVKVTALHVTRLGNVTVAHMGTEDGRILqvgpslshlvpqscplpllffseltclsQVE 501
Cdd:cd11279    395 NFPTLVSTSSFRVDLFNGHLSGVLLTSIYVTVLDNVTVAHLGTSDGRIL----------------------------QVV 446
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*...
gi 2678964124  502 IARSLNYLLYVSNFSLGsSGQPVHQDVSRLGNDLLFASGDQVFKVPIQ 549
Cdd:cd11279    447 LQRSLNYLLYVSNFSLG-DGQPVQRDVSRLGDSLLFASGNQVFKVNIT 493
Sema_MET_like cd11248
The Sema domain, a protein interacting module, of MET and RON receptor tyrosine kinases; This ...
48-549 0e+00

The Sema domain, a protein interacting module, of MET and RON receptor tyrosine kinases; This family includes MET and RON receptor tyrosine kinases. MET is encoded by the c-met protooncogene. MET is the receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF and MET regulates multiple cellular events and are essential for the development of several tissues and organs, including the placenta, liver, and several groups of skeletal muscles. RON receptor tyrosine kinase is a Macrophage-stimulating protein (MSP) receptor. Upon binding of MSP, RON is activated via autophosphorylation within its kinase catalytic domain, resulting in a variety of effects including proliferation, tubular morphogenesis, angiogenesis, cellular motility and invasiveness. By interacting with downstream signaling molecules, it regulates macrophage migration, phagocytosis, and nitric oxide production. MET and RON receptors have been implicated in cancer development and migration. They are composed of alpha-beta heterodimers. 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 tyrosine kinase domain. The Sema domain is necessary for receptor dimerization and activation.


Pssm-ID: 200509 [Multi-domain]  Cd Length: 467  Bit Score: 619.44  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   48 VPSFSAGGRVQATAVYEDSknSAVFVAIRNRLHVLGPDLQYIESLTTGPIGDPGCQTCASCGPGP-HGPPNDTDTLVLVM 126
Cdd:cd11248      1 LPFFTADTPIQNIVLNEGS--TEVYVAAQNVIYALNPDLQKVWEYKTGPVGSPDCQTCQDCSSGAdPGVPKDTDNMVLVL 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  127 EPGL-PALVSCGSTLQGRCFLHELEPqgEALHLAAPACLFSASNNKPEACTDCVASHLGTRVTVVEQGHASYFYVASSLD 205
Cdd:cd11248     79 ETYYdDYLYSCGSTQNGVCYRHVLED--GADIQSEVHCLFSKKNNSPSYCPDCVASPLGTKVTNVESGRTIYFFVANSVN 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  206 PELAASFSPRSVSIRRLKSDTSGFQPGFPSLSVLPKYLASYLIKYVHSFHSGDFVYFLTVQPMDVRSPPSALQTRLVRLN 285
Cdd:cd11248    157 SSLAGSFPPHSISVRRLKEDGFGFLSDQSYLDVLPSLRDSYPIKYVYSFHSGPFVYFLTVQRESLTKPSSAFHTRLVRLC 236
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  286 AIEPEIGDYRELVLDCHFAPKRRRRSGAPKslQAYQVLQAAHSAPVDAKLALDLSISEGQEVLFGVFVAVKDSSSGP--N 363
Cdd:cd11248    237 SSDSEIWRYREMPLECIFTPKRRRRSTEED--VVYNVLQAAHVSKVGADLADELGASEGDDILFGVFARSKPDSGEPmpN 314
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  364 SVVCAFPINHLDNLIEEGVERCCHPSNSSlLTRRRGLDFFQtPSFCPNPPGAPSSRCHYFPLMVHDSFtRVDLFNGLLGS 443
Cdd:cd11248    315 SALCAFPIKYVNDAIEKGVEKCCTSGLEH-FSGSLCHFQPC-PTCPGESSSCEATCKEYRTEVTKPYQ-RVDLFNGQMSN 391
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  444 VKVTALHVTRLGNVTVAHMGTEDGRILqvgpslshlvpqscplpllffseltclsQVEIARSLNylLYVSNFSLGSsgQP 523
Cdd:cd11248    392 VLLTSILVTTIGNHTVAHLGTSDGRVL----------------------------QVVLSRSGP--IPHVNFSLDS--QP 439
                          490       500
                   ....*....|....*....|....*...
gi 2678964124  524 VHQDVSRLG--NDLLFASGDQVFKVPIQ 549
Cdd:cd11248    440 VSREVAVLSsnGSLLFVTGDKITKVPLI 467
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
1104-1315 2.83e-117

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: 366.41  E-value: 2.83e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMR 1183
Cdd:cd05058      1 EVIGKGHFGCVYHGTLIDSDGQKIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPSEGSPLVVLPYMK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQRvsaqcpgwgvsasthlcrcspvsscpqNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05058     81 HGDLRNFIRSETH---------------------------NPTVKDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDE 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1264 SFTVKVADFGLARGILDKEYYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05058    134 SFTVKVADFGLARDIYDKEYYSVHNHTGAKLPVKWMALESLQTQKFTTKSDV 185
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
1100-1315 8.78e-76

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: 251.65  E-value: 8.78e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQ-IHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPpEGLPRVL 1178
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLKGEGENTkIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQ-GEPLYIV 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMRHGDLLRFIRSPqrvsaqcpgwgvsasthlcrcspvsscPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:pfam07714   80 TEYMPGGDLLDFLRKH---------------------------KRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARN 132
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:pfam07714  133 CLVSENLVVKISDFGLSRDIYDDDYY--RKRGGGKLPIKWMAPESLKDGKFTSKSDV 187
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
1105-1315 2.30e-74

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: 247.84  E-value: 2.30e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRH 1184
Cdd:cd00192      2 KLGEGAFGEVYKGKLKGGDGKTVDVAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPL-YLVMEYMEG 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSpqrvsaqcpgwgvsasthlCRCSPVSSCPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd00192     81 GDLLDFLRK-------------------SRPVFPSPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGED 141
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1265 FTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd00192    142 LVVKISDFGLSRDIYDDDYY--RKKTGGKLPIRWMAPESLKDGIFTSKSDV 190
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
1100-1315 1.07e-73

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: 245.92  E-value: 1.07e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  1100 IHTDQVIGKGHFGVVYHGEYTDEAQN-QIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVL 1178
Cdd:smart00221    1 LTLGKKLGEGAFGEVYKGTLKGKGDGkEVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPL-MIV 79
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  1179 LPYMRHGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:smart00221   80 MEYMPGGDLLDYLRKNR--------------------------PKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARN 133
                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124  1259 CMLDESFTVKVADFGLARGILDKEYYSVrqhRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:smart00221  134 CLVGENLVVKISDFGLSRDLYDDDYYKV---KGGKLPIRWMAPESLKEGKFTSKSDV 187
Sema smart00630
semaphorin domain;
65-525 2.37e-73

semaphorin domain;


Pssm-ID: 214747 [Multi-domain]  Cd Length: 390  Bit Score: 249.98  E-value: 2.37e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124    65 DSKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGDPgcQTCASCGPGPHGPPNDTDTLV-LVMEPGLPALVSCGSTL-QG 142
Cdd:smart00630    7 DEDNGTLYVGARNRLYQLSLNLILEAELKTGPVLSS--PDCEECVSKGKDPPTDCVNYIrLLLDYNEDRLLVCGTNAfQP 84
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   143 RCFLHELEpqgealhlaapaclfsasnnkpeactdcvashlgtrvtvveqghasYFYVASSLDPELAASFSPRSVSIRRL 222
Cdd:smart00630   85 VCRLRNLG----------------------------------------------ELYVGTVADFSGSDPAIPRSLSVRRL 118
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   223 KSDTsgfqpGFPSLSVLPKYLASYLIKYVHSFHSGDFVYFLTVQP-MDVRSPPSALQTRLVRL--------NAIEPEIGD 293
Cdd:smart00630  119 KGTS-----GVSLRTVLYDSKWLNEPNFVYAFESGDFVYFFFRETaVEDDNCGKAVHSRVARVckndvggpRSLDKKWTS 193
                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   294 YRELVLDCHFAPKRRRRsgapkslqaYQVLQAAHSAPVDaklaldlsiSEGQEVLFGVFVAVkdSSSGPNSVVCAFPINH 373
Cdd:smart00630  194 FLKARLECSVPGEDPFY---------FNELQAAFLLPPG---------SESDDVLYGVFSTS--SNPIPGSAVCAFSLSD 253
                           330       340       350       360       370       380       390       400
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   374 LDNLIEEGVERCCHPsNSSLLTRRRGLDFFQTPSFCPNPPGAPSS---------RCHYFPLMVHDSFTRVDLFNGLLGSV 444
Cdd:smart00630  254 INAVFNGPFKECETS-TSQWLPYSRGKVPYPRPGTCPNKPPSSKDlpdetlnfiKSHPLMDEVVQPLTGRPLFVKTDSNY 332
                           410       420       430       440       450       460       470       480
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   445 KVTALHVTRL---GNVTVAHMGTEDGRILQVgpslshLVPQScplpllffseltclsqveiaRSLNYLLYVSNFSLGSSG 521
Cdd:smart00630  333 LLTSIAVDRVatdGNYTVLFLGTSDGRILKV------VLSES--------------------SSSSESVVLEEISVFPDG 386

                    ....
gi 2678964124   522 QPVH 525
Cdd:smart00630  387 SPIS 390
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
1100-1315 1.08e-72

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 242.82  E-value: 1.08e-72
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  1100 IHTDQVIGKGHFGVVYHGEYTDEAQN-QIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVL 1178
Cdd:smart00219    1 LTLGKKLGEGAFGEVYKGKLKGKGGKkKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPL-YIV 79
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  1179 LPYMRHGDLLRFIRSPQRvsaqcpgwgvsasthlcrcspvsscpqNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:smart00219   80 MEYMEGGDLLSYLRKNRP---------------------------KLSLSDLLSFALQIARGMEYLESKNFIHRDLAARN 132
                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124  1259 CMLDESFTVKVADFGLARGILDKEYYSVrqhRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:smart00219  133 CLVGENLVVKISDFGLSRDLYDDDYYRK---RGGKLPIRWMAPESLKEGKFTSKSDV 186
Sema_MET cd11278
The Sema domain, a protein interacting module, of MET (also called hepatocyte growth factor ...
30-479 7.46e-64

The Sema domain, a protein interacting module, of MET (also called hepatocyte growth factor receptor, HGFR); MET is encoded by the c-met protooncogene. MET is a receptor tyrosine kinase that binds its ligand, hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF and MET are essential for the development of several tissues and organs, including the placenta, liver, and several groups of skeletal muscles. It also plays a major role in the abnormal migration of cancer cells as a result of overexpression or MET mutations. MET is 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 tyrosine kinase domain. The cytoplasmic C-terminal region acts as a docking site for multiple protein substrates, including Grb2, Gab1, STAT3, Shc, SHIP-1 and Src. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. The Sema domain of Met is necessary for receptor dimerization and activation.


Pssm-ID: 200539 [Multi-domain]  Cd Length: 492  Bit Score: 225.90  E-value: 7.46e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   30 QCPRIPFAASRDFSVKYVVPSFSAGGRVQATAVYEDSknsaVFVAIRNRLHVLGPDLQYIESLTTGPI-GDPGCQTCASC 108
Cdd:cd11278      1 QCKEAAKKSEMNLNMKYQLPNFTAETPIQNVILHKHH----IYVGAVNKIYVLNEDLQKVSEYKTGPVlEHPDCFPCQDC 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  109 GPG---PHGPPNDTDTLVLVMEPGLP-ALVSCGSTLQGRCFLHELEPQGEALHLAAPACLFSAS-NNKPEACTDCVASHL 183
Cdd:cd11278     77 SDKanlSNGVWKDNVNMALFVETYYDdQLISCGSVNRGTCQRHVFPHDHPADIQSEVHCIYSPQiEEEPDQCPDCVVSTL 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  184 GTRVTVVEQGHASYFYVASSLDPELAASFSPRSVSIRRLKSDTSGFQ--PGFPSLSVLPKYLASYLIKYVHSFHSGDFVY 261
Cdd:cd11278    157 GSKVLVTVKDRFVNFFVGNTINSSYFPDHPLHSISVRRLKETQDGFEflTDQSYIDVLPEFRDSYPIKYVHAFESNNFVY 236
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  262 FLTVQPMDVRSppSALQTRLVRLNAIEPEIGDYRELVLDCHFAPKRRRRSGAPkslQAYQVLQAAHSAPVDAKLALDLSI 341
Cdd:cd11278    237 FLTVQRESLDS--QTFHTRIIRFCSIDSELRSYMEMPLECIFTEKRRKRSTKK---EVFNILQAAYVSKPGAQLAREMGA 311
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  342 SEGQEVLFGVFVAVKDSSSGPN--SVVCAFPINHLDNLIEEGVE----RCCH----PSNSSLLTRRrgldFFQTPSFCpn 411
Cdd:cd11278    312 SLNDDILFGVFAQSKPDSAEPMnrSAVCAVSIKTINEFFNKIVDkqnvKCLQhfygKNHEHCFNRT----FLRNASYC-- 385
                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124  412 ppgapSSRCHYFPLMVHDSFTRVDLFNGLLGSVKVTALHVTRLGNVTVAHMGTEDGRILQV-----GPSLSHL 479
Cdd:cd11278    386 -----EARRDEYRVEVTTALQRVDLFMGQFSNVLLTSISVFTKGDLTIANLGTSEGRFMQVvvsrsGPSTPHV 453
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
1104-1315 1.06e-54

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: 191.98  E-value: 1.06e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLS-RITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGL-----PRV 1177
Cdd:cd05035      5 KILGEGEFGSVMEAQLKQDDGSQLKVAVKTMKvDIHTYSEIEEFLSEAACMKDFDHPNVMRLIGVCFTASDLnkppsPMV 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd05035     85 ILPFMKHGDLHSYLLY----------------------SRLGGLPEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAAR 142
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1258 NCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05035    143 NCMLDENMTVCVADFGLSRKIYSGDYY--RQGRISKMPVKWIALESLADNVYTSKSDV 198
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
1088-1315 2.90e-49

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: 177.03  E-value: 2.90e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1088 VKDVLIPHEQVVIhtDQVIGKGHFGVVYHGEYTDEAQNQIHCAIKSL-SRITEVQEVEAFLREGLIMRGLHHPNILALIG 1166
Cdd:cd05074      1 LKDVLIQEQQFTL--GRMLGKGEFGSVREAQLKSEDGSFQKVAVKMLkADIFSSSDIEEFLREAACMKEFDHPNVIKLIG 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1167 IML--PPEG---LPRVLLPYMRHGDLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVKDLISFGLQVACGM 1241
Cdd:cd05074     79 VSLrsRAKGrlpIPMVILPFMKHGDLHTFLLM----------------------SRIGEEPFTLPLQTLVRFMIDIASGM 136
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1242 EYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05074    137 EYLSSKNFIHRDLAARNCMLNENMTVCVADFGLSKKIYSGDYY--RQGCASKLPVKWLALESLADNVYTTHSDV 208
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
1100-1315 8.83e-48

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: 172.14  E-value: 8.83e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQ--IHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPpEGLPRV 1177
Cdd:cd05032      8 ITLIRELGQGSFGMVYEGLAKGVVKGEpeTRVAIKTVNENASMRERIEFLNEASVMKEFNCHHVVRLLGVVST-GQPTLV 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRSPQRVSAQCPGWGVsasthlcrcspvsscpqnPTVKDLISFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd05032     87 VMELMAKGDLKSYLRSRRPEAENNPGLGP------------------PTLQKFIQMAAEIADGMAYLAAKKFVHRDLAAR 148
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1258 NCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05032    149 NCMVAEDLTVKIGDFGMTRDIYETDYY--RKGGKGLLPVRWMAPESLKDGVFTTKSDV 204
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
1104-1315 9.75e-45

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: 163.64  E-value: 9.75e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEaQNQIHCAIKSLS-RITEVQEVEAFLREGLIMRGLHHPNILALIGIML---PPEGLPR--V 1177
Cdd:cd05075      6 KTLGEGEFGSVMEGQLNQD-DSVLKVAVKTMKiAICTRSEMEDFLSEAVCMKEFDHPNVMRLIGVCLqntESEGYPSpvV 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd05075     85 ILPFMKHGDLHSFLLY----------------------SRLGDCPVYLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAAR 142
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1258 NCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05075    143 NCMLNENMNVCVADFGLSKKIYNGDYY--RQGRISKMPVKWIAIESLADRVYTTKSDV 198
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
1090-1315 1.26e-44

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: 163.57  E-value: 1.26e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1090 DVLIphEQVVIHTDQVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQ-EVEAFLREGLIMRGLHHPNILALIGIM 1168
Cdd:cd14204      1 DVMI--DRNLLSLGKVLGEGEFGSVMEGELQQPDGTNHKVAVKTMKLDNFSQrEIEEFLSEAACMKDFNHPNVIRLLGVC 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1169 LP--PEGLPR--VLLPYMRHGDLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVKDLISFGLQVACGMEYL 1244
Cdd:cd14204     79 LEvgSQRIPKpmVILPFMKYGDLHSFLLR----------------------SRLGSGPQHVPLQTLLKFMIDIALGMEYL 136
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1245 AEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14204    137 SSRNFLHRDLAARNCMLRDDMTVCVADFGLSKKIYSGDYY--RQGRIAKMPVKWIAVESLADRVYTVKSDV 205
Sema_plexin_like cd11236
The Sema domain, a protein interacting module, of Plexins and MET-like receptor tyrosine ...
71-549 8.14e-44

The Sema domain, a protein interacting module, of Plexins and MET-like receptor tyrosine kinases; Plexins form a conserved family of transmembrane receptors for semaphorins and may be the ancestor of semaphorins. Ligand binding activates signal transduction pathways controlling axon guidance in the nervous system and other developmental processes including cell migration and morphogenesis, immune function, and tumor progression. Plexins are divided into four types (A-D) according to sequence similarity. In vertebrates, type A Plexins serve as the co-receptors for neuropilins to mediate the signalling of class 3 semaphorins except Sema3E, which signals through Plexin D1. Plexins serve as direct receptors for several other members of the semaphorin family: class 6 semaphorins signal through type A plexins and class 4 semaphorins through type B. Plexin C1 serves as the receptor of Sema7A and plays regulation roles in both immune and nervous systems. This family also includes the Met and RON receptor tyrosine kinases. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200497 [Multi-domain]  Cd Length: 401  Bit Score: 164.81  E-value: 8.14e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   71 VFVAIRNRLHVLGPDLQYIESLTTGPIGD-PGCQTCASCGPGPHGPPNDTDTLVLVMEPGLPALVSCGSTLQGRCFLHEL 149
Cdd:cd11236     14 VYVGAVNRLYQLDSSLLLEAEVSTGPVLDsPLCLPPGCCSCDHPRSPTDNYNKILLIDYSSGRLITCGSLYQGVCQLRNL 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  150 EPQGEALHlaapaclfsaSNNKPEACTDCVASHLGTrVTVVEQGHASYFYVASSLDPElaASFSPR-SVSIRRLKSDTSG 228
Cdd:cd11236     94 SNISVVVE----------RSSTPVAANDPNASTVGF-VGPGPYNNENVLYVGATYTNN--GYRDYRpAVSSRSLPPDDDF 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  229 FQPGF---PSLSVLPKYLASYLIKYVHSFHSGDFVYFLTVQPmDVRSPPSALQTRLVRLNAIEPEIGDYRELVLDChfap 305
Cdd:cd11236    161 NAGSLtggSAISIDDEYRDRYSIKYVYGFSSGGFSYFVTVQR-KSVDDESPYISRLVRVCQSDSNYYSYTEVPLQC---- 235
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  306 krRRRSGApkslqAYQVLQAAHSAPVDAKLALDLSISEGQEVLFGVFVAVKDSSSGP--NSVVCAFPINHldnlIEEGVE 383
Cdd:cd11236    236 --TGGDGT-----NYNLLQAAYVGKAGSDLARSLGISTDDDVLFGVFSKSKGPSAEPssKSALCVFSMKD----IEAAFN 304
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  384 RCCHPSNSSLLTrrrgldffqTPSFCPNppgapssrchyfplmvhdsftrvdlfngllgsVKVTALHVTRLGNVTVAHMG 463
Cdd:cd11236    305 DNCPLGGGVPIT---------TSAVLSD--------------------------------SLLTSVAVTTTRNHTVAFLG 343
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  464 TEDGRILQVgpslsHLVPQSCPLPllffseltclsqveiarslnYllyvSNFSLGsSGQPVHQDVsRLGNDLLF---ASG 540
Cdd:cd11236    344 TSDGQLKKV-----VLESSSSATQ--------------------Y----ETLLVD-SGSPILPDM-VFDPDGEHlyvMTP 392

                   ....*....
gi 2678964124  541 DQVFKVPIQ 549
Cdd:cd11236    393 KKVTKVPVE 401
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
1106-1315 8.28e-44

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: 161.00  E-value: 8.28e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGE--YTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEglPR-VLLPYM 1182
Cdd:cd05048     13 LGEGAFGKVYKGEllGPSSEESAISVAIKTLKENASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKEQ--PQcMLFEYM 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFI--RSPQR-VSAQCPGWGVSastHLCRCSpvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd05048     91 AHGDLHEFLvrHSPHSdVGVSSDDDGTA---SSLDQS------------DFLHIAIQIAAGMEYLSSHHYVHRDLAARNC 155
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1260 MLDESFTVKVADFGLARGILDKEYYSVrQHRhARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05048    156 LVGDGLTVKISDFGLSRDIYSSDYYRV-QSK-SLLPVRWMPPEAILYGKFTTESDV 209
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
1106-1315 6.50e-43

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: 157.96  E-value: 6.50e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTD---EAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEglPR-VLLPY 1181
Cdd:cd05044      3 LGSGAFGEVFEGTAKDilgDGSGETKVAVKTLRKGATDQEKAEFLKEAHLMSNFKHPNILKLLGVCLDND--PQyIILEL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSAQCPGWgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05044     81 MEGGDLLSYLRAARPTAFTPPLL---------------------TLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLV 139
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1262 DES----FTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05044    140 SSKdyreRVVKIGDFGLARDIYKNDYY--RKEGEGLLPVRWMAPESLVDGVFTTQSDV 195
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
1104-1315 3.85e-42

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: 156.07  E-value: 3.85e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMR 1183
Cdd:cd05043     12 DLLQEGTFGRIFHGILRDEKGKEEEVLVKTVKDHASEIQVTMLLQESSLLYGLSHQNLLPILHVCIEDGEKPMVLYPYMN 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQRVSAQCPgwgVSASTHlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05043     92 WGNLKLFLQQCRLSEANNP---QALSTQ-----------------QLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDD 151
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1264 SFTVKVADFGLARGILDKEYYSV--RQHRharlPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05043    152 ELQVKITDNALSRDLFPMDYHCLgdNENR----PIKWMSLESLVNKEYSSASDV 201
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
1106-1315 3.99e-42

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: 156.01  E-value: 3.99e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYT--DEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLppEGLPR-VLLPYM 1182
Cdd:cd05036     14 LGQGAFGEVYEGTVSgmPGDPSPLQVAVKTLPELCSEQDEMDFLMEALIMSKFNHPNIVRCIGVCF--QRLPRfILLELM 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRspqrvsaqcpgwgvsasthlcRCSPVSSCPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05036     92 AGGDLKSFLR---------------------ENRPRPEQPSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLT 150
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1263 ESFT---VKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05036    151 CKGPgrvAKIGDFGMARDIYRADYY--RKGGKAMLPVKWMPPEAFLDGIFTSKTDV 204
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
1093-1315 4.69e-42

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: 156.42  E-value: 4.69e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQVVihTDQVIGKGHFGVVYHGEY--TDEAQNQ-IHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGIm 1168
Cdd:cd05053      9 LPRDRLT--LGKPLGEGAFGQVVKAEAvgLDNKPNEvVTVAVKMLKDDATEKDLSDLVSEMEMMKMIgKHKNIINLLGA- 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1169 LPPEGLPRVLLPYMRHGDLLRFIRSPQRVSAQCpgwgvsasthlcrcSPVSSCP--QNPTVKDLISFGLQVACGMEYLAE 1246
Cdd:cd05053     86 CTQDGPLYVVVEYASKGNLREFLRARRPPGEEA--------------SPDDPRVpeEQLTQKDLVSFAYQVARGMEYLAS 151
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1247 QKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05053    152 KKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYY--RKTTNGRLPVKWMAPEALFDRVYTHQSDV 218
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
1100-1315 3.89e-41

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: 152.50  E-value: 3.89e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYtdeaQNQiHCAIKSLSRitEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLL 1179
Cdd:cd05039      8 LKLGELIGKGEFGDVMLGDY----RGQ-KVAVKCLKD--DSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGL-YIVT 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIRSPQRvsaqcpgwgvsasTHLcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd05039     80 EYMAKGSLVDYLRSRGR-------------AVI-------------TRKDQLGFALDVCEGMEYLESKKFVHRDLAARNV 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1260 MLDESFTVKVADFGLARgildkeyYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05039    134 LVSEDNVAKVSDFGLAK-------EASSNQDGGKLPIKWTAPEALREKKFSTKSDV 182
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
1106-1315 5.18e-41

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: 152.92  E-value: 5.18e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQ-IHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGL-PRVLLPYMR 1183
Cdd:cd05038     12 LGEGHFGSVELCRYDPLGDNTgEQVAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCESPGRRsLRLIMEYLP 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscPQNPTvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05038     92 SGSLRDYLQRHR--------------------------DQIDL-KRLLLFASQICKGMEYLGSQRYIHRDLAARNILVES 144
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1264 SFTVKVADFGLARGI-LDKEYYSVRQHRHarLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05038    145 EDLVKISDFGLAKVLpEDKEYYYVKEPGE--SPIFWYAPECLRESRFSSASDV 195
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
1106-1315 6.70e-41

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: 151.28  E-value: 6.70e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHCAIKSLSRITevQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd05034      3 LGAGQFGEVWMGVW----NGTTKVAVKTLKPGT--MSPEAFLQEAQIMKKLRHDKLVQLYAVCSDEEPI-YIVTELMSKG 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd05034     76 SLLDYLRTGE--------------------------GRALRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENN 129
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEYysvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05034    130 VCKVADFGLARLIEDDEY---TAREGAKFPIKWTAPEAALYGRFTIKSDV 176
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
1106-1315 3.94e-40

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: 150.75  E-value: 3.94e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYH----GEYTDEAQNQIhcAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLppEGLPRVLL-P 1180
Cdd:cd05050     13 IGQGAFGRVFQarapGLLPYEPFTMV--AVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCA--VGKPMCLLfE 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRspqrvsAQCPGWGVSASTHLCRCSpvsSCPQNP---TVKDLISFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd05050     89 YMAYGDLNEFLR------HRSPRAQCSLSHSTSSAR---KCGLNPlplSCTEQLCIAKQVAAGMAYLSERKFVHRDLATR 159
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1258 NCMLDESFTVKVADFGLARGILDKEYYSVRQHRHarLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05050    160 NCLVGENMVVKIADFGLSRNIYSADYYKASENDA--IPIRWMPPESIFYNRYTTESDV 215
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
1106-1315 3.95e-40

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: 149.42  E-value: 3.95e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPeglPRVLLPYM-RH 1184
Cdd:cd05060      3 LGHGNFGSVRKGVYLMKSGKEVEVAVKTLKQEHEKAGKKEFLREASVMAQLDHPCIVRLIGVCKGE---PLMLVMELaPL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd05060     80 GPLLKYLKKRREI----------------------------PVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNR 131
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1265 FTVKVADFGLARGI-LDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05060    132 HQAKISDFGMSRALgAGSDYYRATT--AGRWPLKWYAPECINYGKFSSKSDV 181
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
1100-1315 5.72e-39

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: 146.84  E-value: 5.72e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQ--IHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLppEGLPRV 1177
Cdd:cd05049      7 IVLKRELGEGAFGKVFLGECYNLEPEQdkMLVAVKTLKDASSPDARKDFEREAELLTNLQHENIVKFYGVCT--EGDPLL 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LL-PYMRHGDLLRFIRS--PQRVSAQCPGwgvSASTHLcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDL 1254
Cdd:cd05049     85 MVfEYMEHGDLNKFLRShgPDAAFLASED---SAPGEL-------------TLSQLLHIAVQIASGMVYLASQHFVHRDL 148
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1255 AARNCMLDESFTVKVADFGLARGILDKEYYSVRQHRhaRLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05049    149 ATRNCLVGTNLVVKIGDFGMSRDIYSTDYYRVGGHT--MLPIRWMPPESILYRKFTTESDV 207
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
1104-1315 6.29e-39

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: 146.79  E-value: 6.29e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQN-QIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPeglpRVLL--P 1180
Cdd:cd05057     13 KVLGSGAFGTVYKGVWIPEGEKvKIPVAIKVLREETGPKANEEILDEAYVMASVDHPHLVRLLGICLSS----QVQLitQ 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQ-RVSAQcpgwgvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd05057     89 LMPLGCLLDYVRNHRdNIGSQ----------------------------LLLNWCVQIAKGMSYLEEKRLVHRDLAARNV 140
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1260 MLDESFTVKVADFGLARgILD---KEYYSvrqhRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05057    141 LVKTPNHVKITDFGLAK-LLDvdeKEYHA----EGGKVPIKWMALESIQYRIYTHKSDV 194
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
1093-1315 4.83e-38

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: 144.73  E-value: 4.83e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQVVIHTDqvIGKGHFGVVYHGEYTD--EAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMlp 1170
Cdd:cd05061      3 VSREKITLLRE--LGQGSFGMVYEGNARDiiKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVV-- 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1171 PEGLPR-VLLPYMRHGDLLRFIRSPQRVSAQCPGwgvsasthlcrcSPVsscpqnPTVKDLISFGLQVACGMEYLAEQKF 1249
Cdd:cd05061     79 SKGQPTlVVMELMAHGDLKSYLRSLRPEAENNPG------------RPP------PTLQEMIQMAAEIADGMAYLNAKKF 140
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1250 VHRDLAARNCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05061    141 VHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYY--RKGGKGLLPVRWMAPESLKDGVFTTSSDM 204
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
1106-1315 3.48e-37

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: 140.75  E-value: 3.48e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIhCAIKSLSRITEVQEV-EAFLREGLIMRGLHHPNILALIGIML-PPEglPRVLLPYMR 1183
Cdd:cd13999      1 IGSGSFGEVYKGKW----RGTD-VAIKKLKVEDDNDELlKEFRREVSILSKLRHPNIVQFIGACLsPPP--LCIVTEYMP 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQRvsaqcpgwgvsasthlcrcspvsscpqNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd13999     74 GGSLYDLLHKKKI---------------------------PLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDE 126
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1264 SFTVKVADFGLAR------GILDKEYYSVRqhrharlpvkWMALESLQTYRFTTKSDV 1315
Cdd:cd13999    127 NFTVKIADFGLSRiknsttEKMTGVVGTPR----------WMAPEVLRGEPYTEKADV 174
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
1100-1315 9.31e-37

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: 139.86  E-value: 9.31e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYtdEAQNQIhCAIKSLSRitEVQEVEAFLREGLIMRGLHHPNILALIGIML--PPEglpRV 1177
Cdd:cd05052      8 ITMKHKLGGGQYGEVYEGVW--KKYNLT-VAVKTLKE--DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTrePPF---YI 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRSPQRVSAqcpgwgvsasthlcrcspvsscpqNPTVkdLISFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd05052     80 ITEFMPYGNLLDYLRECNREEL------------------------NAVV--LLYMATQIASAMEYLEKKNFIHRDLAAR 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1258 NCMLDESFTVKVADFGLARGILDKEYYSvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05052    134 NCLVGENHLVKVADFGLSRLMTGDTYTA---HAGAKFPIKWTAPESLAYNKFSIKSDV 188
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
1100-1315 1.58e-35

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: 136.78  E-value: 1.58e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIML-PPEGLPRVL 1178
Cdd:cd05056      8 ITLGRCIGEGQFGDVYQGVYMSPENEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITeNPVWIVMEL 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYmrhGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd05056     88 APL---GELRSYLQVNK---------------------------YSLDLASLILYAYQLSTALAYLESKRFVHRDIAARN 137
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLARGILDKEYYSVRQhrhARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05056    138 VLVSSPDCVKLGDFGLSRYMEDESYYKASK---GKLPIKWMAPESINFRRFTSASDV 191
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
1144-1315 6.27e-35

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: 135.93  E-value: 6.27e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1144 EAFLREGLIMRGLHHPNILALIGIMLPPEGLPrVLLPYMRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcsPVSSCPQ 1223
Cdd:cd05051     64 EDFLKEVKIMSQLKDPNIVRLLGVCTRDEPLC-MIVEYMENGDLNQFLQKHEAET------------------QGASATN 124
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1224 NPTV--KDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYSVRQhrHARLPVKWMAL 1301
Cdd:cd05051    125 SKTLsyGTLLYMATQIASGMKYLESLNFVHRDLATRNCLVGPNYTIKIADFGMSRNLYSGDYYRIEG--RAVLPIRWMAW 202
                          170
                   ....*....|....
gi 2678964124 1302 ESLQTYRFTTKSDV 1315
Cdd:cd05051    203 ESILLGKFTTKSDV 216
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
1103-1315 1.01e-34

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: 135.09  E-value: 1.01e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1103 DQVIGKGHFGVVYHGEYTDEA--QNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGiMLPPEGLPRVLLP 1180
Cdd:cd05045      5 GKTLGEGEFGKVVKATAFRLKgrAGYTTVAVKMLKENASSSELRDLLSEFNLLKQVNHPHVIKLYG-ACSQDGPLLLIVE 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVsaQCPGWGVSASTHlcrcspvSSCPQNP-----TVKDLISFGLQVACGMEYLAEQKFVHRDLA 1255
Cdd:cd05045     84 YAKYGSLRSFLRESRKV--GPSYLGSDGNRN-------SSYLDNPderalTMGDLISFAWQISRGMQYLAEMKLVHRDLA 154
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1256 ARNCMLDESFTVKVADFGLARGILDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05045    155 ARNVLVAEGRKMKISDFGLSRDVYEEDSYVKRS--KGRIPVKWMAIESLFDHIYTTQSDV 212
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
1106-1315 1.76e-34

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: 133.69  E-value: 1.76e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHCAIKSLSRITevQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd05068     16 LGSGQFGEVWEGLW----NNTTPVAVKTLKPGT--MDPEDFLREAQIMKKLRHPKLIQLYAVCTLEEPI-YIITELMKHG 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSPQRvsaqcpgwgvsaSTHLcrcspvsscPQnptvkdLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd05068     89 SLLEYLQGKGR------------SLQL---------PQ------LIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENN 141
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05068    142 ICKVADFGLARVIKVEDEYEARE--GAKFPIKWTAPEAANYNRFSIKSDV 189
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
1106-1315 8.53e-34

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: 131.40  E-value: 8.53e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHCAIKSLSRITEVQEVEaFLREGLIMRGLHHPNILALIGIMlpPEGLP-RVLLPYMRH 1184
Cdd:cd05148     14 LGSGYFGEVWEGLW----KNRVRVAIKILKSDDLLKQQD-FQKEVQALKRLRHKHLISLFAVC--SVGEPvYIITELMEK 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSPQRvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd05148     87 GSLLAFLRSPEG--------------------------QVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGED 140
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1265 FTVKVADFGLARgILDKEYYSVRQHrhaRLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05148    141 LVCKVADFGLAR-LIKEDVYLSSDK---KIPYKWTAPEAASHGTFSTKSDV 187
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
1106-1315 9.80e-34

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: 131.03  E-value: 9.80e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHCAIKSLSRITEVQevEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd05059     12 LGSGQFGVVHLGKW----RGKIDVAIKMIKEGSMSE--DDFIEEAKVMMKLSHPKLVQLYGVCTKQRPI-FIVTEYMANG 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRspqrvsaQCPGWGVSASthlcrcspvsscpqnptvkdLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd05059     85 CLLNYLR-------ERRGKFQTEQ--------------------LLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQN 137
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEYYSvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05059    138 VVKVSDFGLARYVLDDEYTS---SVGTKFPVKWSPPEVFMYSKFSSKSDV 184
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
1106-1315 5.20e-33

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: 129.00  E-value: 5.20e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQE--VEAFLREGLIMRGLHHPNILALIGIML-PPEGLPRVLLPYm 1182
Cdd:cd05040      3 LGDGSFGVVRRGEWTTPSGKVIQVAVKCLKSDVLSQPnaMDDFLKEVNAMHSLDHPNLIRLYGVVLsSPLMMVTELAPL- 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 rhGDLLRFIRSPQRvsaqcpgwgvsastHLcrcsPVSScpqnptvkdLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05040     82 --GSLLDRLRKDQG--------------HF----LIST---------LCDYAVQIANGMAYLESKRFIHRDLAARNILLA 132
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1263 ESFTVKVADFGLARGI-LDKEYYSVRQHRhaRLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05040    133 SKDKVKIGDFGLMRALpQNEDHYVMQEHR--KVPFAWCAPESLKTRKFSHASDV 184
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
1106-1315 7.00e-33

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: 129.32  E-value: 7.00e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTD--EAQNQIHCAIKSLSRITEVQEVEaFLREGLIMRGLHHPNILALIGIMlpPEGLPRVLL-PYM 1182
Cdd:cd05092     13 LGEGAFGKVFLAECHNllPEQDKMLVAVKALKEATESARQD-FQREAELLTVLQHQHIVRFYGVC--TEGEPLIMVfEYM 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSpqrvsaQCPGWGVSASTHLCRCSPVsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05092     90 RHGDLNRFLRS------HGPDAKILDGGEGQAPGQL-------TLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVG 156
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1263 ESFTVKVADFGLARGILDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05092    157 QGLVVKIGDFGMSRDIYSTDYYRVGG--RTMLPIRWMPPESILYRKFTTESDI 207
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
1104-1315 9.66e-33

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: 129.53  E-value: 9.66e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEY--TDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGIMLPPEGLPRVLLP 1180
Cdd:cd05054     13 KPLGRGAFGKVIQASAfgIDKSATCRTVAVKMLKEGATASEHKALMTELKILIHIgHHLNVVNLLGACTKPGGPLMVIVE 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVSAQCPGWGVSASTHLCRCSPVSSCPQnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05054     93 FCKFGNLSNYLRSKREEFVPYRDKGARDVEEEEDDDELYKEPL--TLEDLICYSFQVARGMEFLASRKCIHRDLAARNIL 170
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1261 LDESFTVKVADFGLARGIL-DKEYysVRQHrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05054    171 LSENNVVKICDFGLARDIYkDPDY--VRKG-DARLPLKWMAPESIFDKVYTTQSDV 223
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
1105-1315 1.61e-32

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: 127.97  E-value: 1.61e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEY--TDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGimLPPEGLPR-VLLPY 1181
Cdd:cd05046     12 TLGRGEFGEVFLAKAkgIEEEGGETLVLVKALQKTKDENLQSEFRRELDMFRKLSHKNVVRLLG--LCREAEPHyMILEY 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSAqcpgwgvsasthlcrcspvSSCPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05046     90 TDLGDLKQFLRATKSKDE-------------------KLKPPPLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLV 150
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1262 DESFTVKVADFGLARGILDKEYYsvrQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05046    151 SSQREVKVSLLSLSKDVYNSEYY---KLRNALIPLRWLAPEAVQEDDFSTKSDV 201
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
1105-1315 5.39e-32

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: 126.31  E-value: 5.39e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEAqNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGiMLPPEGLPRVLLPYMR 1183
Cdd:cd05047      2 VIGEGNFGQVLKARIKKDG-LRMDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLG-ACEHRGYLYLAIEYAP 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSpQRVSAQCPGWGVSASThlcrCSPVSScpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05047     80 HGNLLDFLRK-SRVLETDPAFAIANST----ASTLSS-------QQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGE 147
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1264 SFTVKVADFGLARGildKEYYSvrQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05047    148 NYVAKIADFGLSRG---QEVYV--KKTMGRLPVRWMAIESLNYSVYTTNSDV 194
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
1106-1315 5.45e-32

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: 127.40  E-value: 5.45e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVV----------YHGEYTDEAQNQ-IHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGL 1174
Cdd:cd05097     13 LGEGQFGEVhlceaeglaeFLGEGAPEFDGQpVLVAVKMLRADVTKTARNDFLKEIKIMSRLKNPNIIRLLGVCVSDDPL 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1175 PRVLlPYMRHGDLLRFIrSPQRVSAQCpgwgvsasTHLCRCSPVSscpqnptVKDLISFGLQVACGMEYLAEQKFVHRDL 1254
Cdd:cd05097     93 CMIT-EYMENGDLNQFL-SQREIESTF--------THANNIPSVS-------IANLLYMAVQIASGMKYLASLNFVHRDL 155
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1255 AARNCMLDESFTVKVADFGLARGILDKEYYSVrQHRhARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05097    156 ATRNCLVGNHYTIKIADFGMSRNLYSGDYYRI-QGR-AVLPIRWMAWESILLGKFTTASDV 214
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
1104-1315 6.78e-32

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: 125.76  E-value: 6.78e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDE--AQNQIHCAIKSlsritevqevEAFLREGLIMRGLHHPNILALIGIMLPpEGLpRVLLPY 1181
Cdd:cd05083     12 EIIGEGEFGAVLQGEYMGQkvAVKNIKCDVTA----------QAFLEETAVMTKLQHKNLVRLLGVILH-NGL-YIVMEL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSAQCPgwgvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05083     80 MSKGNLVNFLRSRGRALVPVI--------------------------QLLQFSLDVAEGMEYLESKKLVHRDLAARNILV 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1262 DESFTVKVADFGLARgildkeyYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05083    134 SEDGVAKISDFGLAK-------VGSMGVDNSRLPVKWTAPEALKNKKFSSKSDV 180
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
1104-1315 7.52e-32

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: 125.25  E-value: 7.52e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEaqnQIHCAIKSlSRITEVQEVEA-FLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYM 1182
Cdd:cd05041      1 EKIGRGNFGDVYRGVLKPD---NTEVAVKT-CRETLPPDLKRkFLQEARILKQYDHPNIVKLIGVCVQKQPI-MIVMELV 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPqrvSAQCPgwgvsasthlcrcspvsscpqnptVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05041     76 PGGSLLTFLRKK---GARLT------------------------VKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVG 128
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1263 ESFTVKVADFGLARGILDKEYYSVRQHRhaRLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05041    129 ENNVLKISDFGMSREEEDGEYTVSDGLK--QIPIKWTAPEALNYGRYTSESDV 179
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
1104-1315 1.01e-31

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 124.95  E-value: 1.01e-31
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  1104 QVIGKGHFGVVYHGEYTDEAQnqiHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMR 1183
Cdd:smart00220    5 EKLGEGSFGKVYLARDKKTGK---LVAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVM-EYCE 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  1184 HGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:smart00220   81 GGDLFDLLKKRGRLS----------------------------EDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDE 132
                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124  1264 SFTVKVADFGLARGILDKEYYSVRQH-RHarlpvkWMALESLQTYRFTTKSDV 1315
Cdd:smart00220  133 DGHVKLADFGLARQLDPGEKLTTFVGtPE------YMAPEVLLGKGYGKAVDI 179
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
1093-1315 1.01e-31

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: 125.92  E-value: 1.01e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQVVIHTDqvIGKGHFGVVYHG----EYTDEAQNQIhcAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIM 1168
Cdd:cd05062      3 VAREKITMSRE--LGQGSFGMVYEGiakgVVKDEPETRV--AIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVV 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1169 lpPEGLPR-VLLPYMRHGDLLRFIRSPQRVSAQCPGWGVsasthlcrcspvsscpqnPTVKDLISFGLQVACGMEYLAEQ 1247
Cdd:cd05062     79 --SQGQPTlVIMELMTRGDLKSYLRSLRPEMENNPVQAP------------------PSLKKMIQMAGEIADGMAYLNAN 138
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1248 KFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05062    139 KFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYY--RKGGKGLLPVRWMSPESLKDGVFTTYSDV 204
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
1146-1315 5.19e-31

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: 124.66  E-value: 5.19e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1146 FLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMRHGDLLRFIRSPQRVSAQCPGWGVSASTHlcrCSPVSSCPQnp 1225
Cdd:cd05096     66 FLKEVKILSRLKDPNIIRLLGVCVDEDPLCMIT-EYMENGDLNQFLSSHHLDDKEENGNDAVPPAH---CLPAISYSS-- 139
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1226 tvkdLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYSVrQHRhARLPVKWMALESLQ 1305
Cdd:cd05096    140 ----LLHVALQIASGMKYLSSLNFVHRDLATRNCLVGENLTIKIADFGMSRNLYAGDYYRI-QGR-AVLPIRWMAWECIL 213
                          170
                   ....*....|
gi 2678964124 1306 TYRFTTKSDV 1315
Cdd:cd05096    214 MGKFTTASDV 223
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
1106-1315 7.83e-31

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: 121.22  E-value: 7.83e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQnqiHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLppEGLPRVL-LPYMRH 1184
Cdd:cd00180      1 LGKGSFGKVYKARDKETGK---KVAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFE--TENFLYLvMEYCEG 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSpqrvsaqcpgwgvsasthlcrcspvssCPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd00180     76 GSLKDLLKE---------------------------NKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSD 128
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1265 FTVKVADFGLARGILDKEYYSVRQHRHarLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd00180    129 GTVKLADFGLAKDLDSDDSLLKTTGGT--TPPYYAPPELLGGRYYGPKVDI 177
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
1100-1315 1.60e-30

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: 122.10  E-value: 1.60e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQIHCAIKSL-SRITEVQEVEaFLREGLIMRGLHHPNILALIGIMLPPEGLpRVL 1178
Cdd:cd05033      6 VTIEKVIGGGEFGEVCSGSLKLPGKKEIDVAIKTLkSGYSDKQRLD-FLTEASIMGQFDHPNVIRLEGVVTKSRPV-MIV 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMRHGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd05033     84 TEYMENGSLDKFLREND---------------------------GKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARN 136
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLARGILDKEyySVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05033    137 ILVNSDLVCKVSDFGLSRRLEDSE--ATYTTKGGKIPIRWTAPEAIAYRKFTSASDV 191
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
1104-1315 6.23e-30

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: 121.44  E-value: 6.23e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEY--TDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGiMLPPEGLPRVLLP 1180
Cdd:cd05055     41 KTLGAGAFGKVVEATAygLSKSDAVMKVAVKMLKPTAHSSEREALMSELKIMSHLgNHENIVNLLG-ACTIGGPILVITE 119
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVSAqcpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05055    120 YCCYGDLLNFLRRKRESFL--------------------------TLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVL 173
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1261 LDESFTVKVADFGLARGILDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05055    174 LTHGKIVKICDFGLARDIMNDSNYVVKG--NARLPVKWMAPESIFNCVYTFESDV 226
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
1104-1315 9.98e-30

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: 119.32  E-value: 9.98e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYtdeaqNQIHCAIKSLSRITEVQeveAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMR 1183
Cdd:cd05082     12 QTIGKGEFGDVMLGDY-----RGNKVAVKCIKNDATAQ---AFLAEASVMTQLRHSNLVQLLGVIVEEKGGLYIVTEYMA 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQR--VSAQCpgwgvsasthlcrcspvsscpqnptvkdLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05082     84 KGSLVDYLRSRGRsvLGGDC----------------------------LLKFSLDVCEAMEYLEGNNFVHRDLAARNVLV 135
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1262 DESFTVKVADFGLArgildKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05082    136 SEDNVAKVSDFGLT-----KEASSTQD--TGKLPVKWTAPEALREKKFSTKSDV 182
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
1100-1315 1.37e-29

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: 120.10  E-value: 1.37e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAqNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGiMLPPEGLPRVL 1178
Cdd:cd05089      4 IKFEDVIGEGNFGQVIKAMIKKDG-LKMNAAIKMLKEFASENDHRDFAGELEVLCKLgHHPNIINLLG-ACENRGYLYIA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMRHGDLLRFIRSpQRVSAQCPGWGVSASThlcrCSPVSScpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd05089     82 IEYAPYGNLLDFLRK-SRVLETDPAFAKEHGT----ASTLTS-------QQLLQFASDVAKGMQYLSEKQFIHRDLAARN 149
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLARGildKEYYSvrQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05089    150 VLVGENLVSKIADFGLSRG---EEVYV--KKTMGRLPVRWMAIESLNYSVYTTKSDV 201
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
1106-1315 1.64e-29

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: 119.76  E-value: 1.64e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEA--QNQIHCAIKSLSRITEVQEVEaFLREGLIMRGLHHPNILALIGIMLppEGLPRVLL-PYM 1182
Cdd:cd05093     13 LGEGAFGKVFLAECYNLCpeQDKILVAVKTLKDASDNARKD-FHREAELLTNLQHEHIVKFYGVCV--EGDPLIMVfEYM 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRspqrvsAQCPGWGVSASthlcrcspvSSCPQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05093     90 KHGDLNKFLR------AHGPDAVLMAE---------GNRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVG 154
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1263 ESFTVKVADFGLARGILDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05093    155 ENLLVKIGDFGMSRDVYSTDYYRVGG--HTMLPIRWMPPESIMYRKFTTESDV 205
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
1100-1315 2.89e-29

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: 118.13  E-value: 2.89e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQV-----IGKGHFGVVYHGEYtdeaQNQIHCAIKSLsRITEVQEvEAFLREGLIMRGLHHPNILALIGIMLppEGL 1174
Cdd:cd05112      1 IDPSELtfvqeIGSGQFGLVHLGYW----LNKDKVAIKTI-REGAMSE-EDFIEEAEVMMKLSHPKLVQLYGVCL--EQA 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1175 PRVLL-PYMRHGDLLRFIRSpQRVSaqcpgwgVSASTHLCRCspvsscpqnptvkdlisfgLQVACGMEYLAEQKFVHRD 1253
Cdd:cd05112     73 PICLVfEFMEHGCLSDYLRT-QRGL-------FSAETLLGMC-------------------LDVCEGMAYLEEASVIHRD 125
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1254 LAARNCMLDESFTVKVADFGLARGILDKEYYSvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05112    126 LAARNCLVGENQVVKVSDFGMTRFVLDDQYTS---STGTKFPVKWSSPEVFSFSRYSSKSDV 184
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
1094-1315 3.75e-29

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: 119.30  E-value: 3.75e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1094 PHEQVVIhtDQVIGKGHFGVVYHGE-YTDEAQNQIH---CAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGIm 1168
Cdd:cd05099     10 PRDRLVL--GKPLGEGCFGQVVRAEaYGIDKSRPDQtvtVAVKMLKDNATDKDLADLISEMELMKLIgKHKNIINLLGV- 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1169 LPPEGLPRVLLPYMRHGDLLRFIRSPQRvsaqcPGWGVSASthlcrcspVSSCPQNP-TVKDLISFGLQVACGMEYLAEQ 1247
Cdd:cd05099     87 CTQEGPLYVIVEYAAKGNLREFLRARRP-----PGPDYTFD--------ITKVPEEQlSFKDLVSCAYQVARGMEYLESR 153
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1248 KFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05099    154 RCIHRDLAARNVLVTEDNVMKIADFGLARGVHDIDYY--KKTSNGRLPVKWMAPEALFDRVYTHQSDV 219
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
1106-1315 6.63e-29

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: 117.81  E-value: 6.63e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEY----TDEAQnqiHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPrVLLPY 1181
Cdd:cd05090     13 LGECAFGKIYKGHLylpgMDHAQ---LVAIKTLKDYNNPQQWNEFQQEASLMTELHHPNIVCLLGVVTQEQPVC-MLFEF 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFI--RSPQRvSAQCpgwgvsasthlcrcspvsSCPQNPTVK------DLISFGLQVACGMEYLAEQKFVHRD 1253
Cdd:cd05090     89 MNQGDLHEFLimRSPHS-DVGC------------------SSDEDGTVKssldhgDFLHIAIQIAAGMEYLSSHFFVHKD 149
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1254 LAARNCMLDESFTVKVADFGLARGILDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05090    150 LAARNILVGEQLHVKISDLGLSREIYSSDYYRVQN--KSLLPIRWMPPEAIMYGKFSSDSDI 209
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
1106-1315 1.17e-28

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: 117.40  E-value: 1.17e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGE------YTDE------AQNQ-IHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPE 1172
Cdd:cd05095     13 LGEGQFGEVHLCEaegmekFMDKdfalevSENQpVLVAVKMLRADANKNARNDFLKEIKIMSRLKDPNIIRLLAVCITDD 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 GLPrVLLPYMRHGDLLRFIrspQRVSAQCPGWGVSASthlcrcSPVSscpqnptVKDLISFGLQVACGMEYLAEQKFVHR 1252
Cdd:cd05095     93 PLC-MITEYMENGDLNQFL---SRQQPEGQLALPSNA------LTVS-------YSDLRFMAAQIASGMKYLSSLNFVHR 155
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLARGILDKEYYSVrQHRhARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05095    156 DLATRNCLVGKNYTIKIADFGMSRNLYSGDYYRI-QGR-AVLPIRWMSWESILLGKFTTASDV 216
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
1106-1315 1.50e-28

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: 116.13  E-value: 1.50e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHCAIKSLsRITEVQEVEaFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd05113     12 LGTGQFGVVKYGKW----RGQYDVAIKMI-KEGSMSEDE-FIEEAKVMMNLSHEKLVQLYGVCTKQRPI-FIITEYMANG 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSPQRvsaqcpgwgvsasthlcrcspvsscpqNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd05113     85 CLLNYLREMRK---------------------------RFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQG 137
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEYYSvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05113    138 VVKVSDFGLSRYVLDDEYTS---SVGSKFPVRWSPPEVLMYSKFSSKSDV 184
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
1093-1315 1.69e-28

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: 116.29  E-value: 1.69e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQvvIHTDQVIGKGHFGVVYHGEYtdeaQNQIHCAIKSLSRITevQEVEAFLREGLIMRGLHHPNILALIGIMLPPE 1172
Cdd:cd05072      4 IPRES--IKLVKKLGAGQFGEVWMGYY----NNSTKVAVKTLKPGT--MSVQAFLEEANLMKTLQHDKLVRLYAVVTKEE 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 GLpRVLLPYMRHGDLLRFIRSPQRVSAQCPgwgvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHR 1252
Cdd:cd05072     76 PI-YIITEYMAKGSLLDFLKSDEGGKVLLP--------------------------KLIDFSAQIAEGMAYIERKNYIHR 128
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLARGILDKEyYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05072    129 DLRAANVLVSESLMCKIADFGLARVIEDNE-YTARE--GAKFPIKWTAPEAINFGSFTIKSDV 188
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
1104-1315 2.60e-28

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: 115.89  E-value: 2.60e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQN-QIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPE-GLPRVLLPY 1181
Cdd:cd05109     13 KVLGSGAFGTVYKGIWIPDGENvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLTSTvQLVTQLMPY 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 mrhGDLLRFIRSPQ-RVSAQcpgwgvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05109     93 ---GCLLDYVRENKdRIGSQ----------------------------DLLNWCVQIAKGMSYLEEVRLVHRDLAARNVL 141
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1261 LDESFTVKVADFGLAR--GILDKEYYSvrqhRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05109    142 VKSPNHVKITDFGLARllDIDETEYHA----DGGKVPIKWMALESILHRRFTHQSDV 194
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
1081-1315 4.69e-28

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: 116.27  E-value: 4.69e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1081 DKMLLAEVKDVLIPHE------QVVIHTDQVIGKGHFGVVYHGEY----TDEAQNQIHCAIKSLSRITEVQEVEAFLREG 1150
Cdd:cd05101      1 DAPMLAGVSEYELPEDpkwefpRDKLTLGKPLGEGCFGQVVMAEAvgidKDKPKEAVTVAVKMLKDDATEKDLSDLVSEM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1151 LIMRGL-HHPNILALIGiMLPPEGLPRVLLPYMRHGDLLRFIRSPQRvsaqcPGWGVSASthlcrcspVSSCPQNP-TVK 1228
Cdd:cd05101     81 EMMKMIgKHKNIINLLG-ACTQDGPLYVIVEYASKGNLREYLRARRP-----PGMEYSYD--------INRVPEEQmTFK 146
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1229 DLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYR 1308
Cdd:cd05101    147 DLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYY--KKTTNGRLPVKWMAPEALFDRV 224

                   ....*..
gi 2678964124 1309 FTTKSDV 1315
Cdd:cd05101    225 YTHQSDV 231
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
1093-1315 5.31e-28

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: 116.62  E-value: 5.31e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQvvIHTDQVIGKGHFGVVYHGEY--TDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGIML 1169
Cdd:cd05102      4 FPRDR--LRLGKVLGHGAFGKVVEASAfgIDKSSSCETVAVKMLKEGATASEHKALMSELKILIHIgNHLNVVNLLGACT 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1170 PPEGLPRVLLPYMRHGDLLRFIR------------SPQ---------------RVSAQCPGWGVSASTHLCRCSP----V 1218
Cdd:cd05102     82 KPNGPLMVIVEFCKYGNLSNFLRakregfspyrerSPRtrsqvrsmveavradRRSRQGSDRVASFTESTSSTNQprqeV 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1219 SSCPQNP-TVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGIL-DKEYysVRQHrHARLPV 1296
Cdd:cd05102    162 DDLWQSPlTMEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYkDPDY--VRKG-SARLPL 238
                          250
                   ....*....|....*....
gi 2678964124 1297 KWMALESLQTYRFTTKSDV 1315
Cdd:cd05102    239 KWMAPESIFDKVYTTQSDV 257
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
1103-1315 6.88e-28

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: 115.89  E-value: 6.88e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1103 DQVIGKGHFGVVYHGEYTDEAQN-QIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPE-GLPRVLLP 1180
Cdd:cd05108     12 IKVLGSGAFGTVYKGLWIPEGEKvKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTvQLITQLMP 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YmrhGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05108     92 F---GCLLDYVREHK---------------------------DNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVL 141
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1261 LDESFTVKVADFGLAR--GILDKEYysvrQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05108    142 VKTPQHVKITDFGLAKllGAEEKEY----HAEGGKVPIKWMALESILHRIYTHQSDV 194
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
1104-1315 1.16e-27

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: 116.48  E-value: 1.16e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgEYT----DEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGIMlpPEGLP-RV 1177
Cdd:cd05106     44 KTLGAGAFGKVV--EATafglGKEDNVLRVAVKMLKASAHTDEREALMSELKILSHLgQHKNIVNLLGAC--THGGPvLV 119
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRF----------------------------------IRSPQRVSAQC----------PGWGVSASTHLC 1213
Cdd:cd05106    120 ITEYCCYGDLLNFlrkkaetflnfvmalpeisetssdyknitlekkyIRSDSGFSSQGsdtyvemrpvSSSSSQSSDSKD 199
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1214 RCSPVSSCPQNptVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYSVRQhrHAR 1293
Cdd:cd05106    200 EEDTEDSWPLD--LDDLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARDIMNDSNYVVKG--NAR 275
                          250       260
                   ....*....|....*....|..
gi 2678964124 1294 LPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05106    276 LPVKWMAPESIFDCVYTVQSDV 297
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
1106-1315 1.90e-27

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: 113.57  E-value: 1.90e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEA---QNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYM 1182
Cdd:cd05091     14 LGEDRFGKVYKGHLFGTApgeQTQA-VAIKTLKDKAEGPLREEFRHEAMLRSRLQHPNIVCLLGVVTKEQPM-SMIFSYC 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFI--RSPQrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVK------DLISFGLQVACGMEYLAEQKFVHRDL 1254
Cdd:cd05091     92 SHGDLHEFLvmRSPH--------------------SDVGSTDDDKTVKstlepaDFLHIVTQIAAGMEYLSSHHVVHKDL 151
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1255 AARNCMLDESFTVKVADFGLARGILDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05091    152 ATRNVLVFDKLNVKISDLGLFREVYAADYYKLMG--NSLLPIRWMSPEAIMYGKFSIDSDI 210
IPT_plexin_repeat2 cd01179
Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are ...
710-794 2.76e-27

Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present preceeded by SEMA (semaphorin) and PSI (plexin, semaphorin, integrin) domains.


Pssm-ID: 238584  Cd Length: 85  Bit Score: 106.54  E-value: 2.76e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  710 PMLTSIKPDFGPRAGGTYLTLEGQSLSVGTSRAVLVNGTQCRLEQVSEEKILCVTPPGAGTASVPLRLQIGGAEVRGSRT 789
Cdd:cd01179      1 PSITSLSPSYGPQSGGTRLTITGKHLNAGSSVRVTVGGQPCKILSVSSSQIVCLTPPSASPGEAPVKVLIDGARRLAPLV 80

                   ....*
gi 2678964124  790 FHYKE 794
Cdd:cd01179     81 FTYTE 85
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
1106-1315 3.42e-27

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: 112.29  E-value: 3.42e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHCAIKSLSRITevQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLprVLLPYMRHG 1185
Cdd:cd05067     15 LGAGQFGEVWMGYY----NGHTKVAIKSLKQGS--MSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIY--IITEYMENG 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSPQRVSAqcpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd05067     87 SLVDFLKTPSGIKL--------------------------TINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTL 140
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEYYSvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05067    141 SCKIADFGLARLIEDNEYTA---REGAKFPIKWTAPEAINYGTFTIKSDV 187
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
1100-1315 6.28e-27

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: 112.78  E-value: 6.28e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQnQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGiMLPPEGLPRVL 1178
Cdd:cd05088      9 IKFQDVIGEGNFGQVLKARIKKDGL-RMDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLG-ACEHRGYLYLA 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMRHGDLLRFIRSpQRVSAQCPGWGVSASThlcrCSPVSScpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd05088     87 IEYAPHGNLLDFLRK-SRVLETDPAFAIANST----ASTLSS-------QQLLHFAADVARGMDYLSQKQFIHRDLAARN 154
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLARGildKEYYSvrQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05088    155 ILVGENYVAKIADFGLSRG---QEVYV--KKTMGRLPVRWMAIESLNYSVYTTNSDV 206
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
1106-1315 6.41e-27

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: 111.49  E-value: 6.41e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHCAIKSLsRITEVQEvEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd05114     12 LGSGLFGVVRLGKW----RAQYKVAIKAI-REGAMSE-EDFIEEAKVMMKLTHPKLVQLYGVCTQQKPI-YIVTEFMENG 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSPQrvsaqcpgwgvsasTHLCRCSPVSSCpqnptvkdlisfgLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd05114     85 CLLNYLRQRR--------------GKLSRDMLLSMC-------------QDVCEGMEYLERNNFIHRDLAARNCLVNDTG 137
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEYYSvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05114    138 VVKVSDFGMTRYVLDDQYTS---SSGAKFPVKWSPPEVFNYSKFSSKSDV 184
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
1106-1315 7.32e-27

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: 113.19  E-value: 7.32e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYT----DEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGiMLPPEGLPRVLLP 1180
Cdd:cd05100     20 LGEGCFGQVVMAEAIgidkDKPNKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIgKHKNIINLLG-ACTQDGPLYVLVE 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRvsaqcPGWGVSASThlCRCSPvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05100     99 YASKGNLREYLRARRP-----PGMDYSFDT--CKLPE-----EQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVL 166
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1261 LDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05100    167 VTEDNVMKIADFGLARDVHNIDYY--KKTTNGRLPVKWMAPEALFDRVYTHQSDV 219
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
1104-1315 1.31e-26

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: 110.41  E-value: 1.31e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYtdEAQNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMR 1183
Cdd:cd05084      2 ERIGRGNFGEVFSGRL--RADNTP-VAVKSCRETLPPDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPI-YIVMELVQ 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSpqrvsaqcpgwgvsASTHLcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05084     78 GGDFLTFLRT--------------EGPRL-------------KVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTE 130
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1264 SFTVKVADFGLARGILDKEYYSVRQHRhaRLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05084    131 KNVLKISDFGMSREEEDGVYAATGGMK--QIPVKWTAPEALNYGRYSSESDV 180
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
1100-1315 2.36e-26

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: 109.96  E-value: 2.36e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSR-ITEVQEVEaFLREGLIMRGLHHPNILALIGIMlpPEGLP-RV 1177
Cdd:cd05066      6 IKIEKVIGAGEFGEVCSGRLKLPGKREIPVAIKTLKAgYTEKQRRD-FLSEASIMGQFDHPNIIHLEGVV--TRSKPvMI 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRspqRVSAQCpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd05066     83 VTEYMENGSLDAFLR---KHDGQF------------------------TVIQLVGMLRGIASGMKYLSDMGYVHRDLAAR 135
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1258 NCMLDESFTVKVADFGLARgILDKEYYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05066    136 NILVNSNLVCKVSDFGLSR-VLEDDPEAAYTTRGGKIPIRWTAPEAIAYRKFTSASDV 192
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
1106-1315 2.47e-26

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: 110.87  E-value: 2.47e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGE---YTDEAQNQI-HCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGiMLPPEGLPRVLLP 1180
Cdd:cd05098     21 LGEGCFGQVVLAEaigLDKDKPNRVtKVAVKMLKSDATEKDLSDLISEMEMMKMIgKHKNIINLLG-ACTQDGPLYVIVE 99
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSpqrvsAQCPGWGVSASThlcRCSPVsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05098    100 YASKGNLREYLQA-----RRPPGMEYCYNP---SHNPE----EQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVL 167
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1261 LDESFTVKVADFGLARGILDKEYYsvRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05098    168 VTEDNVMKIADFGLARDIHHIDYY--KKTTNGRLPVKWMAPEALFDRIYTHQSDV 220
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
1104-1315 2.50e-26

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: 110.93  E-value: 2.50e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQN-QIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEglPRVLLPYM 1182
Cdd:cd05110     13 KVLGSGAFGTVYKGIWVPEGETvKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPT--IQLVTQLM 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05110     91 PHGCLLDYVHEHK---------------------------DNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVK 143
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1263 ESFTVKVADFGLARGIL--DKEYYSvrqhRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05110    144 SPNHVKITDFGLARLLEgdEKEYNA----DGGKMPIKWMALECIHYRKFTHQSDV 194
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
1106-1315 1.08e-25

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: 110.07  E-value: 1.08e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEY--TDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGIMLPPEGLPRVLLPYM 1182
Cdd:cd05103     15 LGRGAFGQVIEADAfgIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGGPLMVIVEFC 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQ-----------RVSAQCPGWG-----------------VSASTHLCRCSPVSS-----------CPQ 1223
Cdd:cd05103     95 KFGNLSAYLRSKRsefvpyktkgaRFRQGKDYVGdisvdlkrrldsitssqSSASSGFVEEKSLSDveeeeagqedlYKD 174
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1224 NPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGIL-DKEYysVRQHrHARLPVKWMALE 1302
Cdd:cd05103    175 FLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYkDPDY--VRKG-DARLPLKWMAPE 251
                          250
                   ....*....|...
gi 2678964124 1303 SLQTYRFTTKSDV 1315
Cdd:cd05103    252 TIFDRVYTIQSDV 264
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
1106-1315 1.78e-25

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: 108.17  E-value: 1.78e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTD--EAQNQIHCAIKSLSRITeVQEVEAFLREGLIMRGLHHPNILALIGIMLppEGLPRVLL-PYM 1182
Cdd:cd05094     13 LGEGAFGKVFLAECYNlsPTKDKMLVAVKTLKDPT-LAARKDFQREAELLTNLQHDHIVKFYGVCG--DGDPLIMVfEYM 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRspqrvsAQCPGWGVsasthLCRCSPVSSCPQnPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05094     90 KHGDLNKFLR------AHGPDAMI-----LVDGQPRQAKGE-LGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVG 157
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1263 ESFTVKVADFGLARGILDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05094    158 ANLLVKIGDFGMSRDVYSTDYYRVGG--HTMLPIRWMPPESIMYRKFTTESDV 208
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
1104-1315 2.09e-25

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: 107.73  E-value: 2.09e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQN-QIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMlpPEGLPRVLLPYM 1182
Cdd:cd05111     13 KVLGSGVFGTVHKGIWIPEGDSiKIPVAIKVIQDRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGIC--PGASLQLVTQLL 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIR------SPQRvsaqcpgwgvsasthlcrcspvsscpqnptvkdLISFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd05111     91 PLGSLLDHVRqhrgslGPQL---------------------------------LLNWCVQIAKGMYYLEEHRMVHRNLAA 137
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1257 RNCMLDESFTVKVADFGLARGIL--DKEYYsvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05111    138 RNVLLKSPSQVQVADFGVADLLYpdDKKYF----YSEAKTPIKWMALESIHFGKYTHQSDV 194
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
1104-1315 2.15e-25

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: 106.63  E-value: 2.15e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQeveaFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMR 1183
Cdd:cd05085      2 ELLGKGNFGEVYKGTLKDKTPVAVKTCKEDLPQELKIK----FLSEARILKQYDHPNIVKLIGVCTQRQPI-YIVMELVP 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05085     77 GGDFLSFLRKKK---------------------------DELKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGE 129
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1264 SFTVKVADFGLARGILDKEYYS--VRQhrharLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05085    130 NNALKISDFGMSRQEDDGVYSSsgLKQ-----IPIKWTAPEALNYGRYSSESDV 178
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
1100-1315 3.07e-25

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: 106.88  E-value: 3.07e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQIHCAIKSL-SRITEVQEVEaFLREGLIMRGLHHPNILALIGIMlpPEGLPRVL 1178
Cdd:cd05065      6 VKIEEVIGAGEFGEVCRGRLKLPGKREIFVAIKTLkSGYTEKQRRD-FLSEASIMGQFDHPNIIHLEGVV--TKSRPVMI 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LP-YMRHGDLLRFIRspqrvsaqcpgwgvsasthlcrcspvsscpQNP---TVKDLISFGLQVACGMEYLAEQKFVHRDL 1254
Cdd:cd05065     83 ITeFMENGALDSFLR------------------------------QNDgqfTVIQLVGMLRGIAAGMKYLSEMNYVHRDL 132
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1255 AARNCMLDESFTVKVADFGLAR----GILDKEYYSVRQhrhARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05065    133 AARNILVNSNLVCKVSDFGLSRfledDTSDPTYTSSLG---GKIPIRWTAPEAIAYRKFTSASDV 194
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
1106-1315 1.10e-24

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: 104.61  E-value: 1.10e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQnqihCAIKSLSRITevQEVEAFLREGLIMRGLHHPNILALIGIMlpPEGLPRVLLPYMRHG 1185
Cdd:cd14203      3 LGQGCFGEVWMGTWNGTTK----VAIKTLKPGT--MSPEAFLEEAQIMKKLRHDKLVQLYAVV--SEEPIYIVTEFMSKG 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSPQRVSAQCPgwgvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd14203     75 SLLDFLKDGEGKYLKLP--------------------------QLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNL 128
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEyYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14203    129 VCKIADFGLARLIEDNE-YTARQ--GAKFPIKWTAPEAALYGRFTIKSDV 175
Sema_plexin_A2 cd11272
The Sema domain, a protein interacting module, of Plexin A2; Plexin A2 serves as a receptor ...
70-589 2.51e-24

The Sema domain, a protein interacting module, of Plexin A2; Plexin A2 serves as a receptor for class 6 semaphorins. Interactions between Plexin A2, A4 and semaphorins 6A and 6B control the lamina-restricted projection of hippocampal mossy fibers. Sema6B also repels the growth of mossy fibers in a Plexin A4 dependent manner. Plexin A2 does not suppress Sema6B function. In addition, studies have shown that Plexin A2 may be related to anxiety and other psychiatric disorders. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200533 [Multi-domain]  Cd Length: 515  Bit Score: 108.87  E-value: 2.51e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   70 AVFVAIRNRLHVLGPDLQYIESLTTGPIGDPgcqtcASCGP----GPHGPP----NDTDTLvLVMEPGLPALVSCGSTLQ 141
Cdd:cd11272     24 AVYVGAINRVYKLSGNLTILVAHKTGPEEDN-----KSCYPplivQPCSEVltltNNVNKL-LIIDYSENRLLACGSLYQ 97
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  142 GRCFLHEL-------EPQGEALHlaapaclFSASNNKPEACTDCVAS--------HLGTRVtvveQGHASYFYVASS--- 203
Cdd:cd11272     98 GVCKLLRLddlfilvEPSHKKEH-------YLSSVNKTGTMYGVIVRsegedgklFIGTAV----DGKQDYFPTLSSrkl 166
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  204 ---------LDPELAASFSPrsvSIRRLKSDTSGFQPGFPslsvlpkylasylIKYVHSFHSGDFVYFLTVQP-----MD 269
Cdd:cd11272    167 prdpessamLDYELHSDFVS---SLIKIPSDTLALVSHFD-------------IFYIYGFASGNFVYFLTVQPetpegVS 230
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  270 VRSPPSALQT-RLVRLNAIEPEIGDYRELVLDChfapkrrrrsgaPKSLQAYQVLQAAHSAPVDAKLALDLSISEGQEVL 348
Cdd:cd11272    231 INSAGDLFYTsRIVRLCKDDPKFHSYVSLPFGC------------VRGGVEYRLLQAAYLSKPGEVLARSLNITAQEDVL 298
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  349 FGVFVAVKDSSSGP--NSVVCAFPINHLDNLIEEGVERCCHPSNSSLLTRRRGLDFfqtpsfcpnppgapssRCHYFPLM 426
Cdd:cd11272    299 FAIFSKGQKQYHHPpdDSALCAFPIRAINAQIKERLQSCYQGEGNLELNWLLGKDV----------------QCTKAPVP 362
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  427 VHDSFTRVDLFNGLLGSVKVTALHV-----TRLGNVT--------VAHMGTEDGRILQV---GPSLSHLvpqscplpllf 490
Cdd:cd11272    363 IDDNFCGLDINQPLGGSTPVEGVTLytssrDRLTSVAsyvyngysVVFVGTKSGKLKKIradGPPHGGV----------- 431
                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  491 fseltclsQVEIarslnyllyVSNFSLGSsgqPVHQDV--SRLGNDLLFASGDQVFKVPIQgpGCGHFLTCWRCLRAQRf 568
Cdd:cd11272    432 --------QYEM---------VSVFKDGS---PILRDMafSIDHKYLYVMSERQVSRVPVE--SCEQYTTCGECLSSGD- 488
                          570       580
                   ....*....|....*....|...
gi 2678964124  569 MGCGWCG--DRCGRQKECPGSWQ 589
Cdd:cd11272    489 PHCGWCAlhNMCSRRDKCQRAWE 511
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
1106-1315 4.19e-24

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: 105.08  E-value: 4.19e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIH--CAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGIMLPPEGLPRVLLPYM 1182
Cdd:cd14207     15 LGRGAFGKVVQASAFGIKKSPTCrvVAVKMLKEGATASEYKALMTELKILIHIgHHLNVVNLLGACTKSGGPLMVIVEYC 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSP------------------------------QRVsAQCPGWGVSASTHLCRCSPVSSCPQNP------- 1225
Cdd:cd14207     95 KYGNLSNYLKSKrdffvtnkdtslqeelikekkeaeptggkkKRL-ESVTSSESFASSGFQEDKSLSDVEEEEedsgdfy 173
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1226 ----TVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYsVRQHrHARLPVKWMAL 1301
Cdd:cd14207    174 krplTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPDY-VRKG-DARLPLKWMAP 251
                          250
                   ....*....|....
gi 2678964124 1302 ESLQTYRFTTKSDV 1315
Cdd:cd14207    252 ESIFDKIYSTKSDV 265
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
1093-1315 4.28e-24

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: 103.18  E-value: 4.28e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQVVIhtDQVIGKGHFGVVYHGEYTDEAQnqihCAIKSLSRITevQEVEAFLREGLIMRGLHHPNILALIGIMLPPE 1172
Cdd:cd05073      8 IPRESLKL--EKKLGAGQFGEVWMATYNKHTK----VAVKTMKPGS--MSVEAFLAEANVMKTLQHDKLVKLHAVVTKEP 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 glPRVLLPYMRHGDLLRFIRSPQRVSAQCPgwgvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHR 1252
Cdd:cd05073     80 --IYIITEFMAKGSLLDFLKSDEGSKQPLP--------------------------KLIDFSAQIAEGMAFIEQRNYIHR 131
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLARGILDKEYYSvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05073    132 DLRAANILVSASLVCKIADFGLARVIEDNEYTA---REGAKFPIKWTAPEAINFGSFTIKSDV 191
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
1093-1315 1.09e-23

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: 102.46  E-value: 1.09e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQVVIHTDqvIGKGHFGVVYHGEYTDEAQnqihCAIKSLSRITevQEVEAFLREGLIMRGLHHPNILALIGIMlpPE 1172
Cdd:cd05071      6 IPRESLRLEVK--LGQGCFGEVWMGTWNGTTR----VAIKTLKPGT--MSPEAFLQEAQVMKKLRHEKLVQLYAVV--SE 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 GLPRVLLPYMRHGDLLRFIRSpqrvsaqcpgwgvSASTHLcrcspvsSCPQnptvkdLISFGLQVACGMEYLAEQKFVHR 1252
Cdd:cd05071     76 EPIYIVTEYMSKGSLLDFLKG-------------EMGKYL-------RLPQ------LVDMAAQIASGMAYVERMNYVHR 129
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLARGILDKEyYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05071    130 DLRAANILVGENLVCKVADFGLARLIEDNE-YTARQ--GAKFPIKWTAPEAALYGRFTIKSDV 189
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
1100-1315 1.26e-23

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: 101.97  E-value: 1.26e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSR-ITEVQEVEaFLREGLIMRGLHHPNILALIGIMLPPEGLpRVL 1178
Cdd:cd05063      7 ITKQKVIGAGEFGEVFRGILKMPGRKEVAVAIKTLKPgYTEKQRQD-FLSEASIMGQFSHHNIIRLEGVVTKFKPA-MII 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMRHGDLLRFIRSpqrvsaqcpgwgvsastHLCRCSPVSscpqnptvkdLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd05063     85 TEYMENGALDKYLRD-----------------HDGEFSSYQ----------LVGMLRGIAAGMKYLSDMNYVHRDLAARN 137
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLARgILDKEYYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05063    138 ILVNSNLECKVSDFGLSR-VLEDDPEGTYTTSGGKIPIRWTAPEAIAYRKFTSASDV 193
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
1081-1315 4.68e-23

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: 100.41  E-value: 4.68e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1081 DKMLLAEVKdvlipheqvvihtdqvIGKGHFGVVYHGEYTDEAQnQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPN 1160
Cdd:cd05115      3 DNLLIDEVE----------------LGSGNFGCVKKGVYKMRKK-QIDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPY 65
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1161 ILALIGImLPPEGLPRVLlPYMRHGDLLRFIrspqrvsaqcpgwgvsasthlcrcspvSSCPQNPTVKDLISFGLQVACG 1240
Cdd:cd05115     66 IVRMIGV-CEAEALMLVM-EMASGGPLNKFL---------------------------SGKKDEITVSNVVELMHQVSMG 116
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1241 MEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGI-LDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05115    117 MKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALgADDSYYKARS--AGKWPLKWYAPECINFRKFSSRSDV 190
Sema_plexin_A cd11244
The Sema domain, a protein interacting module, of Plexin A; Plexins serve as receptors of ...
65-469 5.41e-23

The Sema domain, a protein interacting module, of Plexin A; Plexins serve as receptors of semaphorins and may be the ancestor of semaphorins. Members of the Plexin A subfamily are receptors for Sema1s, Sema3s, and Sema6s, and they mediate diverse biological functions including axon guidance, cardiovascular development, and immune function. Guanylyl cyclase Gyc76C and Off-track kinase (OTK), a putative receptor tyrosine kinase, modulate Sema1a-Plexin A mediated axon repulsion. Sema3s do not interact directly with plexin A receptors, but instead bind Neuropilin-1 or Neuropilin-2 toactivate neuropilin-plexin A holoreceptor complexes. In contrast to Sema3s, Sema6s do not require neuropilins for plexin A binding. In the complex, plexin As serve as signal-transducing subunits. An increasing number of molecules that interact with the intracellular region of Plexin A have been identified; among them are IgCAMs (in axon guidance events) and Trem2-DAP12 (in immune responses). The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200505 [Multi-domain]  Cd Length: 470  Bit Score: 104.14  E-value: 5.41e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   65 DSKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGD-PGCQTCASCGPGPHG--PPNDTDTLVLVMEPGlPALVSCGSTLQ 141
Cdd:cd11244     19 HRRTGEVYVGAINRVYKLSSNLTVLVTHETGPVEDnPKCYPPPIVQTCNEPltTTNNVNKLLLIDYSE-NRLIACGSLYQ 97
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  142 GRCFLHELE---PQGEALHLAAPaclFSASNNKPEACTDCVASHLGTR----VTVVEQGHASYFYVASS----LDPELAA 210
Cdd:cd11244     98 GVCKLLRLEdlfKLGEPHHKKEH---YLSGVNESGTMFGVIVSYSNGDdklfIGTAVDGKSEYFPTLSSrkltADEESDG 174
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  211 SFSprsvsiRRLKSDTSGFQPGFPS--LSVLPkylaSYLIKYVHSFHSGDFVYFLTVQPMDVRSPPSA-----LQTRLVR 283
Cdd:cd11244    175 MFA------YVYHDEFVSSQIKIPSdtLSIIP----DFDIYYVYGFSSGNFVYFLTLQPETQLTPGDStgeqfYTSKIVR 244
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  284 LNAIEPEIGDYRELVLDChfapkrrRRSGApkslqAYQVLQAAHSAPVDAKLALDLSISEGQEVLFGVFVAVKDSSSGP- 362
Cdd:cd11244    245 LCKDDTKFYSYVEFPIGC-------TRDGV-----EYRLLQAAYLSKPGKALAQALGISEDEDVLFTIFSKGQKNRMKPp 312
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  363 -NSVVCAFPINHLDNLIEEGVERCCHPSNSSLLTRRRGLDFfqtpsfcpnppgapssRCHYFPLMVHDSFTRVDLFNGLL 441
Cdd:cd11244    313 dESALCLFTLKQINLRIKERLQSCYRGEGKLSLPWLLNKDL----------------PCINAPLQIDDNFCGLDMNQPLG 376
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|.
gi 2678964124  442 GSVKV--TALHVTR-----------LGNVTVAHMGTEDGRI 469
Cdd:cd11244    377 GSDMVegIPLFTDDrdrmtsvaayvYKGHSVVFVGTKSGKL 417
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
1106-1315 5.80e-23

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: 99.65  E-value: 5.80e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEaQNQIHCAIKSLSRITEVQEV-EAFLREGLIMRGLHHPNILALIGIMlppEGLPRVLLPYMRH 1184
Cdd:cd05116      3 LGSGNFGTVKKGYYQMK-KVVKTVAVKILKNEANDPALkDELLREANVMQQLDNPYIVRMIGIC---EAESWMLVMEMAE 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 -GDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05116     79 lGPLNKFLQKNRHV----------------------------TEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVT 130
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1264 SFTVKVADFGLARGI-LDKEYYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05116    131 QHYAKISDFGLSKALrADENYYKAQT--HGKWPVKWYAPECMNYYKFSSKSDV 181
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
1104-1315 9.05e-23

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: 100.09  E-value: 9.05e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYtDEAQNQIH--CAIKSLSRITEvQEVEAFLREGLIMRGLHHPNILALIGIMLPP--EGLpRVLL 1179
Cdd:cd14205     10 QQLGKGNFGSVEMCRY-DPLQDNTGevVAVKKLQHSTE-EHLRDFEREIEILKSLQHDNIVKYKGVCYSAgrRNL-RLIM 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFI-RSPQRVSAqcpgwgvsasthlcrcspvsscpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd14205     87 EYLPYGSLRDYLqKHKERIDH----------------------------IKLLQYTSQICKGMEYLGTKRYIHRDLATRN 138
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1259 CMLDESFTVKVADFGLARGI-LDKEYYSVRQHRHArlPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14205    139 ILVENENRVKIGDFGLTKVLpQDKEYYKVKEPGES--PIFWYAPESLTESKFSVASDV 194
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
1104-1315 2.22e-22

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: 97.98  E-value: 2.22e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDeaQNQIhCAIKS--LSRITEvQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPY 1181
Cdd:cd06606      6 ELLGKGSFGSVYLALNLD--TGEL-MAVKEveLSGDSE-EELEALEREIRILSSLKHPNIVRYLGTERTENTL-NIFLEY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGdllrfirspqrvsaqcpgwgvSASTHLCRCSPVSscpqNPTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd06606     81 VPGG---------------------SLASLLKKFGKLP----EPVVR---KYTRQILEGLEYLHSNGIVHRDIKGANILV 132
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1262 DESFTVKVADFGLARGILDKEYYSVRQHRHARLPvkWMALESLQTYRFTTKSDV 1315
Cdd:cd06606    133 DSDGVVKLADFGCAKRLAEIATGEGTKSLRGTPY--WMAPEVIRGEGYGRAADI 184
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
1106-1315 3.61e-22

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: 98.08  E-value: 3.61e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIH-CAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLP-RVLLPYMR 1183
Cdd:cd05079     12 LGEGHFGKVELCRYDPEGDNTGEqVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDGGNGiKLIMEFLP 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIrspqrvsaqcpgwgvsasthlcrcspvsscPQNPT---VKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05079     92 SGSLKEYL------------------------------PRNKNkinLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVL 141
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1261 LDESFTVKVADFGLARGI-LDKEYYSVRQHRHArlPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05079    142 VESEHQVKIGDFGLTKAIeTDKEYYTVKDDLDS--PVFWYAPECLIQSKFYIASDV 195
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
1104-1315 4.99e-22

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: 99.59  E-value: 4.99e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFG-VVYHGEY-TDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGL-HHPNILALIGiMLPPEGLPRVLLP 1180
Cdd:cd05104     41 KTLGAGAFGkVVEATAYgLAKADSAMTVAVKMLKPSAHSTEREALMSELKVLSYLgNHINIVNLLG-ACTVGGPTLVITE 119
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSpQRVSAQCPGW-------------------------------GVSAST-------HLCRCSP----- 1217
Cdd:cd05104    120 YCCYGDLLNFLRR-KRDSFICPKFedlaeaalyrnllhqremacdslneymdmkpSVSYVVptkadkrRGVRSGSyvdqd 198
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1218 -VSSCPQNPT----VKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYSVRQhrHA 1292
Cdd:cd05104    199 vTSEILEEDElaldTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIRNDSNYVVKG--NA 276
                          250       260
                   ....*....|....*....|...
gi 2678964124 1293 RLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05104    277 RLPVKWMAPESIFECVYTFESDV 299
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
1105-1315 5.98e-22

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: 97.66  E-value: 5.98e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEAQNQIH-CAIKSLSRITeVQEVEAFLREGLIMRGLHHPNILALIGIMLPPeGLP--RVLLPY 1181
Cdd:cd05081     11 QLGKGNFGSVELCRYDPLGDNTGAlVAVKQLQHSG-PDQQRDFQREIQILKALHSDFIVKYRGVSYGP-GRRslRLVMEY 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSAQCpgwgvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05081     89 LPSGCLRDFLQRHRARLDAS---------------------------RLLLYSSQICKGMEYLGSRRCVHRDLAARNILV 141
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1262 DESFTVKVADFGLARGI-LDKEYYSVRQHRHArlPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05081    142 ESEAHVKIADFGLAKLLpLDKDYYVVREPGQS--PIFWYAPESLSDNIFSRQSDV 194
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
1093-1315 7.98e-22

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: 97.06  E-value: 7.98e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQvvIHTDQVIGKGHFGVVYHGEYTDEAQnqihCAIKSLSRITEVQEveAFLREGLIMRGLHHPNILALIGIMlpPE 1172
Cdd:cd05069      9 IPRES--LRLDVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVV--SE 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 GLPRVLLPYMRHGDLLRFIRSpqrvsaqcpgwgvSASTHLcrcspvsSCPQnptvkdLISFGLQVACGMEYLAEQKFVHR 1252
Cdd:cd05069     79 EPIYIVTEFMGKGSLLDFLKE-------------GDGKYL-------KLPQ------LVDMAAQIADGMAYIERMNYIHR 132
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLARGILDKEyYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05069    133 DLRAANILVGDNLVCKIADFGLARLIEDNE-YTARQ--GAKFPIKWTAPEAALYGRFTIKSDV 192
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
1089-1315 9.61e-22

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: 96.68  E-value: 9.61e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1089 KDVL-IPHEQVVIhtDQVIGKGHFGVVYHGEYTDEAQnqihCAIKSLSRITevQEVEAFLREGLIMRGLHHPNILALIGI 1167
Cdd:cd05070      1 KDVWeIPRESLQL--IKRLGNGQFGEVWMGTWNGNTK----VAIKTLKPGT--MSPESFLEEAQIMKKLKHDKLVQLYAV 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1168 MlpPEGLPRVLLPYMRHGDLLRFIRSPQRVSAQCPgwgvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQ 1247
Cdd:cd05070     73 V--SEEPIYIVTEYMSKGSLLDFLKDGEGRALKLP--------------------------NLVDMAAQVAAGMAYIERM 124
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1248 KFVHRDLAARNCMLDESFTVKVADFGLARGILDKEyYSVRQhrHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05070    125 NYIHRDLRSANILVGNGLICKIADFGLARLIEDNE-YTARQ--GAKFPIKWTAPEAALYGRFTIKSDV 189
Sema_plexin_A1 cd11271
The Sema domain, a protein interacting module, of Plexin A1; Plexin A1 is found in both the ...
66-472 1.20e-21

The Sema domain, a protein interacting module, of Plexin A1; Plexin A1 is found in both the nervous and immune systems. Its external Sema domain is also shared by semaphorin proteins. In the nervous system, Plexin A1 mediates Sema3A axon guidance function by interacting with the Sema3A coreceptor neuropilin, resulting in actin depolarization and cell repulsion. In the immune system, Plexin A1 mediates Sema6D signaling by binding to the Sema6D-Trem2-DAP12 complex on immune cells and osteoclasts to promote Rac activation and DAP12 phosphorylation. In gene profiling experiments, Plexin A1 was identified as a CIITA (class II transactivator) regulated gene in primary dendritic cells (DCs). The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200532 [Multi-domain]  Cd Length: 474  Bit Score: 100.04  E-value: 1.20e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   66 SKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGD-------PGCQTCascgpgPHG--PPNDTDTLVLVMEPGlPALVSC 136
Cdd:cd11271     21 NKTGEVYVGAVNRIYKLSNNLTLLRTHVTGPVEDnekcyppPSVQSC------PHGlgTTNNVNKLLLVDYAA-NRLIAC 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  137 GSTLQGRC-FLH--ELEPQGEALHlaapaclfsasnNKPEACTDCVASHLGTRVTVVEQGHASYFYVASSLD--PELAAS 211
Cdd:cd11271     94 GSASQGICqFLRldDLFKLGEPHH------------RKEHYLSSVNESGTMSGVIIEVGNGQNKLFVGTPIDgkSEYFPT 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  212 FSPRSVSIRRLKSDTSGF---------QPGFPS--LSVLPkylaSYLIKYVHSFHSGDFVYFLTVQpMDVR--SPPSA-- 276
Cdd:cd11271    162 LSSRKLMANEENAEMFGFvyqdefvssQLKIPSdtLSKFP----TFDIYYVYSFSSEQFVYYLTLQ-LDTQltSPDSTge 236
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  277 --LQTRLVRLNAIEPEIGDYRELVLDCHfapkrrrrsgapKSLQAYQVLQAAHSAPVDAKLALDLSISEGQEVLFGVFVA 354
Cdd:cd11271    237 qfFTSKIVRLCVDDPKFYSYVEFPIGCE------------QDGVEYRLIQDAYLSKPGKALAKQLGISEREDILFTVFSQ 304
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  355 VKDSSSGP--NSVVCAFPINHLDNLIEEGVERCchpsnsslltrRRGLDFFQTPSFCPNPPGAPSSrchyfPLMVHDSFT 432
Cdd:cd11271    305 GQKNRVKPpkESVLCLFTLKKIKDKIKERIQSC-----------YRGEGKLSLPWLLNKELGCINS-----PLQIDDNFC 368
                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124  433 RVDLFNGLLGSVKV--TALHVTR---LGNV--------TVAHMGTEDGRILQV 472
Cdd:cd11271    369 GQDFNQPLGGTVTIegTPLFVDKedgMTSVaaydyrgrTVVFAGTRSGRIKKI 421
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
1104-1302 1.86e-21

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: 95.73  E-value: 1.86e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGE-YTDEAQNQIhcAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLppEGLPRVL-LPY 1181
Cdd:cd05042      1 QEIGNGWFGKVLLGEiYSGTSVAQV--VVKELKASANPKEQDTFLKEGQPYRILQHPNILQCLGQCV--EAIPYLLvMEF 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSpqrvsaqcpgwgvsasthlcrCSPVSSCPQNPtvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05042     77 CDLGDLKAYLRS---------------------EREHERGDSDT--RTLQRMACEVAAGLAHLHKLNFVHSDLALRNCLL 133
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 2678964124 1262 DESFTVKVADFGLARGILDKEYYSVRQHRHarLPVKWMALE 1302
Cdd:cd05042    134 TSDLTVKIGDYGLAHSRYKEDYIETDDKLW--FPLRWTAPE 172
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
1104-1315 2.36e-21

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: 95.74  E-value: 2.36e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVV--YHGEYTDEAQNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMlpPEGLPRVLLPY 1181
Cdd:cd05080     10 RDLGEGHFGKVslYCYDPTNDGTGEM-VAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCC--SEQGGKSLQLI 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRH---GDLLRFIrspqrvsaqcpgwgvsasthlcrcspvsscPQNP-TVKDLISFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd05080     87 MEYvplGSLRDYL------------------------------PKHSiGLAQLLLFAQQICEGMAYLHSQHYIHRDLAAR 136
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1258 NCMLDESFTVKVADFGLARGILD-KEYYSVRQHRHArlPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05080    137 NVLLDNDRLVKIGDFGLAKAVPEgHEYYRVREDGDS--PVFWYAPECLKEYKFYYASDV 193
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
1106-1315 2.73e-21

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: 95.42  E-value: 2.73e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPeGLPRVLLPYMRHG 1185
Cdd:cd14066      1 IGSGGFGTVYKGVL----ENGTVVAVKRLNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLES-DEKLLVYEYMPNG 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIrspqrvsaqcpgwgvsastHLCRCSPVSSCPQnptvkdLISFGLQVACGMEYLAEQKF---VHRDLAARNCMLD 1262
Cdd:cd14066     76 SLEDRL-------------------HCHKGSPPLPWPQ------RLKIAKGIARGLEYLHEECPppiIHGDIKSSNILLD 130
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1263 ESFTVKVADFGLARgILDKEYYSVRQHRHARLpVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14066    131 EDFEPKLTDFGLAR-LIPPSESVSKTSAVKGT-IGYLAPEYIRTGRVSTKSDV 181
Sema pfam01403
Sema domain; The Sema domain occurs in semaphorins, which are a large family of secreted and ...
323-528 2.99e-21

Sema domain; The Sema domain occurs in semaphorins, which are a large family of secreted and transmembrane proteins, some of which function as repellent signals during axon guidance. Sema domains also occur in the hepatocyte growth factor receptor and Swiss:P51805


Pssm-ID: 460197 [Multi-domain]  Cd Length: 180  Bit Score: 92.33  E-value: 2.99e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  323 LQAAHSAPVDAKLALDlsisegqEVLFGVFVAVKdSSSGPNSVVCAFPINHLDNLIEeGVERCCHPSNSSLLtRRRGLDF 402
Cdd:pfam01403    1 LQDVFVLKPGAGDALD-------TVLYGVFTTQW-SNSIGGSAVCAFSLSDINAVFE-GPFKEQEKSDSKWL-PYTGKVP 70
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  403 FQTPSFCPNPP---GAPSSRC---HYFPLMVH--DSFTRVDLFNGllGSVKVTALHVTRL----GNVTVAHMGTEDGRIL 470
Cdd:pfam01403   71 YPRPGTCINDPlrlDLPDSVLnfvKDHPLMDEavQPVGGRPLLVR--TGVRLTSIAVDRVqaldGNYTVLFLGTDDGRLH 148
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124  471 QVgpslshlvpqscplpllffseltclsqveIARSLNYLLYVSNFSLGSSGQPVHQDV 528
Cdd:pfam01403  149 KV-----------------------------VLVGSEESHIIEEIQVFPEPQPVLNLL 177
Sema_plexin_A3 cd11273
The Sema domain, a protein interacting module, of Plexin A3; Plexin-A3 forms a receptor ...
67-385 1.80e-20

The Sema domain, a protein interacting module, of Plexin A3; Plexin-A3 forms a receptor complex with neuropilin-2 and transduces signals for class 3 semaphorins in the nervous system. Both plexins A3 and A4 are essential for normal sympathetic neuron development. They function cooperatively to regulate the migration of sympathetic neurons, and differentially to guide sympathetic axons. Both plexins A3 and A4 are not required for guiding neural crest precursors prior to reaching the sympathetic anlagen. Plexin A3 is a major driving force for intraspinal motor growth cone guidance. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200534 [Multi-domain]  Cd Length: 469  Bit Score: 96.54  E-value: 1.80e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   67 KNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGD-------PGCQTCAScgpgPHGPPNDTDTLVLVMEPGlPALVSCGST 139
Cdd:cd11273     21 VTGEVFVGAVNRVYKLSANLTELRAHVTGPVEDnarcyppPSVRVCAH----RLAPVDNVNKLLLVDYAG-NRLVACGSI 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  140 LQGRCFLHELEpqgEALHLAAPaclfsasNNKPEACTDCVASHLGTRVTVVEQGHA-SYFYVASSLDPElaASFSPrSVS 218
Cdd:cd11273     96 WQGVCQFLRLE---DLFKLGEP-------HHRKEHYLSGAQEPDSMAGVIVEQGKGpSKLFVGTAIDGK--SEYFP-TLS 162
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  219 IRRLKSDTSG-------FQPGF-------PS--LSVLPkylaSYLIKYVHSFHSGDFVYFLTVQpMDVRSPPSA------ 276
Cdd:cd11273    163 SRKLISDEDSadmfslvYQDEFvssqikiPSdtLSLYP----AFDIYYVYGFVSASFVYFLTLQ-LDTQQTLLDtagekf 237
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  277 LQTRLVRLNAIEPEIGDYRELVLDChfapkrrrrsgaPKSLQAYQVLQAAHSAPVDAKLALDLSISEGQEVLFGVFVAVK 356
Cdd:cd11273    238 FTSKIVRMCANDTEFYSYVEFPLGC------------SKDGVEYRLVQAAHLAKPGLLLAQALGVPEDEDVLFTIFSQGQ 305
                          330       340       350
                   ....*....|....*....|....*....|.
gi 2678964124  357 DSSSGP--NSVVCAFPINHLDNLIEEGVERC 385
Cdd:cd11273    306 KNRASPprETILCLFTLSNINAHIRERIQSC 336
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
1104-1282 2.04e-20

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: 92.63  E-value: 2.04e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEaQNQIHCAIKSLSRITEVQE-VEAFL-REGLIMRGLHHPNILALIGIMlppEGLPRV--LL 1179
Cdd:cd14080      6 KTIGEGSYSKVKLAEYTKS-GLKEKVACKIIDKKKAPKDfLEKFLpRELEILRKLRHPNIIQVYSIF---ERGSKVfiFM 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIRSPQRVSAqcpgwgvsastHLCRcspvsscpqnptvkdliSFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd14080     82 EYAEHGDLLEYIQKRGALSE-----------SQAR-----------------IWFRQLALAVQYLHSLDIAHRDLKCENI 133
                          170       180
                   ....*....|....*....|...
gi 2678964124 1260 MLDESFTVKVADFGLARGILDKE 1282
Cdd:cd14080    134 LLDSNNNVKLSDFGFARLCPDDD 156
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
1104-1308 4.74e-20

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: 91.94  E-value: 4.74e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGE-YTDEAQNQIhcAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGimLPPEGLPRVL-LPY 1181
Cdd:cd14206      3 QEIGNGWFGKVILGEiFSDYTPAQV--VVKELRVSAGPLEQRKFISEAQPYRSLQHPNILQCLG--LCTETIPFLLiMEF 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRspqrvsAQCPGWGVSasthlcrcspvsscPQNPTvKDLISF---GLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd14206     79 CQLGDLKRYLR------AQRKADGMT--------------PDLPT-RDLRTLqrmAYEITLGLLHLHKNNYIHSDLALRN 137
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1259 CMLDESFTVKVADFGLARGILDKEYYSVRQhrhaRL--PVKWMALESLQTYR 1308
Cdd:cd14206    138 CLLTSDLTVRIGDYGLSHNNYKEDYYLTPD----RLwiPLRWVAPELLDELH 185
Sema_plexin_A4 cd11274
The Sema domain, a protein interacting module, of Plexin A4; Plexin A4 forms a receptor ...
65-385 4.91e-20

The Sema domain, a protein interacting module, of Plexin A4; Plexin A4 forms a receptor complex with neuropilins (NRPs) and transduces signals for class 3 semaphorins in the nervous system. It regulates facial nerve development by functioning as a receptor for Sema3A/NRP1. Both plexins A3 and A4 are essential for normal sympathetic development. They function both cooperatively, to regulate the migration of sympathetic neurons, and differentially, to guide sympathetic axons. Plexin A4 is also expressed in lymphoid tissues and functions in the immune system. It negatively regulates T lymphocyte responses. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200535 [Multi-domain]  Cd Length: 473  Bit Score: 95.02  E-value: 4.91e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   65 DSKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGD-PGC------QTCAScgpgPHGPPNDTDTLVLvMEPGLPALVSCG 137
Cdd:cd11274     19 DERTGHIYLGAVNRIYKLSSDLKVLVTHQTGPDEDnPKCypprivQTCNE----PLTLTNNINKMLL-IDYKENRLIACG 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  138 STLQGRCFLHELEpqgEALHLAAPAclfsasnNKPEACTDCVaSHLGTRVTVVEQGHAS--YFYVASSLD--PELAASFS 213
Cdd:cd11274     94 SLYQGICKLLRLD---DLFKLGEPF-------HKKEHYLSGV-NESGSVFGVIVSYSNLddKLFIATAVDgkPEYFPTIS 162
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  214 PRSV--------------------SIRRLKSDTSGFQPGFPslsvlpkylasylIKYVHSFHSGDFVYFLTVQPMDVRSP 273
Cdd:cd11274    163 SRKLtknseadgmfayvfhdefvaSMIKIPSDTFTIIPDFD-------------IYYIYGFSSGNFVYFLTLQPEMISPP 229
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  274 PSALQ-----TRLVRLNAIEPEIGDYRELVLDChfapkrrRRSGApkslqAYQVLQAAHSAPVDAKLALDLSISEGQEVL 348
Cdd:cd11274    230 GSTTKeqvytSKLVRLCKEDTAFNSYVEVPIGC-------EKNGV-----EYRLLQAAYLSKAGAILARSLGVGPDDDIL 297
                          330       340       350
                   ....*....|....*....|....*....|....*....
gi 2678964124  349 FGVFVA--VKDSSSGPNSVVCAFPINHLDNLIEEGVERC 385
Cdd:cd11274    298 FTVFSKgqKRKMKSLDESALCIFVLKEINDRIKDRLQSC 336
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
1106-1315 1.16e-19

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: 90.64  E-value: 1.16e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgEYTDEAQNQIhCAIKSLSRITEvqEVEA-FLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRH 1184
Cdd:cd14154      1 LGKGFFGQAI--KVTHRETGEV-MVMKELIRFDE--EAQRnFLKEVKVMRSLDHPNVLKFIGVLYKDKKL-NLITEYIPG 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSPQRVSAqcpgWgvsasthlcrcspvsscPQNptvkdlISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd14154     75 GTLKDVLKDMARPLP----W-----------------AQR------VRFAKDIASGMAYLHSMNIIHRDLNSHNCLVRED 127
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1265 FTVKVADFGLARGILDKEYYS-----VRQHRHARLPVK-----------WMALESLQTYRFTTKSDV 1315
Cdd:cd14154    128 KTVVVADFGLARLIVEERLPSgnmspSETLRHLKSPDRkkrytvvgnpyWMAPEMLNGRSYDEKVDI 194
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
1226-1315 1.20e-19

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: 93.17  E-value: 1.20e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1226 TVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGIL-DKEYYSvrqHRHARLPVKWMALESL 1304
Cdd:cd05105    235 TTLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARDIMhDSNYVS---KGSTFLPVKWMAPESI 311
                           90
                   ....*....|.
gi 2678964124 1305 QTYRFTTKSDV 1315
Cdd:cd05105    312 FDNLYTTLSDV 322
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
1093-1315 1.64e-19

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: 92.77  E-value: 1.64e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1093 IPHEQVVIhtDQVIGKGHFGVVY----HGeyTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLH-HPNILALIGi 1167
Cdd:cd05107     34 MPRDNLVL--GRTLGSGAFGRVVeataHG--LSHSQSTMKVAVKMLKSTARSSEKQALMSELKIMSHLGpHLNIVNLLG- 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1168 MLPPEGLPRVLLPYMRHGDLLRFIRSPQRV-------SAQCPGWGVSAST--------HLC------------------- 1213
Cdd:cd05107    109 ACTKGGPIYIITEYCRYGDLVDYLHRNKHTflqyyldKNRDDGSLISGGStplsqrksHVSlgsesdggymdmskdesad 188
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1214 ----------------RCSPVSS-----CPQNP---------------TVKDLISFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd05107    189 yvpmqdmkgtvkyadiESSNYESpydqyLPSAPertrrdtlinespalSYMDLVGFSYQVANGMEFLASKNCVHRDLAAR 268
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1258 NCMLDESFTVKVADFGLARGIL-DKEYYSvrqHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05107    269 NVLICEGKLVKICDFGLARDIMrDSNYIS---KGSTFLPLKWMAPESIFNNLYTTLSDV 324
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
1104-1278 9.02e-19

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: 89.12  E-value: 9.02e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTdeaQNQIHCAIKSLSRITEVQeVEA--FLREGLIMRGLHHPNILALIGIMLPPEgLPR----- 1176
Cdd:cd07834      6 KPIGSGAYGVVCSAYDK---RTGRKVAIKKISNVFDDL-IDAkrILREIKILRHLKHENIIGLLDILRPPS-PEEfndvy 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 VLLPYMRHgDLLRFIRSPQRVSAQcpgwgvsastHLCRcspvsscpqnptvkdlisFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd07834     81 IVTELMET-DLHKVIKSPQPLTDD----------HIQY------------------FLYQILRGLKYLHSAGVIHRDLKP 131
                          170       180
                   ....*....|....*....|..
gi 2678964124 1257 RNCMLDESFTVKVADFGLARGI 1278
Cdd:cd07834    132 SNILVNSNCDLKICDFGLARGV 153
IPT_plexin_repeat1 cd01180
First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are ...
595-709 6.01e-18

First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present preceeded by SEMA (semaphorin) and PSI (plexin, semaphorin, integrin) domains.


Pssm-ID: 238585  Cd Length: 94  Bit Score: 80.05  E-value: 6.01e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  595 PEITEFHPHSGPLRGTTRLTLCGSNFYLRPDGVvpegTHQITVGQSPCRLLP--KDSSTR------RSGSQkefieelec 666
Cdd:cd01180      1 PVITEFFPLSGPLEGGTRLTICGSNLGLRKNDV----RHGVRVGGVPCNPEPpeYSSSEKivcttgPAGNP--------- 67
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2678964124  667 elepletqaVGTTNISLLITNMPAGKHfrvegvsVREDFSFME 709
Cdd:cd01180     68 ---------VFNGPVEVTVGHGSFRTE-------SSEGFSFVD 94
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
1105-1315 6.29e-18

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: 85.14  E-value: 6.29e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEaqnqiHCAIKSLSRITE---VQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd14061      1 VIGVGGFGKVYRGIWRGE-----EVAVKAARQDPDediSVTLENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVM-EY 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIrspqrVSAQCPgwgvsasthlcrcspvsscpqnPTVkdLISFGLQVACGMEYLAEQKFV---HRDLAARN 1258
Cdd:cd14061     75 ARGGALNRVL-----AGRKIP----------------------PHV--LVDWAIQIARGMNYLHNEAPVpiiHRDLKSSN 125
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1259 CMLDESF--------TVKVADFGLARGIldkeyysvrqHRHARLPV----KWMALESLQTYRFTTKSDV 1315
Cdd:cd14061    126 ILILEAIenedlenkTLKITDFGLAREW----------HKTTRMSAagtyAWMAPEVIKSSTFSKASDV 184
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
1106-1315 7.74e-18

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: 85.01  E-value: 7.74e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGV---VYHGEyTDEAQnqihcAIKSLSRITEvQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYM 1182
Cdd:cd14221      1 LGKGCFGQaikVTHRE-TGEVM-----VMKELIRFDE-ETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRL-NFITEYI 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSpqrVSAQCPgWGvsasthlcrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd14221     73 KGGTLRGIIKS---MDSHYP-WS-----------------------QRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVR 125
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1263 ESFTVKVADFGLARGILDKEYYSV------RQHRHARLPV----KWMALESLQTYRFTTKSDV 1315
Cdd:cd14221    126 ENKSVVVADFGLARLMVDEKTQPEglrslkKPDRKKRYTVvgnpYWMAPEMINGRSYDEKVDV 188
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
1106-1315 8.00e-18

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: 85.00  E-value: 8.00e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgEYTDEAQNQIhCAIKSLSRITEvQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd14222      1 LGKGFFGQAI--KVTHKATGKV-MVMKELIRCDE-ETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRL-NLLTEFIEGG 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSpqrvsaqcpgwgvsasthlcrcspVSSCPQNPTVkdliSFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd14222     76 TLKDFLRA------------------------DDPFPWQQKV----SFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDK 127
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1266 TVKVADFGLARGILD------------KEYYSVRQHRHARLPV----KWMALESLQTYRFTTKSDV 1315
Cdd:cd14222    128 TVVVADFGLSRLIVEekkkpppdkpttKKRTLRKNDRKKRYTVvgnpYWMAPEMLNGKSYDEKVDI 193
Sema_plexin_B2 cd11276
The Sema domain, a protein interacting module, of Plexin B2; Plexin B2 serves as the receptor ...
62-549 4.48e-17

The Sema domain, a protein interacting module, of Plexin B2; Plexin B2 serves as the receptor of Sema4C and Sema4G. By signaling the effect of Sema4C and Sema4G, the plexin B2 receptor plays important roles in neural tube closure and cerebellar granule cell development. Mice lacking Plexin B2 demonstrated defects in closure of the neural tube and disorganization of the embryonic brain. In developing kidney, Sema4C-Plexin B2 signaling modulates ureteric branching. Plexin B2 is expressed both in the pretubular aggregates and the ureteric epithelium in the developing kidney. Deletion of Plexin B2 results in renal hypoplasia and occasional double ureters. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200537 [Multi-domain]  Cd Length: 449  Bit Score: 85.60  E-value: 4.48e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   62 VYEDSKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGD-PGCQ---TCASCGPGphgppNDTDTL--VLVMEPGLPALVS 135
Cdd:cd11276     11 LVVDPQTGRVYLGAVNALYQLDADLQLESRVETGPKKDnKKCTppiEENQCTEA-----KMTDNYnkLLLLDSANKTLVV 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  136 CGSTLQGRCFLHELEPQGEALHLaapaclfsaSNNKPE----ACTDCVASHLGTrVTVVEQGHASYFYVASSLDPelaaS 211
Cdd:cd11276     86 CGSLFKGICSLRNLSNISEVIYY---------SDTSGEksfvASNDEGVSTVGL-ISSLKPGNDRVFFVGKGNGS----N 151
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  212 FSPRSVSIRRL--KSDTSGFQPGFPSLSVLPKYLASYLIKYVHSFHSGDFVYFLTVQPMdvrSPPSALQTRLVRLNAIEP 289
Cdd:cd11276    152 DNGKIISTRLLqnYDDREVFENYIDAATVKSAYVSRYTQQFRYAFEDNNYVYFLFNQQL---GHPDKNRTLIARLCENDH 228
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  290 EIGDYRELVLDChfapkrrrRSGApkslQAYQVLQAAH-SAPVDAKLALDLSISEGQEVLFGVFVavKDSSSGPNSVVCA 368
Cdd:cd11276    229 HYYSYTEMDLNC--------RDGA----NAYNKCQAAYvSTPGKELAQNYGNSILSDKVLFAVFS--RDEKDSGESALCM 294
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  369 FPINHLDNLIEEGVERCchpsnssLLTRRRGLDFFQTP--SFCPNPPG--APSSRCHY--------FPLMVHDSFTrvdL 436
Cdd:cd11276    295 FPLKSINAKMEANREAC-------YTGTIDDRDVFYKPfhSQKDIICGshQQKNSKSFpcgsehlpYPLGSRDELA---L 364
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  437 FNGLL--GSVKVTALHVTRLGNVTVAHMGTEDGRILQVgpslsHLVPQSCPlpllffseltclsqveiarslnyllYVSn 514
Cdd:cd11276    365 TAPVLqrGGLNLTAVTVAVENGHTVAFLGTSDGRILKV-----HLSPDPEE-------------------------YNS- 413
                          490       500       510
                   ....*....|....*....|....*....|....*..
gi 2678964124  515 fSLGSSGQPVHQDV--SRLGNDLLFASGDQVFKVPIQ 549
Cdd:cd11276    414 -ILIEKNKPVNKDLvlDKTLEHLYIMTEDKVFRLPVQ 449
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
1106-1315 5.10e-17

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: 82.15  E-value: 5.10e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIhcaIKSLSRITEVQeveAFLREGLIMRGLHHPNILALIGIMLPpEGLPRVLLPYMRHG 1185
Cdd:cd14065      1 LGKGFFGEVYKVTHRETGKVMV---MKELKRFDEQR---SFLKEVKLMRRLSHPNILRFIGVCVK-DNKLNFITEYVNGG 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSPQrvsAQCPgWGVSasthlcrcspvsscpqnptvkdlISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES- 1264
Cdd:cd14065     74 TLEELLKSMD---EQLP-WSQR-----------------------VSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREAn 126
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1265 --FTVKVADFGLARGILDkeYYSVRQHRHARLPV----KWMALESLQTYRFTTKSDV 1315
Cdd:cd14065    127 rgRNAVVADFGLAREMPD--EKTKKPDRKKRLTVvgspYWMAPEMLRGESYDEKVDV 181
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
1103-1315 5.56e-17

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: 82.25  E-value: 5.56e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1103 DQVIGKGHFGVVYhgEYTDEAQNQIhCAIK--SLSRITEVQEVEAFLREGLIMRGLHHPNILALIGImLPPEGLPRVLLP 1180
Cdd:cd14014      5 VRLLGRGGMGEVY--RARDTLLGRP-VAIKvlRPELAEDEEFRERFLREARALARLSHPNIVRVYDV-GEDDGRPYIVME 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd14014     81 YVEGGSLADLLRERGPL----------------------------PPREALRILAQIADALAAAHRAGIVHRDIKPANIL 132
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1261 LDESFTVKVADFGLARGILDkeyySVRQHRHARL--PVkWMALESLQTYRFTTKSDV 1315
Cdd:cd14014    133 LTEDGRVKLTDFGIARALGD----SGLTQTGSVLgtPA-YMAPEQARGGPVDPRSDI 184
Sema_plexin_B cd11245
The Sema domain, a protein interacting module, of Plexin B; Plexins, which contain semaphorin ...
62-478 6.63e-17

The Sema domain, a protein interacting module, of Plexin B; Plexins, which contain semaphorin domains, function as receptors of semaphorins and may be the ancestors of semaphorins. There are three members of the Plexin B subfamily, namely B1, B2 and B3. Plexins B1, B2 and B3 are receptors for Sema4D, Sema4C and Sema4G, and Sema5A, respectively. The activation of plexin B1 by Sema4D produces an acute collapse of axonal growth cones in hippocampal and retinal neurons over the early stages of neurite outgrowth and promotes branching and complexity. By signaling the effect of Sema4C and Sema4G, the plexin B2 receptor is critically involved in neural tube closure and cerebellar granule cell development. Plexin B3, the receptor of Sema5A, is a highly potent stimulator of neurite outgrowth of primary murine cerebellar neurons. Plexin B3 has been linked to verbal performance and white matter volume in human brain. Small GTPases play important roles in plexin B signaling. Plexin B1 activates Rho through Rho-specific guanine nucleotide exchange factors, leading to neurite retraction. Plexin B1 possesses an intrinsic GTPase-activating protein activity for R-Ras and induces growth cone collapse through R-Ras inactivation. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200506 [Multi-domain]  Cd Length: 440  Bit Score: 84.98  E-value: 6.63e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   62 VYEDSKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGD-PGC---QTCASCgpgPHGPPNDTDTLVLVMEPGLPALVSCG 137
Cdd:cd11245      5 LAQDPQTGRLYLGAVNGLFQLSPNLQLESRADTGPKKDsPQClppITAAEC---PQAKETDNFNKLLLVNSANGTLVVCG 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  138 STLQGRCFLHEL----------EPQGEALHLAApaclfsasnNKPEACTdcvashlgtrVTVVEQGHA--SYFYVASSLD 205
Cdd:cd11245     82 SLFQGVCELRNLnsvnkplyrpETPGDKQYVAA---------NEPSVST----------VGLISYFKDglSLLFVGRGYT 142
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  206 PELAASFSPrsVSIRRLKSdtSGFQPGFPSL---SVLPKYLASYLIKYVHSFHSGDFVYFLTvqpmdVRSP---PSALQT 279
Cdd:cd11245    143 SSLSGGIPP--ITTRLLQE--HGEMDAFSNEveaKLVVGSASRYHHDFVYAFADNGYIYFLF-----SRRPgtaDSTKRT 213
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  280 RLVRLNAIEPEIGDYRELVLDCHFAPKRRrrsgapkslqaYQVLQAAHSAPVDAKLaldlsiseGQEVLFGVFVAVKDSS 359
Cdd:cd11245    214 YISRLCENDHHYYSYVELPLNCTVNQENT-----------YNLVQAAYLAKPGKVL--------NGKVLFGVFSADEAST 274
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  360 SGPN--SVVCAFPINHLDNLIEEGVERCCHPSNSSLLTRRRGLDFFQTPSFCPNPP---------GA---PSSRCHYFPL 425
Cdd:cd11245    275 AAPDgrSALCMYPLSSVDARFERTRESCYTGEGLEDDKPETAYIEYNVKSICKTLPdknvkaypcGAehtPSPLASRYPL 354
                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124  426 MVHDSFTRVDlfngllgsvKVTALHVTRLGNVTVAHMGTEDGRILQV--GPSLSH 478
Cdd:cd11245    355 AAKPILTRND---------MLTAVAVAVENGHTIAFLGDSGGQLHKVylDPNHTD 400
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
1106-1276 6.98e-17

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: 82.61  E-value: 6.98e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgeytdEAQNQIHCAIKSLSRITEVQEVEAF----LREGLIMRGLHHPNILALIGIMLPPEGLPR----- 1176
Cdd:cd07840      7 IGEGTYGQVY------KARNKKTGELVALKKIRMENEKEGFpitaIREIKLLQKLDHPNVVRLKEIVTSKGSAKYkgsiy 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 VLLPYMRHgDLLRFIRSPqrvsaqcpgwgvsaSTHLcrcspvsSCPQnptVKdliSFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd07840     81 MVFEYMDH-DLTGLLDNP--------------EVKF-------TESQ---IK---CYMKQLLEGLQYLHSNGILHRDIKG 132
                          170       180
                   ....*....|....*....|
gi 2678964124 1257 RNCMLDESFTVKVADFGLAR 1276
Cdd:cd07840    133 SNILINNDGVLKLADFGLAR 152
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
1106-1302 1.36e-16

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: 81.57  E-value: 1.36e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEyTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMlpPEGLPRVL-LPYMRH 1184
Cdd:cd05087      5 IGHGWFGKVFLGE-VNSGLSSTQVVVKELKASASVQDQMQFLEEAQPYRALQHTNLLQCLAQC--AEVTPYLLvMEFCPL 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSpqrvsaqcpgwgvsasthlcrCSPVSSCPQNPTVkdLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd05087     82 GDLKGYLRS---------------------CRAAESMAPDPLT--LQRMACEVACGLLHLHRNNFVHSDLALRNCLLTAD 138
                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 2678964124 1265 FTVKVADFGLARGILDKEYYSVRQHRHarLPVKWMALE 1302
Cdd:cd05087    139 LTVKIGDYGLSHCKYKEDYFVTADQLW--VPLRWIAPE 174
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
1104-1315 2.01e-16

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 83.91  E-value: 2.01e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQnqiHCAIKSL--SRITEVQEVEAFLREGLIMRGLHHPNILALIGImLPPEGLPRVLLPY 1181
Cdd:COG0515     13 RLLGRGGMGVVYLARDLRLGR---PVALKVLrpELAADPEARERFRREARALARLNHPNIVRVYDV-GEEDGRPYLVMEY 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:COG0515     89 VEGESLADLLRRRGPLP----------------------------PAEALRILAQLAEALAAAHAAGIVHRDIKPANILL 140
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1262 DESFTVKVADFGLARgILDKEyySVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:COG0515    141 TPDGRVKLIDFGIAR-ALGGA--TLTQTGTVVGTPGYMAPEQARGEPVDPRSDV 191
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
1105-1315 2.20e-16

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: 80.32  E-value: 2.20e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTdeaQNQIHCAIKSLSrITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRH 1184
Cdd:cd05122      7 KIGKGGFGVVYKARHK---KTGQIVAIKKIN-LESKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDEL-WIVMEFCSG 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLrfirspqrvsaqcpgwgvSASTHLCRCSPvsscpqnptvKDLISF-GLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd05122     82 GSLK------------------DLLKNTNKTLT----------EQQIAYvCKEVLKGLEYLHSHGIIHRDIKAANILLTS 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1264 SFTVKVADFGLArGILDKEyySVRQHRHARLPvkWMALESLQTYRFTTKSDV 1315
Cdd:cd05122    134 DGEVKLIDFGLS-AQLSDG--KTRNTFVGTPY--WMAPEVIQGKPYGFKADI 180
IPT_PCSR cd00603
IPT domain of Plexins and Cell Surface Receptors (PCSR) and related proteins . This subgroup ...
710-794 3.63e-16

IPT domain of Plexins and Cell Surface Receptors (PCSR) and related proteins . This subgroup contains IPT domains of plexins, receptors, like the plasminogen-related growth factor receptors, the hepatocyte growth factor-scatter factors, and the macrophage-stimulating receptors and of fibrocystin. Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT_PCSR domain present preceeded by SEMA (semaphorin) and PSI (plexin, semaphorin, integrin) domains.


Pssm-ID: 238337 [Multi-domain]  Cd Length: 90  Bit Score: 74.80  E-value: 3.63e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  710 PMLTSIKPDFGPRAGGTYLTLEGQSLSVGT-SRAVLVNGTQCRLEQVSEEKILCVTPPGAGTASVPLRLQIGGAEVRGSR 788
Cdd:cd00603      1 PVITSISPSSGPLSGGTRLTITGSNLGSGSpRVRVTVGGVPCKVLNVSSTEIVCRTPAAATPGEGPVEVTVDGANVSARV 80
                           90
                   ....*....|
gi 2678964124  789 ----TFHYKE 794
Cdd:cd00603     81 lsntTFTYVE 90
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
1104-1308 8.79e-16

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: 79.14  E-value: 8.79e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGE-YTDEAQNQIhcAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLppEGLPRVLL-PY 1181
Cdd:cd05086      3 QEIGNGWFGKVLLGEiYTGTSVARV--VVKELKASANPKEQDDFLQQGEPYYILQHPNILQCVGQCV--EAIPYLLVfEF 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRvsaqcpgwgvsastHLCRcspvsscpqNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05086     79 CDLGDLKTYLANQQE--------------KLRG---------DSQIMLLQRMACEIAAGLAHMHKHNFLHSDLALRNCYL 135
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 2678964124 1262 DESFTVKVADFGLARGILDKEYYSVRQHRHArlPVKWMALESLQTYR 1308
Cdd:cd05086    136 TSDLTVKVGDYGIGFSRYKEDYIETDDKKYA--PLRWTAPELVTSFQ 180
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
1106-1276 1.60e-15

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: 78.03  E-value: 1.60e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQnqiHCAIKSLSRitevQEVEAFLREGL-----IMRGLHHPNILALIGIMLPPEGLPRVlLP 1180
Cdd:cd14009      1 IGRGSFATVWKGRHKQTGE---VVAIKEISR----KKLNKKLQENLeseiaILKSIKHPNIVRLYDVQKTEDFIYLV-LE 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqNPTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd14009     73 YCAGGDLSQYIRKRGRLP-------------------------EAVAR---HFMQQLASGLKFLRSKNIIHRDLKPQNLL 124
                          170
                   ....*....|....*....
gi 2678964124 1261 L---DESFTVKVADFGLAR 1276
Cdd:cd14009    125 LstsGDDPVLKIADFGFAR 143
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
1100-1315 3.45e-15

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: 77.27  E-value: 3.45e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLL 1179
Cdd:cd05064      7 IKIERILGTGRFGELCRGCLKLPSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRGNTM-MIVT 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIRspqRVSAQCpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd05064     86 EYMSNGALDSFLR---KHEGQL------------------------VAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKV 138
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1260 MLDESFTVKVADFG-LARGILDKEYYSVRqhrhARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd05064    139 LVNSDLVCKISGFRrLQEDKSEAIYTTMS----GKSPVLWAAPEAIQYHHFSSASDV 191
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
1104-1276 3.59e-15

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: 76.79  E-value: 3.59e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTdeaQNQIHCAIKSLSRITEVQEVEAFL-REGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYM 1182
Cdd:cd14003      6 KTLGEGSFGKVKLARHK---LTGEKVAIKIIDKSKLKEEIEEKIkREIEIMKLLNHPNIIKLYEVIETENKIYLVM-EYA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqNPTVKDLisFGlQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd14003     82 SGGELFDYIVNNGRLS-------------------------EDEARRF--FQ-QLISAVDYCHSNGIVHRDLKLENILLD 133
                          170
                   ....*....|....
gi 2678964124 1263 ESFTVKVADFGLAR 1276
Cdd:cd14003    134 KNGNLKIIDFGLSN 147
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
1104-1283 3.85e-15

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: 77.52  E-value: 3.85e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGeyTDEAQNQIhCAIKslsRITEVQEVEAF----LREGLIMRGLHHPNILALIGIMLPPEGLPRVLl 1179
Cdd:cd07829      5 EKLGEGTYGVVYKA--KDKKTGEI-VALK---KIRLDNEEEGIpstaLREISLLKELKHPNIVKLLDVIHTENKLYLVF- 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHgDLLRFIRSPQRVSaqcpgwgvsasthlcrcSPvsscpqnPTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd07829     78 EYCDQ-DLKKYLDKRPGPL-----------------PP-------NLIK---SIMYQLLRGLAYCHSHRILHRDLKPQNL 129
                          170       180
                   ....*....|....*....|....*.
gi 2678964124 1260 MLDESFTVKVADFGLAR--GILDKEY 1283
Cdd:cd07829    130 LINRDGVLKLADFGLARafGIPLRTY 155
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
1106-1281 6.00e-15

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: 77.35  E-value: 6.00e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEytdEAQNQIHCAIKslsRITEVQEVEAF----LREGLIMRGLHHPNILALIG-IMLPPEGLPR---- 1176
Cdd:cd07866     16 LGEGTFGEVYKAR---QIKTGRVVALK---KILMHNEKDGFpitaLREIKILKKLKHPNVVPLIDmAVERPDKSKRkrgs 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 --VLLPYMRHgDLLRFIRSPqrvsaqcpgwgvsaSTHLcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDL 1254
Cdd:cd07866     90 vyMVTPYMDH-DLSGLLENP--------------SVKL-------------TESQIKCYMLQLLEGINYLHENHILHRDI 141
                          170       180
                   ....*....|....*....|....*..
gi 2678964124 1255 AARNCMLDESFTVKVADFGLARGILDK 1281
Cdd:cd07866    142 KAANILIDNQGILKIADFGLARPYDGP 168
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
1103-1284 6.02e-15

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: 77.79  E-value: 6.02e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1103 DQVIGKGHFGVVyhGEYTDEAQNQiHCAIKSLSR-ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPR----- 1176
Cdd:cd07855     10 IETIGSGAYGVV--CSAIDTKSGQ-KVAIKKIPNaFDVVTTAKRTLRELKILRHFKHDNIIAIRDILRPKVPYADfkdvy 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 VLLPYMRhGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscpqnPTVKDLISFGL-QVACGMEYLAEQKFVHRDLA 1255
Cdd:cd07855     87 VVLDLME-SDLHHIIHSDQ-----------------------------PLTLEHIRYFLyQLLRGLKYIHSANVIHRDLK 136
                          170       180       190
                   ....*....|....*....|....*....|...
gi 2678964124 1256 ARNCMLDESFTVKVADFGLARGI----LDKEYY 1284
Cdd:cd07855    137 PSNLLVNENCELKIGDFGMARGLctspEEHKYF 169
IPT smart00429
ig-like, plexins, transcription factors;
709-792 7.91e-15

ig-like, plexins, transcription factors;


Pssm-ID: 214657 [Multi-domain]  Cd Length: 90  Bit Score: 70.91  E-value: 7.91e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   709 EPMLTSIKPDFGPRAGGTYLTLEGQSLSVGTSRAVLVNGTQ--CRLEQVSEEKILCVTPPGA-GTASVPLR-LQIGGAEV 784
Cdd:smart00429    1 DPVITRISPTSGPVSGGTEITLCGKNLKSISVVFVEVGVGEapCTFSPSSSTAIVCKTPPYHnIPGSVPVRtVGLRNGGV 80

                    ....*....
gi 2678964124   785 RGSR-TFHY 792
Cdd:smart00429   81 PSSPqPFTY 89
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
1106-1315 1.22e-14

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: 75.34  E-value: 1.22e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQnqiHCAIK--SLSRITEvQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMR 1183
Cdd:cd06627      8 IGRGAFGSVYKGLNLNTGE---FVAIKqiSLEKIPK-SDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSL-YIILEYVE 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRspqrvsaqcpgwgvsasthlcrcsPVSSCPQNptvkdLISFGL-QVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd06627     83 NGSLASIIK------------------------KFGKFPES-----LVAVYIyQVLEGLAYLHEQGVIHRDIKGANILTT 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1263 ESFTVKVADFGLARGI--LDKEYYSVrqhrhARLPvKWMALESLQTYRFTTKSDV 1315
Cdd:cd06627    134 KDGLVKLADFGVATKLneVEKDENSV-----VGTP-YWMAPEVIEMSGVTTASDI 182
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
1105-1315 1.34e-14

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: 75.46  E-value: 1.34e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEaqnqiHCAIKSLSRITE---VQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd14146      1 IIGVGGFGKVYRATWKGQ-----EVAVKAARQDPDediKATAESVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVM-EF 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQrvSAQCPGWGVSASTHLcrcspvsscpqnptvkdLISFGLQVACGMEYLAEQKFV---HRDLAARN 1258
Cdd:cd14146     75 ARGGTLNRALAAAN--AAPGPRRARRIPPHI-----------------LVNWAVQIARGMLYLHEEAVVpilHRDLKSSN 135
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1259 CMLDESF--------TVKVADFGLARgildkeyysvRQHRHARLPV----KWMALESLQTYRFTTKSDV 1315
Cdd:cd14146    136 ILLLEKIehddicnkTLKITDFGLAR----------EWHRTTKMSAagtyAWMAPEVIKSSLFSKGSDI 194
IPT cd00102
Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as ...
710-794 1.92e-14

Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor receptors), as well as, cyclodextrin glycosyltransferase and similar enzymes. Although they are involved in DNA binding in transcription factors, their function in other proteins is unknown. In these transcription factors, IPTs form homo- or heterodimers with the exception of the nuclear factor of activated Tcells (NFAT) transcription factors which are mainly monomers.


Pssm-ID: 238050 [Multi-domain]  Cd Length: 89  Bit Score: 69.80  E-value: 1.92e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  710 PMLTSIKPDFGPRAGGTYLTLEGQSLSVGTSRAVLVNGTQ-CRLEQVSEEKILCVTPPGAGTASVPLRLQIGGAEVRG-- 786
Cdd:cd00102      1 PVITSISPSSGPVSGGTEVTITGSNFGSGSNLRVTFGGGVpCSVLSVSSTAIVCTTPPYANPGPGPVEVTVDRGNGGIts 80

                   ....*....
gi 2678964124  787 -SRTFHYKE 794
Cdd:cd00102     81 sPLTFTYVP 89
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
1104-1276 3.96e-14

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: 74.05  E-value: 3.96e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEytdEAQNQIHCAIKSLS-RITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVlLPYM 1182
Cdd:cd05117      6 KVLGRGSFGVVRLAV---HKKTGEEYAVKIIDkKKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLV-MELC 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVSAQcpgwgvSAStHLCRcspvsscpqnptvkdlisfglQVACGMEYLAEQKFVHRDLAARNCML- 1261
Cdd:cd05117     82 TGGELFDRIVKKGSFSER------EAA-KIMK---------------------QILSAVAYLHSQGIVHRDLKPENILLa 133
                          170
                   ....*....|....*..
gi 2678964124 1262 --DESFTVKVADFGLAR 1276
Cdd:cd05117    134 skDPDSPIKIIDFGLAK 150
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
1105-1315 4.02e-14

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: 73.87  E-value: 4.02e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEaqnqiHCAIKSLSRITEVQ---EVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVlLPY 1181
Cdd:cd14148      1 IIGVGGFGKVYKGLWRGE-----EVAVKAARQDPDEDiavTAENVRQEARLFWMLQHPNIIALRGVCLNPPHLCLV-MEY 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFI---RSPQRVsaqcpgwgvsasthlcrcspvsscpqnptvkdLISFGLQVACGMEYLAEQKFV---HRDLA 1255
Cdd:cd14148     75 ARGGALNRALagkKVPPHV--------------------------------LVNWAVQIARGMNYLHNEAIVpiiHRDLK 122
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1256 ARNCMLDE--------SFTVKVADFGLARgildkEYYSVRQHRHARlPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14148    123 SSNILILEpienddlsGKTLKITDFGLAR-----EWHKTTKMSAAG-TYAWMAPEVIRLSLFSKSSDV 184
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
1106-1315 6.87e-14

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: 73.26  E-value: 6.87e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEaqnQIHCAIKSL-SRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMRH 1184
Cdd:cd13978      1 LGSGGFGTVSKARHVSW---FGMVAIKCLhSSPNCIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVM-EYMEN 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLlrfiRSPQRVSAQCPGWGVSasthlcrcspvsscpqnptvkdlISFGLQVACGMEYL--AEQKFVHRDLAARNCMLD 1262
Cdd:cd13978     77 GSL----KSLLEREIQDVPWSLR-----------------------FRIIHEIALGMNFLhnMDPPLLHHDLKPENILLD 129
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1263 ESFTVKVADFGLARgildkeyYSVRQHRHARLPVK--------WMALESLQT--YRFTTKSDV 1315
Cdd:cd13978    130 NHFHVKISDFGLSK-------LGMKSISANRRRGTenlggtpiYMAPEAFDDfnKKPTSKSDV 185
Sema_plexin_B3 cd11277
The Sema domain, a protein interacting module, of Plexin B3; Plexin B3 is the receptor of ...
65-385 1.64e-13

The Sema domain, a protein interacting module, of Plexin B3; Plexin B3 is the receptor of semaphorin 5A. It is a highly potent stimulator of neurite outgrowth of primary murine cerebellar neurons. Plexin B3 has been linked to verbal performance and white matter volume in human brain. Furthermore, Sema5A and plexin B3 have been implicated in the progression of various types of cancer. They play an important role in the invasion and metastasis of gastric carcinoma. The stimulation of plexin B3 by Sema5A binding in human glioma cells results in the inhibition of cell migration and invasion. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200538 [Multi-domain]  Cd Length: 434  Bit Score: 74.46  E-value: 1.64e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   65 DSKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGD-PGCQTCASCGPGPHGPPND-TDTLVLVMEPGlPALVSCGSTLQG 142
Cdd:cd11277     14 DPGSGTLYVGAVNRLYQLSPDLQLLGEAVTGPVLDsPDCLPFRDPADCPQARLTDnANKLLLVSERA-GELVACGQVRQG 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  143 RC----------FLHELEPQGEALHLAApaclfsasnNKPEACTDCVashlgtrvtVVEQGHASYFYVASSLDPELAASF 212
Cdd:cd11277     93 VCekrrlgnvaqVLYQAEDPGDGQFVAA---------NDPGVATVGL---------VVEAPGRDLLLVGRGLTGKLSAGI 154
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  213 SPrsVSIRRLKSDTSGFQPGFPSLSVlpKYLASYLIKYVHSFHSGDFVYFL-----TVQPMDVRsppsalqTRLVRLNAI 287
Cdd:cd11277    155 PP--LTIRQLAGAQAFSSEGLGKLVV--GDFSDYNNSYVGAFAHNGYVYFLfrrrgARAQAEYR-------TYVARVCLG 223
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  288 EPEIGDYRELVLDCHfapkrrrrsgapkslQAYQVLQAAHSAPvdaklaldlsiseGQEVLFGVFVAVKDSSSGPN--SV 365
Cdd:cd11277    224 DTNLYSYVEVPLVCQ---------------GGYNLAQAAYLAP-------------GQGTLFVVFAAGQGSTPTPTdqTA 275
                          330       340
                   ....*....|....*....|
gi 2678964124  366 VCAFPINHLDNLIEEGVERC 385
Cdd:cd11277    276 LCAYPLVELDSAMERARRLC 295
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
1106-1276 2.22e-13

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: 71.82  E-value: 2.22e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNqihCAIK-----SLSRITEVQEVEAFLREGL--------IMRGLHHPNILALIGIMLPPE 1172
Cdd:cd14008      1 LGRGSFGKVKLALDTETGQL---YAIKifnksRLRKRREGKNDRGKIKNALddvrreiaIMKKLDHPNIVRLYEVIDDPE 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 G--LPRVLlPYMRHGDLLRfIRSPQRVSAQcpgwgvsaSTHLCRCspvsscpqnpTVKDLIsfglqvaCGMEYLAEQKFV 1250
Cdd:cd14008     78 SdkLYLVL-EYCEGGPVME-LDSGDRVPPL--------PEETARK----------YFRDLV-------LGLEYLHENGIV 130
                          170       180
                   ....*....|....*....|....*.
gi 2678964124 1251 HRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd14008    131 HRDIKPENLLLTADGTVKISDFGVSE 156
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
1106-1315 2.40e-13

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: 71.59  E-value: 2.40e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAqnqihcAIKSLsRITE--VQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGlprvllpymr 1183
Cdd:cd14150      8 IGTGSFGTVFRGKWHGDV------AVKIL-KVTEptPEQLQAFKNEMQVLRKTRHVNILLFMGFMTRPNF---------- 70
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 hgdllrfirspQRVSAQCPGWGVSASTHLCRcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd14150     71 -----------AIITQWCEGSSLYRHLHVTE--------TRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHE 131
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1264 SFTVKVADFGLArgILDKEYYSVRQHRHARLPVKWMALESLQ---TYRFTTKSDV 1315
Cdd:cd14150    132 GLTVKIGDFGLA--TVKTRWSGSQQVEQPSGSILWMAPEVIRmqdTNPYSFQSDV 184
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
1147-1315 2.50e-13

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: 71.35  E-value: 2.50e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1147 LREGLIMRGLHHPNILALIGIMLPpEGLPRVLLPYMRHGDLLRFIRSPQRVSAqcpgwgvsasthlcrcspvsscpqnpT 1226
Cdd:cd14155     36 LREVQLMNRLSHPNILRFMGVCVH-QGQLHALTEYINGGNLEQLLDSNEPLSW--------------------------T 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1227 VKdlISFGLQVACGMEYLAEQKFVHRDLAARNCML---DESFTVKVADFGLARGILDKEYysvrqhRHARLPV----KWM 1299
Cdd:cd14155     89 VR--VKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrdENGYTAVVGDFGLAEKIPDYSD------GKEKLAVvgspYWM 160
                          170
                   ....*....|....*.
gi 2678964124 1300 ALESLQTYRFTTKSDV 1315
Cdd:cd14155    161 APEVLRGEPYNEKADV 176
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
1106-1315 2.82e-13

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: 71.41  E-value: 2.82e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIhCAIKSLSRIT--EVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMR 1183
Cdd:cd14064      1 IGSGSFGKVYKGRC----RNKI-VAIKRYRANTycSKSDVDMFCREVSILCRLNHPCVIQFVGACLDDPSQFAIVTQYVS 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISfgLQVACGMEYLAE--QKFVHRDLAARNCML 1261
Cdd:cd14064     76 GGSLFSLLHEQKRV-------------------------IDLQSKLIIA--VDVAKGMEYLHNltQPIIHRDLNSHNILL 128
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1262 DESFTVKVADFGLARGIldkeyYSVRQHRHARLP--VKWMALESL-QTYRFTTKSDV 1315
Cdd:cd14064    129 YEDGHAVVADFGESRFL-----QSLDEDNMTKQPgnLRWMAPEVFtQCTRYSIKADV 180
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
1105-1295 4.39e-13

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: 70.73  E-value: 4.39e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEAQnqiHCAIKSLSRITEVQEveAFLREGLIMRGL----HHPNILALIGIMLPPEGLPRVL-L 1179
Cdd:cd05118      6 KIGEGAFGTVWLARDKVTGE---KVAIKKIKNDFRHPK--AALREIKLLKHLndveGHPNIVKLLDVFEHRGGNHLCLvF 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMrHGDLLRFIRSPQRvsaqcpgwgvsasthlcrcspvssCPQNPTVKDLIsfgLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd05118     81 ELM-GMNLYELIKDYPR------------------------GLPLDLIKSYL---YQLLQALDFLHSNGIIHRDLKPENI 132
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 2678964124 1260 MLD-ESFTVKVADFGLARGILDKEYYSVRQHRHARLP 1295
Cdd:cd05118    133 LINlELGQLKLADFGLARSFTSPPYTPYVATRWYRAP 169
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
1104-1275 6.24e-13

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: 70.20  E-value: 6.24e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEytdEAQNQIHCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIG-------IMLppegl 1174
Cdd:cd14007      6 KPLGKGKFGNVYLAR---EKKSGFIVALKVISKsqLQKSGLEHQLRREIEIQSHLRHPNILRLYGyfedkkrIYL----- 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1175 prvLLPYMRHGDLlrfirspqrvsaqcpgwgvsaSTHLCRCSPVSscpqNPTVKDLIsfgLQVACGMEYLAEQKFVHRDL 1254
Cdd:cd14007     78 ---ILEYAPNGEL---------------------YKELKKQKRFD----EKEAAKYI---YQLALALDYLHSKNIIHRDI 126
                          170       180
                   ....*....|....*....|.
gi 2678964124 1255 AARNCMLDESFTVKVADFGLA 1275
Cdd:cd14007    127 KPENILLGSNGELKLADFGWS 147
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
1105-1277 7.49e-13

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: 70.02  E-value: 7.49e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTdeaQNQIHCAIKSLSRITEVQEV-EAFL-REGLIMRGLHHPNILALIGIMlppEGLPRV--LLP 1180
Cdd:cd14162      7 TLGHGSYAVVKKAYST---KHKCKVAIKIVSKKKAPEDYlQKFLpREIEVIKGLKHPNLICFYEAI---ETTSRVyiIME 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVSAQcpgwgvSASTHLCrcspvsscpqnptvkdlisfglQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd14162     81 LAENGDLLDYIRKNGALPEP------QARRWFR----------------------QLVAGVEYCHSKGVVHRDLKCENLL 132
                          170
                   ....*....|....*..
gi 2678964124 1261 LDESFTVKVADFGLARG 1277
Cdd:cd14162    133 LDKNNNLKITDFGFARG 149
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
1090-1315 8.02e-13

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: 70.48  E-value: 8.02e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1090 DVLIPHEQVVIhtDQVIGKGHFGVVYHGEYTDEAqnqihcAIKSLSRITEV-QEVEAFLREGLIMRGLHHPNILALIGIM 1168
Cdd:cd14151      2 DWEIPDGQITV--GQRIGSGSFGTVYKGKWHGDV------AVKMLNVTAPTpQQLQAFKNEVGVLRKTRHVNILLFMGYS 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1169 LPPEglprvllpymrhgdllrfirsPQRVSAQCPGWGVSASTHLCRcspvsscpQNPTVKDLISFGLQVACGMEYLAEQK 1248
Cdd:cd14151     74 TKPQ---------------------LAIVTQWCEGSSLYHHLHIIE--------TKFEMIKLIDIARQTAQGMDYLHAKS 124
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1249 FVHRDLAARNCMLDESFTVKVADFGLArgILDKEYYSVRQHRHARLPVKWMALESLQ---TYRFTTKSDV 1315
Cdd:cd14151    125 IIHRDLKSNNIFLHEDLTVKIGDFGLA--TVKSRWSGSHQFEQLSGSILWMAPEVIRmqdKNPYSFQSDV 192
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
1104-1276 1.57e-12

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: 69.03  E-value: 1.57e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgEYTDEAQNQIhCAIK--SLSRITEvQEVEAFLREGLIMRGLHHPNILA----------LIGIMlpp 1171
Cdd:cd08215      6 RVIGKGSFGSAY--LVRRKSDGKL-YVLKeiDLSNMSE-KEREEALNEVKLLSKLKHPNIVKyyesfeengkLCIVM--- 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1172 EglprvllpYMRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVH 1251
Cdd:cd08215     79 E--------YADGGDLAQKIKKQKKKG------------------------QPFPEEQILDWFVQICLALKYLHSRKILH 126
                          170       180
                   ....*....|....*....|....*
gi 2678964124 1252 RDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd08215    127 RDLKTQNIFLTKDGVVKLGDFGISK 151
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
1103-1315 4.96e-12

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: 67.76  E-value: 4.96e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1103 DQVIGKGHFGVVYHGEYtdeaqNQIHCAIKSLSRITE---VQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLl 1179
Cdd:cd14145     11 EEIIGIGGFGKVYRAIW-----IGDEVAVKAARHDPDediSQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVM- 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIrSPQRVSaqcpgwgvsasthlcrcspvsscpqnPTVkdLISFGLQVACGMEYLAEQKFV---HRDLAA 1256
Cdd:cd14145     85 EFARGGPLNRVL-SGKRIP--------------------------PDI--LVNWAVQIARGMNYLHCEAIVpviHRDLKS 135
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1257 RNCMLDESF--------TVKVADFGLARgildkeyysvRQHRHARLPV----KWMALESLQTYRFTTKSDV 1315
Cdd:cd14145    136 SNILILEKVengdlsnkILKITDFGLAR----------EWHRTTKMSAagtyAWMAPEVIRSSMFSKGSDV 196
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
1106-1315 5.05e-12

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: 68.13  E-value: 5.05e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAqnqihcAIKSLSRITEVQE-VEAFLREGLIMRGLHHPNILALIGimlppeglprvllpYMRH 1184
Cdd:cd14149     20 IGSGSFGTVYKGKWHGDV------AVKILKVVDPTPEqFQAFRNEVAVLRKTRHVNILLFMG--------------YMTK 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLlrfirspQRVSAQCPGWGVSASTHLCRcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd14149     80 DNL-------AIVTQWCEGSSLYKHLHVQE--------TKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEG 144
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1265 FTVKVADFGLArgILDKEYYSVRQHRHARLPVKWMALESLQTYR---FTTKSDV 1315
Cdd:cd14149    145 LTVKIGDFGLA--TVKSRWSGSQQVEQPTGSILWMAPEVIRMQDnnpFSFQSDV 196
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
1104-1290 5.11e-12

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: 67.94  E-value: 5.11e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEaqNQIhCAIK-------SLSRITEVQEVEAflreglIMRGLHHPNILALIGIMLPPEGLPR 1176
Cdd:cd07830      5 KQLGDGTFGSVYLARNKET--GEL-VAIKkmkkkfySWEECMNLREVKS------LRKLNEHPNIVKLKEVFRENDELYF 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 VLlPYMrHGDLLRFIRSPQRvsaqcpgwgvsasthlcrcSPVSscpqNPTVKDLIsfgLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd07830     76 VF-EYM-EGNLYQLMKDRKG-------------------KPFS----ESVIRSII---YQILQGLAHIHKHGFFHRDLKP 127
                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 2678964124 1257 RNCMLDESFTVKVADFGLARGILDK----EYYSVRQHR 1290
Cdd:cd07830    128 ENLLVSGPEVVKIADFGLAREIRSRppytDYVSTRWYR 165
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
1104-1315 8.71e-12

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: 67.00  E-value: 8.71e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDeaqNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMR 1183
Cdd:cd06610      7 EVIGSGATAVVYAAYCLP---KKEKVAIKRIDLEKCQTSMDELRKEIQAMSQCNHPNVVSYYTSFVVGDEL-WLVMPLLS 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSpqrvsaqcpgwgvsasthlcrcspvsSCPQNPTVKDLISFGL-QVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd06610     83 GGSLLDIMKS--------------------------SYPRGGLDEAIIATVLkEVLKGLEYLHSNGQIHRDVKAGNILLG 136
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1263 ESFTVKVADFGLARGILDkeyYSVRQHRhARLPVK----WMALESLQTYR-FTTKSDV 1315
Cdd:cd06610    137 EDGSVKIADFGVSASLAT---GGDRTRK-VRKTFVgtpcWMAPEVMEQVRgYDFKADI 190
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
1106-1315 1.15e-11

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: 67.14  E-value: 1.15e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEaqnqiHCAIKSL---SRITEVQEVEAFLREGLIMRGLHHPNILALIGIML--PPeglPRVLLP 1180
Cdd:cd14158     23 LGEGGFGVVFKGYINDK-----NVAVKKLaamVDISTEDLTKQFEQEIQVMAKCQHENLVELLGYSCdgPQ---LCLVYT 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLrfirspQRVSaqCPGWGVSASTHLcRCSpvsscpqnptvkdlISFGlqVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd14158     95 YMPNGSLL------DRLA--CLNDTPPLSWHM-RCK--------------IAQG--TANGINYLHENNHIHRDIKSANIL 149
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1261 LDESFTVKVADFGLARGilDKEYYSVRQHRHARLPVKWMALESLQtYRFTTKSDV 1315
Cdd:cd14158    150 LDETFVPKISDFGLARA--SEKFSQTIMTERIVGTTAYMAPEALR-GEITPKSDI 201
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
1106-1315 1.17e-11

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: 66.75  E-value: 1.17e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDeaqNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIG-IMLPPEGLprVLLPYMRH 1184
Cdd:cd14664      1 IGRGGAGTVYKGVMPN---GTL-VAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGyCSNPTTNL--LVYEYMPN 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVKDLISfgLQVACGMEYLAEQ---KFVHRDLAARNCML 1261
Cdd:cd14664     75 GSLGELLHS----------------------RPESQPPLDWETRQRIA--LGSARGLAYLHHDcspLIIHRDVKSNNILL 130
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1262 DESFTVKVADFGLARGILDKEYYSVRQHRHArlpVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14664    131 DEEFEAHVADFGLAKLMDDKDSHVMSSVAGS---YGYIAPEYAYTGKVSEKSDV 181
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
1106-1275 1.57e-11

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: 66.18  E-value: 1.57e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIHcAIKSLSR--ITEVQE--VEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPY 1181
Cdd:cd13994      1 IGKGATSVVRIVTKKNPRSGVLY-AVKEYRRrdDESKRKdyVKRLTSEYIISSKLHHPNIVKVLDLCQDLHGKWCLVMEY 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSAQ---CpgwgvsasthlcrcspvsscpqnptvkdlisFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd13994     80 CPGGDLFTLIEKADSLSLEekdC-------------------------------FFKQILRGVAYLHSHGIAHRDLKPEN 128
                          170
                   ....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLA 1275
Cdd:cd13994    129 ILLDEDGVLKLTDFGTA 145
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
1106-1315 2.00e-11

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: 65.88  E-value: 2.00e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaqnqiH--CAIKSL--SRITEVQeVEAFLREGLIMRGLHHPNILALIGIMLPPEglprvllpy 1181
Cdd:cd14062      1 IGSGSFGTVYKGRW--------HgdVAVKKLnvTDPTPSQ-LQAFKNEVAVLRKTRHVNILLFMGYMTKPQ--------- 62
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 mrhgdlLRFirspqrVSAQCPGwgvsasthlcrcspvSSCPQNPTVKD-------LISFGLQVACGMEYLAEQKFVHRDL 1254
Cdd:cd14062     63 ------LAI------VTQWCEG---------------SSLYKHLHVLEtkfemlqLIDIARQTAQGMDYLHAKNIIHRDL 115
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1255 AARNCMLDESFTVKVADFGLArgILDKEYYSVRQHRHARLPVKWMALESLQTYR---FTTKSDV 1315
Cdd:cd14062    116 KSNNIFLHEDLTVKIGDFGLA--TVKTRWSGSQQFEQPTGSILWMAPEVIRMQDenpYSFQSDV 177
IPT smart00429
ig-like, plexins, transcription factors;
594-651 2.87e-11

ig-like, plexins, transcription factors;


Pssm-ID: 214657 [Multi-domain]  Cd Length: 90  Bit Score: 60.90  E-value: 2.87e-11
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124   594 PPEITEFHPHSGPLRGTTRLTLCGSNFylrpdGVVPEGTHQITVGQSPCRLLPKDSST 651
Cdd:smart00429    1 DPVITRISPTSGPVSGGTEITLCGKNL-----KSISVVFVEVGVGEAPCTFSPSSSTA 53
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1101-1280 3.00e-11

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: 65.36  E-value: 3.00e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1101 HTDQVIGKGHFGVVYHGEYTDEAQnqiHCAIKSLS-RITEVQEVEAFLREGLIMRGLHHPNILALIGiMLPPEGLPRVLL 1179
Cdd:cd08225      3 EIIKKIGEGSFGKIYLAKAKSDSE---HCVIKEIDlTKMPVKEKEASKKEVILLAKMKHPNIVTFFA-SFQENGRLFIVM 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLrfirspQRVSAQcpgWGVSASThlcrcspvsscpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd08225     79 EYCDGGDLM------KRINRQ---RGVLFSE-----------------DQILSWFVQISLGLKHIHDRKILHRDIKSQNI 132
                          170       180
                   ....*....|....*....|..
gi 2678964124 1260 MLDESFTV-KVADFGLARGILD 1280
Cdd:cd08225    133 FLSKNGMVaKLGDFGIARQLND 154
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
1106-1276 3.82e-11

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: 65.67  E-value: 3.82e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEaqNQIhCAIKS--LSRITEVQEVEAF--LREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd07841      8 LGEGTYAVVYKARDKET--GRI-VAIKKikLGERKEAKDGINFtaLREIKLLQELKHPNIIGLLDVFGHKSNINLVF-EF 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MrHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd07841     84 M-ETDLEKVIKDKSIVL---------------------------TPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLI 135
                          170
                   ....*....|....*
gi 2678964124 1262 DESFTVKVADFGLAR 1276
Cdd:cd07841    136 ASDGVLKLADFGLAR 150
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
1144-1315 3.95e-11

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: 65.21  E-value: 3.95e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1144 EAFLREGLIMRGLHHPNILALIGIMLPpEGLPRVLLPYMRHGDLLRFIrspQRVSAqcpgwgvsasthlcrcsPVSscpq 1223
Cdd:cd14027     36 EALLEEGKMMNRLRHSRVVKLLGVILE-EGKYSLVMEYMEKGNLMHVL---KKVSV-----------------PLS---- 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1224 nptVKDliSFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR----GILDKEyYSVRQHR------HAR 1293
Cdd:cd14027     91 ---VKG--RIILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASfkmwSKLTKE-EHNEQREvdgtakKNA 164
                          170       180
                   ....*....|....*....|....
gi 2678964124 1294 LPVKWMALESLQTY--RFTTKSDV 1315
Cdd:cd14027    165 GTLYYMAPEHLNDVnaKPTEKSDV 188
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
1104-1276 4.31e-11

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: 65.31  E-value: 4.31e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGeyTDEAQNQIHcAIKSLSRITEVQE--VEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd05581      7 KPLGEGSYSTVVLA--KEKETGKEY-AIKVLDKRHIIKEkkVKYVTIEKEVLSRLAHPGIVKLYYTFQDESKLYFVL-EY 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSAQCpgwgvsasthlcrcspvsscpqnptvkdlISFGL-QVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05581     83 APNGDLLEYIRKYGSLDEKC-----------------------------TRFYTaEIVLALEYLHSKGIIHRDLKPENIL 133
                          170
                   ....*....|....*.
gi 2678964124 1261 LDESFTVKVADFGLAR 1276
Cdd:cd05581    134 LDEDMHIKITDFGTAK 149
Sema_plexin_B1 cd11275
The Sema domain, a protein interacting module, of Plexin B1; Plexin B1 serves as the ...
65-385 4.54e-11

The Sema domain, a protein interacting module, of Plexin B1; Plexin B1 serves as the Semaphorin 4D receptor and functions as a regulator of developing neurons and a tumor suppressor protein for melanoma. The Sema4D-plexin B signaling complex regulates dendritic and axonal complexity. The activation of Plexin B1 by Sema4D produces an acute collapse of axonal growth cones in hippocampal and retinal neurons over the early stages of neurite outgrowth and promotes branching and complexity. As a tumor suppressor, plexin B1 abrogates activation of the oncogenic receptor, c-Met, by its ligand, hepatocyte growth factor (HGF), in melanoma. Furthermore, plexin B1 suppresses integrin-dependent migration and activation of pp125FAK and inhibits Rho activity. Plexin B1 is highly expressed in endothelial cells and its activation by Sema4D elicits a potent proangiogenic response. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.


Pssm-ID: 200536 [Multi-domain]  Cd Length: 461  Bit Score: 66.91  E-value: 4.54e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124   65 DSKNSAVFVAIRNRLHVLGPDLQYIESLTTGPIGDP-GCQTCASCGPGPHGPPNDTDTLVLVMEPGLPALVSCGSTLQGR 143
Cdd:cd11275     14 DPESGTLYLGATNFLFQLTPDLLLENMVQTGPVLDSkDCLPPVSKLECPQAQHTNNHNKLLLVNPVQKELIVCGSVHQGI 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  144 C----------FLHELEPQGEALHLAApaclfsasnNKPEACT-DCVA-SHLGTRVTVVEQGHASYfYVASSLDPELAAS 211
Cdd:cd11275     94 CekrrlgsidhVLFRPERPGDTQYVAA---------NDPNVTTvGLVAySKDGVPLLFVGRGYTSR-GVGGGIPPITTRN 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  212 FSPRSVSIRRLKS-----DTSGFQPGfpslsvlpkYLASYLIKYVHSFHSGDFVYFLTVQpMDVRSPPSALQTRLVRLNA 286
Cdd:cd11275    164 LRAHGDDATDSHSifsyeETAKLAVG---------RLSEYNHHFIKAFTYGSSVYFLFYR-RDLKSQSREYKTYISRICL 233
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  287 IEPEIGDYRELVLDCHFAPKRrrrsgapkslqaYQVLQAAHSAPVDAKLALDLSISEGqEVLFGVFVAVKDSSS--GPNS 364
Cdd:cd11275    234 DDSHYYSYVELPLLCQSKANT------------YSLLQAAYVTQPGERLAQGQLDTDG-EVLFAAFSAWQASSGklSEES 300
                          330       340
                   ....*....|....*....|.
gi 2678964124  365 VVCAFPINHLDNLIEEGVERC 385
Cdd:cd11275    301 ALCAYPMDEVDRLTNWTRDVC 321
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
1104-1275 6.38e-11

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: 64.21  E-value: 6.38e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEytdEAQNQIhCAIKSL--SRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPrVLLPY 1181
Cdd:cd14161      9 ETLGKGTYGRVKKAR---DSSGRL-VAIKSIrkDRIKDEQDLLHIRREIEIMSSLNHPHIISVYEVFENSSKIV-IVMEY 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSAQcpgwgvsASTHLCRcspvsscpqnptvkdlisfglQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd14161     84 ASRGDLYDYISERQRLSEL-------EARHFFR---------------------QIVSAVHYCHANGIVHRDLKLENILL 135
                          170
                   ....*....|....
gi 2678964124 1262 DESFTVKVADFGLA 1275
Cdd:cd14161    136 DANGNIKIADFGLS 149
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
1106-1283 6.61e-11

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: 64.21  E-value: 6.61e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNqihCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMR 1183
Cdd:cd14079     10 LGVGSFGKVKLAEHELTGHK---VAVKILNRqkIKSLDMEEKIRREIQILKLFRHPHIIRLYEVIETPTDIFMVM-EYVS 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQRVSAqcpgwgvsasthlcrcspvsscpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd14079     86 GGELFDYIVQKGRLSE----------------------------DEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDS 137
                          170       180
                   ....*....|....*....|
gi 2678964124 1264 SFTVKVADFGLARGILDKEY 1283
Cdd:cd14079    138 NMNVKIADFGLSNIMRDGEF 157
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
1100-1283 7.74e-11

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: 63.97  E-value: 7.74e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEYTdeaQNQIHCAIKSLSRITEVQEVEAFLR-EGLIMRGLHHPNILALIGIMLPPEglpRVL 1178
Cdd:cd14082      5 IFPDEVLGSGQFGIVYGGKHR---KTGRDVAIKVIDKLRFPTKQESQLRnEVAILQQLSHPGVVNLECMFETPE---RVF 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMR-HGDLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTvKDLISfglQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd14082     79 VVMEKlHGDMLEMILS----------------------SEKGRLPERIT-KFLVT---QILVALRYLHSKNIVHCDLKPE 132
                          170       180
                   ....*....|....*....|....*....
gi 2678964124 1258 NCML--DESF-TVKVADFGLARGILDKEY 1283
Cdd:cd14082    133 NVLLasAEPFpQVKLCDFGFARIIGEKSF 161
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
1106-1283 8.15e-11

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: 63.83  E-value: 8.15e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeytDEAQNQIHCAIKSLSRITEVQEveAFLREGLIMRGLHHPNILALIGIMLPPEGLprVL-LPYMRH 1184
Cdd:cd14006      1 LGRGRFGVVKRC---IEKATGREFAAKFIPKRDKKKE--AVLREISILNQLQHPRIIQLHEAYESPTEL--VLiLELCSG 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSPQRVSAQCpgwgvsasthlcrcspvsscpqnptVKDLISfglQVACGMEYLAEQKFVHRDLAARNCMLDE- 1263
Cdd:cd14006     74 GELLDRLAERGSLSEEE-------------------------VRTYMR---QLLEGLQYLHNHHILHLDLKPENILLADr 125
                          170       180
                   ....*....|....*....|.
gi 2678964124 1264 -SFTVKVADFGLARGILDKEY 1283
Cdd:cd14006    126 pSPQIKIIDFGLARKLNPGEE 146
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
1106-1275 1.18e-10

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: 63.73  E-value: 1.18e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgEYTDEAQNQIHcAIK--SLSRITEVQEVEAFLREGLIMRGLHHPNILALIG---------Imlppegl 1174
Cdd:cd14099      9 LGKGGFAKCY--EVTDMSTGKVY-AGKvvPKSSLTKPKQREKLKSEIKIHRSLKHPNIVKFHDcfedeenvyI------- 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1175 prvLLPYMRHGDLLRFIRSPQRVS---AQCpgwgvsasthlcrcspvsscpqnptvkdlisFGLQVACGMEYLAEQKFVH 1251
Cdd:cd14099     79 ---LLELCSNGSLMELLKRRKALTepeVRY-------------------------------FMRQILSGVKYLHSNRIIH 124
                          170       180
                   ....*....|....*....|....
gi 2678964124 1252 RDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14099    125 RDLKLGNLFLDENMNVKIGDFGLA 148
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
1105-1278 1.27e-10

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: 63.65  E-value: 1.27e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEAQNQihcAIKSLSR---ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVlLPY 1181
Cdd:cd14098      7 RLGSGTFAEVKKAVEVETGKMR---AIKQIVKrkvAGNDKNLQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLV-MEY 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSpqrvsaqcpgWGVSASTHlcrCSPVSScpqnptvkdlisfglQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd14098     83 VEGGDLMDFIMA----------WGAIPEQH---ARELTK---------------QILEAMAYTHSMGITHRDLKPENILI 134
                          170
                   ....*....|....*....
gi 2678964124 1262 --DESFTVKVADFGLARGI 1278
Cdd:cd14098    135 tqDDPVIVKISDFGLAKVI 153
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
1106-1276 1.52e-10

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: 64.23  E-value: 1.52e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIHcAIK------------SLSRITEVqeveAFLREglimrgLHHPNILALIGIML-PPE 1172
Cdd:cd07842      8 IGRGTYGRVYKAKRKNGKDGKEY-AIKkfkgdkeqytgiSQSACREI----ALLRE------LKHENVVSLVEVFLeHAD 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 GLPRVLLPYMRHgDLLRFI---RSPQRVSAQcpgwgvsasthlcrcspvsscpqNPTVKDLIsfgLQVACGMEYLAEQKF 1249
Cdd:cd07842     77 KSVYLLFDYAEH-DLWQIIkfhRQAKRVSIP-----------------------PSMVKSLL---WQILNGIHYLHSNWV 129
                          170       180       190
                   ....*....|....*....|....*....|.
gi 2678964124 1250 VHRDLAARNCML----DESFTVKVADFGLAR 1276
Cdd:cd07842    130 LHRDLKPANILVmgegPERGVVKIGDLGLAR 160
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
1106-1294 1.54e-10

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: 64.31  E-value: 1.54e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeyTDEAQNQiHCAIKSLSRITE-VQEVEAFLREGLIMRGLHHPNILALIGIMLPP--EGLPRVLLPY- 1181
Cdd:cd07858     13 IGRGAYGIVCSA--KNSETNE-KVAIKKIANAFDnRIDAKRTLREIKLLRHLDHENVIAIKDIMPPPhrEAFNDVYIVYe 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSaqcpgwgvsaSTHlCRcspvsscpqnptvkdliSFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd07858     90 LMDTDLHQIIRSSQTLS----------DDH-CQ-----------------YFLYQLLRGLKYIHSANVLHRDLKPSNLLL 141
                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 2678964124 1262 DESFTVKVADFGLARGILDK-----EYYSVRQHRHARL 1294
Cdd:cd07858    142 NANCDLKICDFGLARTTSEKgdfmtEYVVTRWYRAPEL 179
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
1105-1315 2.27e-10

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: 62.75  E-value: 2.27e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEAqnqihcAIKSL--SRITEVQeVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPrVLLPYM 1182
Cdd:cd14063      7 VIGKGRFGRVHRGRWHGDV------AIKLLniDYLNEEQ-LEAFKEEVAAYKNTRHDNLVLFMGACMDPPHLA-IVTSLC 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvSSCPQNPTVkdliSFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd14063     79 KGRTLYSLIHERK-----------------------EKFDFNKTV----QIAQQICQGMGYLHAKGIIHKDLKSKNIFLE 131
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1263 ESFTVkVADFGLArGILDKEYYSVRQHRhARLPVKW---MALESLQTYR----------FTTKSDV 1315
Cdd:cd14063    132 NGRVV-ITDFGLF-SLSGLLQPGRREDT-LVIPNGWlcyLAPEIIRALSpdldfeeslpFTKASDV 194
IPT_PCSR cd00603
IPT domain of Plexins and Cell Surface Receptors (PCSR) and related proteins . This subgroup ...
595-651 2.83e-10

IPT domain of Plexins and Cell Surface Receptors (PCSR) and related proteins . This subgroup contains IPT domains of plexins, receptors, like the plasminogen-related growth factor receptors, the hepatocyte growth factor-scatter factors, and the macrophage-stimulating receptors and of fibrocystin. Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT_PCSR domain present preceeded by SEMA (semaphorin) and PSI (plexin, semaphorin, integrin) domains.


Pssm-ID: 238337 [Multi-domain]  Cd Length: 90  Bit Score: 58.23  E-value: 2.83e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124  595 PEITEFHPHSGPLRGTTRLTLCGSNFYLRPdgvvpeGTHQITVGQSPCRLLPKDSST 651
Cdd:cd00603      1 PVITSISPSSGPLSGGTRLTITGSNLGSGS------PRVRVTVGGVPCKVLNVSSTE 51
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
1104-1275 2.85e-10

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: 62.65  E-value: 2.85e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGeyTDEAQNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMR 1183
Cdd:cd06609      7 ERIGKGSFGEVYKG--IDKRTNQV-VAIKVIDLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLKGSKL-WIIMEYCG 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HG---DLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpqnptvkdlISFGL-QVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd06609     83 GGsvlDLLKPGPLDETY---------------------------------IAFILrEVLLGLEYLHSEGKIHRDIKAANI 129
                          170
                   ....*....|....*.
gi 2678964124 1260 MLDESFTVKVADFGLA 1275
Cdd:cd06609    130 LLSEEGDVKLADFGVS 145
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
1104-1282 3.37e-10

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: 62.31  E-value: 3.37e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEY----TDEAQNQIHCAIKSLSRITEVQEVEAflregliMRGLHHPNI-------LALIGIMLPPE 1172
Cdd:cd13996     12 ELLGSGGFGSVYKVRNkvdgVTYAIKKIRLTEKSSASEKVLREVKA-------LAKLNHPNIvryytawVEEPPLYIQME 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 glprvllpYMRHGDLLRFIRspqrvsaqcpgwgvsasthlCRCSpvSSCPQNPTVKDLIsfgLQVACGMEYLAEQKFVHR 1252
Cdd:cd13996     85 --------LCEGGTLRDWID--------------------RRNS--SSKNDRKLALELF---KQILKGVSYIHSKGIVHR 131
                          170       180       190
                   ....*....|....*....|....*....|.
gi 2678964124 1253 DLAARNCMLD-ESFTVKVADFGLARGILDKE 1282
Cdd:cd13996    132 DLKPSNIFLDnDDLQVKIGDFGLATSIGNQK 162
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
1104-1315 3.75e-10

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: 62.40  E-value: 3.75e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHG--EYTDE--AQNQIHCAIKSLSRITEVQE--VEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRV 1177
Cdd:cd06629      7 ELIGKGTYGRVYLAmnATTGEmlAVKQVELPKTSSDRADSRQKtvVDALKSEIDTLKDLDHPNIVQYLGFEETEDYF-SI 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptvKDLI-SFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd06629     86 FLEYVPGGSIGSCLRKYGKFE-----------------------------EDLVrFFTRQILDGLAYLHSKGILHRDLKA 136
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1257 RNCMLDESFTVKVADFGLARGilDKEYYSVRQHRHARLPVKWMALESLQTYR--FTTKSDV 1315
Cdd:cd06629    137 DNILVDLEGICKISDFGISKK--SDDIYGNNGATSMQGSVFWMAPEVIHSQGqgYSAKVDI 195
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
1105-1315 3.80e-10

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: 62.17  E-value: 3.80e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHG--EYTDE--AQNQIHC-AIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLL 1179
Cdd:cd06628      7 LIGSGSFGSVYLGmnASSGElmAVKQVELpSVSAENKDRKKSMLDALQREIALLRELQHENIVQYLGSSSDANHL-NIFL 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMrhgdllrfirspqrvsaqcPGWGVSAsthlcRCSPVSSCPQnPTVKDLISfglQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd06628     86 EYV-------------------PGGSVAT-----LLNNYGAFEE-SLVRNFVR---QILKGLNYLHNRGIIHRDIKGANI 137
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1260 MLDESFTVKVADFGLARGI-LDKEYYSVRQHRHA-RLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd06628    138 LVDNKGGIKISDFGISKKLeANSLSTKNNGARPSlQGSVFWMAPEVVKQTSYTRKADI 195
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
1103-1315 5.19e-10

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: 61.97  E-value: 5.19e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1103 DQVIGKGHFGVVYHGEYTDEAqnqihCAIKSlSRITEVQEV----EAFLREGLIMRGLHHPNILALIGIMLPPEGLPrVL 1178
Cdd:cd14147      8 EEVIGIGGFGKVYRGSWRGEL-----VAVKA-ARQDPDEDIsvtaESVRQEARLFAMLAHPNIIALKAVCLEEPNLC-LV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMRHGDLLRFI---RSPQRVsaqcpgwgvsasthlcrcspvsscpqnptvkdLISFGLQVACGMEYLAEQKFV---HR 1252
Cdd:cd14147     81 MEYAAGGPLSRALagrRVPPHV--------------------------------LVNWAVQIARGMHYLHCEALVpviHR 128
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1253 DLAARN----------CMldESFTVKVADFGLARgildkEYYSVRQHRHARlPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14147    129 DLKSNNilllqpiendDM--EHKTLKITDFGLAR-----EWHKTTQMSAAG-TYAWMAPEVIKASTFSKGSDV 193
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
1106-1276 6.11e-10

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: 61.91  E-value: 6.11e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeyTDEAQNQIhCAIKSLSRITEVQEVEAF-LREGLIMRGL---HHPNILALIGIMLPPEgLPRVLLPY 1181
Cdd:cd07838      7 IGEGAYGTVYKA--RDLQDGRF-VALKKVRVPLSEEGIPLStIREIALLKQLesfEHPNVVRLLDVCHGPR-TDRELKLT 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MR----HGDLLRFIRspqrvsaQCPGWGVSAsthlcrcspvsscpqnPTVKDLISfglQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd07838     83 LVfehvDQDLATYLD-------KCPKPGLPP----------------ETIKDLMR---QLLRGLDFLHSHRIVHRDLKPQ 136
                          170
                   ....*....|....*....
gi 2678964124 1258 NCMLDESFTVKVADFGLAR 1276
Cdd:cd07838    137 NILVTSDGQVKLADFGLAR 155
Pkinase pfam00069
Protein kinase domain;
1101-1192 6.20e-10

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 60.72  E-value: 6.20e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1101 HTDQVIGKGHFGVVYHGeyTDEAQNQIHcAIKSL--SRITEVQEvEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVL 1178
Cdd:pfam00069    2 EVLRKLGSGSFGTVYKA--KHRDTGKIV-AIKKIkkEKIKKKKD-KNILREIKILKKLNHPNIVRLYDAFEDKDNL-YLV 76
                           90
                   ....*....|....
gi 2678964124 1179 LPYMRHGDLLRFIR 1192
Cdd:pfam00069   77 LEYVEGGSLFDLLS 90
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
1104-1315 6.39e-10

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: 61.46  E-value: 6.39e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGeyTDEAQNQiHCAIKSLsRITEvQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMR 1183
Cdd:cd06614      6 EKIGEGASGEVYKA--TDRATGK-EVAIKKM-RLRK-QNKELIINEILIMKECKHPNIVDYYDSYLVGDEL-WVVMEYMD 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLlrfirspqrvsaqcpgwgvsasTHLCRCSPVS-SCPQnptvkdlISF-GLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd06614     80 GGSL----------------------TDIITQNPVRmNESQ-------IAYvCREVLQGLEYLHSQNVIHRDIKSDNILL 130
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1262 DESFTVKVADFGLArGILDKEyysvRQHRHARL--PVkWMALESLQTYRFTTKSDV 1315
Cdd:cd06614    131 SKDGSVKLADFGFA-AQLTKE----KSKRNSVVgtPY-WMAPEVIKRKDYGPKVDI 180
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
1106-1279 8.20e-10

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: 60.95  E-value: 8.20e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVyHGEYTDEAQNQihCAIKSLSRITEVQE-VEAFL-REGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMR 1183
Cdd:cd14165      9 LGEGSYAKV-KSAYSERLKCN--VAIKIIDKKKAPDDfVEKFLpRELEILARLNHKSIIKTYEIFETSDGKVYIVMELGV 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRS----PQRVsAQCPGWgvsasthlcrcspvsscpqnptvkdlisfglQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd14165     86 QGDLLEFIKLrgalPEDV-ARKMFH-------------------------------QLSSAIKYCHELDIVHRDLKCENL 133
                          170       180
                   ....*....|....*....|
gi 2678964124 1260 MLDESFTVKVADFGLARGIL 1279
Cdd:cd14165    134 LLDKDFNIKLTDFGFSKRCL 153
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
1095-1282 9.53e-10

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: 61.36  E-value: 9.53e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1095 HEQVVIHTDQVIGKGHFGVVYHGEYTDEaqNQIhCAIKSlsriteVQEVEAFL-REGLIMRGLHHPNILALIG------- 1166
Cdd:cd14137      1 PVEISYTIEKVIGSGSFGVVYQAKLLET--GEV-VAIKK------VLQDKRYKnRELQIMRRLKHPNIVKLKYffyssge 71
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1167 ---------IMlppEGLPRVLLPYMRHgdllrFIRSPQRVSAQcpgwgvsasthlcrcspvsscpqnpTVKdLISFglQV 1237
Cdd:cd14137     72 kkdevylnlVM---EYMPETLYRVIRH-----YSKNKQTIPII-------------------------YVK-LYSY--QL 115
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 2678964124 1238 ACGMEYLAEQKFVHRDLAARNCMLD-ESFTVKVADFGLARGILDKE 1282
Cdd:cd14137    116 FRGLAYLHSLGICHRDIKPQNLLVDpETGVLKLCDFGSAKRLVPGE 161
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
1104-1275 1.36e-09

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: 60.42  E-value: 1.36e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgEYTDEAQNQiHCAIKSLSRiTEVQEVEAFLR-EGLIMRGLHHPNILALIGIMLPPEGLPRVlLPYM 1182
Cdd:cd14095      6 RVIGDGNFAVVK--ECRDKATDK-EYALKIIDK-AKCKGKEHMIEnEVAILRRVKHPNIVQLIEEYDTDTELYLV-MELV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcSPVSSCpqnpTVKDLISfglqvacGMEYLAEQKFVHRDLAARNCML- 1261
Cdd:cd14095     81 KGGDLFDAITSSTKFT-----------------ERDASR----MVTDLAQ-------ALKYLHSLSIVHRDIKPENLLVv 132
                          170
                   ....*....|....*..
gi 2678964124 1262 ---DESFTVKVADFGLA 1275
Cdd:cd14095    133 eheDGSKSLKLADFGLA 149
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
1106-1315 1.39e-09

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: 60.20  E-value: 1.39e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEaqnqiHCAIKSLSRITEVQeveafLREgliMRGLHHPNILALIGI-MLPPegLPRVLLPYMRH 1184
Cdd:cd14059      1 LGSGAQGAVFLGKFRGE-----EVAVKKVRDEKETD-----IKH---LRKLNHPNIIKFKGVcTQAP--CYCILMEYCPY 65
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnPTVkdLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd14059     66 GQLYEVLRAGREIT--------------------------PSL--LVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYN 117
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1265 FTVKVADFGLARGILDKeyySVRQHRHArlPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14059    118 DVLKISDFGTSKELSEK---STKMSFAG--TVAWMAPEVIRNEPCSEKVDI 163
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
1106-1315 1.39e-09

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: 60.60  E-value: 1.39e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgeytdEAQNQIHCAIKSLSRI---TEVQEVEAF-LREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd07860      8 IGEGTYGVVY------KARNKLTGEVVALKKIrldTETEGVPSTaIREISLLKELNHPNIVKLLDVIHTENKLYLVF-EF 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MrHGDLLRFIRSpqrvsaqCPGWGVSAsthlcrcspvsscpqnPTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd07860     81 L-HQDLKKFMDA-------SALTGIPL----------------PLIK---SYLFQLLQGLAFCHSHRVLHRDLKPQNLLI 133
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1262 DESFTVKVADFGLAR--GIldkeyySVRQHRHARLPVKWMALESLQTYRF-TTKSDV 1315
Cdd:cd07860    134 NTEGAIKLADFGLARafGV------PVRTYTHEVVTLWYRAPEILLGCKYySTAVDI 184
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
1104-1275 1.51e-09

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: 60.41  E-value: 1.51e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgEYTDEAQNQIHCA-IKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYM 1182
Cdd:cd14188      7 KVLGKGGFAKCY--EMTDLTTNKVYAAkIIPHSRVSKPHQREKIDKEIELHRILHHKHVVQFYHYFEDKENI-YILLEYC 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqNPTVKDLISfglQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd14188     84 SRRSMAHILKARKVLT-------------------------EPEVRYYLR---QIVSGLKYLHEQEILHRDLKLGNFFIN 135
                          170
                   ....*....|...
gi 2678964124 1263 ESFTVKVADFGLA 1275
Cdd:cd14188    136 ENMELKVGDFGLA 148
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
1104-1275 1.51e-09

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: 60.09  E-value: 1.51e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGeyTDEAQNQIhCAIKSL--SRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd14073      7 ETLGKGTYGKVKLA--IERATGRE-VAIKSIkkDKIEDEQDMVRIRREIEIMSSLNHPHIIRIYEVFENKDKIVIVM-EY 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd14073     83 ASGGELYDYISERRRL----------------------------PEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILL 134
                          170
                   ....*....|....
gi 2678964124 1262 DESFTVKVADFGLA 1275
Cdd:cd14073    135 DQNGNAKIADFGLS 148
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
1106-1278 2.26e-09

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: 60.50  E-value: 2.26e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTdEAQNQIHCAIKSLSRI-TEVQEVEAFLREGLIMRGLH-HPNILALIGIMLPPEGLPRVLLPYMR 1183
Cdd:cd07857      8 LGQGAYGIVCSARNA-ETSEEETVAIKKITNVfSKKILAKRALRELKLLRHFRgHKNITCLYDMDIVFPGNFNELYLYEE 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 --HGDLLRFIRSPQRVSaqcpgwgvsaSTHLcrcspvsscpqnptvkdlISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd07857     87 lmEADLHQIIRSGQPLT----------DAHF------------------QSFIYQILCGLKYIHSANVLHRDLKPGNLLV 138
                          170
                   ....*....|....*..
gi 2678964124 1262 DESFTVKVADFGLARGI 1278
Cdd:cd07857    139 NADCELKICDFGLARGF 155
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
1106-1276 2.65e-09

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: 59.57  E-value: 2.65e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNqihCAIK-----SLSRITEVQEVEaflREGLIMRGLHHPNILALIGIMLPPEGLpRVLLP 1180
Cdd:cd14081      9 LGKGQTGLVKLAKHCVTGQK---VAIKivnkeKLSKESVLMKVE---REIAIMKLIEHPNVLKLYDVYENKKYL-YLVLE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd14081     82 YVSGGELFDYLVKKGRL----------------------------TEKEARKFFRQIISALDYCHSHSICHRDLKPENLL 133
                          170
                   ....*....|....*.
gi 2678964124 1261 LDESFTVKVADFGLAR 1276
Cdd:cd14081    134 LDEKNNIKIADFGMAS 149
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
1107-1315 3.75e-09

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: 58.82  E-value: 3.75e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1107 GKGHFGVVYHGEYTDEAQnqiHCAIKSLSRITevqeveaflREGLIMRGLHHPNILALIGIMLPPEGLPrVLLPYMRHGD 1186
Cdd:cd14060      2 GGGSFGSVYRAIWVSQDK---EVAVKKLLKIE---------KEAEILSVLSHRNIIQFYGAILEAPNYG-IVTEYASYGS 68
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1187 LLRFIRSPQRvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQ---KFVHRDLAARNCMLDE 1263
Cdd:cd14060     69 LFDYLNSNES--------------------------EEMDMDQIMTWATDIAKGMHYLHMEapvKVIHRDLKSRNVVIAA 122
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1264 SFTVKVADFGLARgildkeYYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd14060    123 DGVLKICDFGASR------FHSHTTHMSLVGTFPWMAPEVIQSLPVSETCDT 168
TIG pfam01833
IPT/TIG domain; This family consists of a domain that has an immunoglobulin like fold. These ...
710-792 4.30e-09

IPT/TIG domain; This family consists of a domain that has an immunoglobulin like fold. These domains are found in cell surface receptors such as Met and Ron as well as in intracellular transcription factors where it is involved in DNA binding. CAUTION: This family does not currently recognize a significant number of members.


Pssm-ID: 460355 [Multi-domain]  Cd Length: 84  Bit Score: 54.76  E-value: 4.30e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  710 PMLTSIKPDFGPRAGGTYLTLEGQSLSVGTSRA-VLVNGTQCRLEQVSEEKILCVTPPGAgTASVPLRLQIGGAEVRGSR 788
Cdd:pfam01833    1 PVITSISPSSGPASGGTTITITGSNFGTDSSDLkVTIGGTPCTVISVSSTTIVCTTPPGT-SGLVNVSVTVGGGGISSSP 79

                   ....*
gi 2678964124  789 -TFHY 792
Cdd:pfam01833   80 lTFTY 84
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
1106-1276 5.93e-09

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: 58.30  E-value: 5.93e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgEYTDEAQNQIHcAIKSL--SRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMR 1183
Cdd:cd05123      1 LGKGSFGKVL--LVRKKDTGKLY-AMKVLrkKEIIKRKEVEHTLNERNILERVNHPFIVKLHYAFQTEEKL-YLVLDYVP 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLrfirspqrvsaqcpgwgvsasTHLCRCSPVSscpqnptvKDLISF-GLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05123     77 GGELF---------------------SHLSKEGRFP--------EERARFyAAEIVLALEYLHSLGIIYRDLKPENILLD 127
                          170
                   ....*....|....
gi 2678964124 1263 ESFTVKVADFGLAR 1276
Cdd:cd05123    128 SDGHIKLTDFGLAK 141
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
1106-1315 5.95e-09

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: 58.91  E-value: 5.95e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeyTDEAQNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd06640     12 IGKGSFGEVFKG--IDNRTQQV-VAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKL-WIIMEYLGGG 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVKDLISfglqvacGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd06640     88 SALDLLRA----------------------GPFDEFQIATMLKEILK-------GLDYLHSEKKIHRDIKAANVLLSEQG 138
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEyysVRQHRHARLPVkWMALESLQTYRFTTKSDV 1315
Cdd:cd06640    139 DVKLADFGVAGQLTDTQ---IKRNTFVGTPF-WMAPEVIQQSAYDSKADI 184
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
1106-1276 7.17e-09

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 59.00  E-value: 7.17e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgEYTDEAQNQIhCAIK-------SLSRITEVQEVE------AFLREGLIMRGLHHPNILALIGIMLPpE 1172
Cdd:PTZ00024    17 LGEGTYGKVE--KAYDTLTGKI-VAIKkvkiieiSNDVTKDRQLVGmcgihfTTLRELKIMNEIKHENIMGLVDVYVE-G 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 GLPRVLLPYMrHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqNPTVKDLIsfgLQVACGMEYLAEQKFVHR 1252
Cdd:PTZ00024    93 DFINLVMDIM-ASDLKKVVDRKIRLT-------------------------ESQVKCIL---LQILNGLNVLHKWYFMHR 143
                          170       180
                   ....*....|....*....|....
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLAR 1276
Cdd:PTZ00024   144 DLSPANIFINSKGICKIADFGLAR 167
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
1106-1276 7.77e-09

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: 58.43  E-value: 7.77e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeyTDEAQNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMrHG 1185
Cdd:cd07870      8 LGEGSYATVYKG--ISRINGQL-VALKVISMKTEEGVPFTAIREASLLKGLKHANIVLLHDIIHTKETLTFVF-EYM-HT 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIrspqrvsAQCPGwgvsaSTHLCrcspvsscpqnptvkDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd07870     83 DLAQYM-------IQHPG-----GLHPY---------------NVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISYLG 135
                          170
                   ....*....|.
gi 2678964124 1266 TVKVADFGLAR 1276
Cdd:cd07870    136 ELKLADFGLAR 146
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
1106-1276 8.04e-09

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: 58.01  E-value: 8.04e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEytdEAQNQIHCAIKSLsRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMRHG 1185
Cdd:cd14103      1 LGRGKFGTVYRCV---EKATGKELAAKFI-KCRKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVM-EYVAGG 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLrfirspQRVsaqcpgwgVSASTHLcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN--CMLDE 1263
Cdd:cd14103     76 ELF------ERV--------VDDDFEL-------------TERDCILFMRQICEGVQYMHKQGILHLDLKPENilCVSRT 128
                          170
                   ....*....|...
gi 2678964124 1264 SFTVKVADFGLAR 1276
Cdd:cd14103    129 GNQIKIIDFGLAR 141
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
1104-1279 9.16e-09

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: 57.80  E-value: 9.16e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQnqiHCAIKSLSRITEVQE----VEAFLREGLIMRGLHHPNILALIGIMLPpEGLPRVLL 1179
Cdd:cd06632      6 QLLGSGSFGSVYEGFNGDTGD---FFAVKEVSLVDDDKKsresVKQLEQEIALLSKLRHPNIVQYYGTERE-EDNLYIFL 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpQNPTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd06632     82 EYVPGGSIHKLLQRYGAF-------------------------EEPVIR---LYTRQILSGLAYLHSRNTVHRDIKGANI 133
                          170       180
                   ....*....|....*....|
gi 2678964124 1260 MLDESFTVKVADFGLARGIL 1279
Cdd:cd06632    134 LVDTNGVVKLADFGMAKHVE 153
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
1104-1276 9.38e-09

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: 57.65  E-value: 9.38e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDeaqNQIHCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd05578      6 RVIGKGSFGKVCIVQKKD---TKKMFAMKYMNKqkCIEKDSVRNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVV-DL 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLlRFirspqrvsaqcpgwgvsastHLCRCSPVSScpqnPTVKDLISfglQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05578     82 LLGGDL-RY--------------------HLQQKVKFSE----ETVKFYIC---EIVLALDYLHSKNIIHRDIKPDNILL 133
                          170
                   ....*....|....*
gi 2678964124 1262 DESFTVKVADFGLAR 1276
Cdd:cd05578    134 DEQGHVHITDFNIAT 148
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
1106-1287 1.10e-08

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: 57.68  E-value: 1.10e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeYTDEAQNQIHcAIK-----SLSRITevqeVEAFLREGLIMRGLHHPNILALIG-------IMLppeg 1173
Cdd:cd14121      3 LGSGTYATVYKA-YRKSGAREVV-AVKcvsksSLNKAS----TENLLTEIELLKKLKHPHIVELKDfqwdeehIYL---- 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1174 lprvLLPYMRHGDLLRFIRSPQRVSAqcpgwgvsastHLCRcspvsscpqnptvkdliSFGLQVACGMEYLAEQKFVHRD 1253
Cdd:cd14121     73 ----IMEYCSGGDLSRFIRSRRTLPE-----------STVR-----------------RFLQQLASALQFLREHNISHMD 120
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 2678964124 1254 LAARNCMLDESFTV--KVADFGLARGI-LDKEYYSVR 1287
Cdd:cd14121    121 LKPQNLLLSSRYNPvlKLADFGFAQHLkPNDEAHSLR 157
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
1103-1273 1.18e-08

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: 57.40  E-value: 1.18e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1103 DQVIGKGHFGVVYHGEYTdEAQNQIHCAIKSLSRITEvQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYM 1182
Cdd:cd14071      5 ERTIGKGNFAVVKLARHR-ITKTEVAIKIIDKSQLDE-ENLKKIYREVQIMKMLNHPHIIKLYQVMETKDMLYLVT-EYA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVS---AQCPGWgvsasthlcrcspvsscpqnptvkdlisfglQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd14071     82 SNGEIFDYLAQHGRMSekeARKKFW-------------------------------QILSAVEYCHKRHIVHRDLKAENL 130
                          170
                   ....*....|....
gi 2678964124 1260 MLDESFTVKVADFG 1273
Cdd:cd14071    131 LLDANMNIKIADFG 144
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
1104-1275 1.20e-08

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: 57.41  E-value: 1.20e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTdeaQNQIHCAIKSL--SRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVlLPY 1181
Cdd:cd14663      6 RTLGEGTFAKVKFARNT---KTGESVAIKIIdkEQVAREGMVEQIKREIAIMKLLRHPNIVELHEVMATKTKIFFV-MEL 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscPQNPTVK---DLISfglqvacGMEYLAEQKFVHRDLAARN 1258
Cdd:cd14663     82 VTGGELFSKIAKNGRL------------------------KEDKARKyfqQLID-------AVDYCHSRGVFHRDLKPEN 130
                          170
                   ....*....|....*..
gi 2678964124 1259 CMLDESFTVKVADFGLA 1275
Cdd:cd14663    131 LLLDEDGNLKISDFGLS 147
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
1104-1276 1.41e-08

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: 57.70  E-value: 1.41e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNqihCAIKSLSRITEvqEVEAFLREGLIMRGL-HHPNILALIGIML--PPEGLPRVL-- 1178
Cdd:cd06608     12 EVIGEGTYGKVYKARHKKTGQL---AAIKIMDIIED--EEEEIKLEINILRKFsNHPNIATFYGAFIkkDPPGGDDQLwl 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 -LPYMRHG---DLLR-FIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptvKDLISFGLQVAC-GMEYLAEQKFVHR 1252
Cdd:cd06608     87 vMEYCGGGsvtDLVKgLRKKGKRLK-----------------------------EEWIAYILRETLrGLAYLHENKVIHR 137
                          170       180
                   ....*....|....*....|....
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd06608    138 DIKGQNILLTEEAEVKLVDFGVSA 161
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
1106-1276 1.44e-08

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: 57.62  E-value: 1.44e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEytDEAQNQIhCAIKslsRITEVQEVEAF----LREGLIMRGLHHPNILALIGIMLPpEGLPRVLL-- 1179
Cdd:cd07843     13 IEEGTYGVVYRAR--DKKTGEI-VALK---KLKMEKEKEGFpitsLREINILLKLQHPNIVTVKEVVVG-SNLDKIYMvm 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHG--DLLRFIRSPQRVSAqcpgwgvsasthlcrcspvsscpqnptVKDLIsfgLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd07843     86 EYVEHDlkSLMETMKQPFLQSE---------------------------VKCLM---LQLLSGVAHLHDNWILHRDLKTS 135
                          170
                   ....*....|....*....
gi 2678964124 1258 NCMLDESFTVKVADFGLAR 1276
Cdd:cd07843    136 NLLLNNRGILKICDFGLAR 154
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
1094-1315 2.35e-08

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: 56.51  E-value: 2.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1094 PHEQVVIhtDQVIGKGHFGVVYHGEYTdeaQNQIHCAIKSLSRITEVQEVEaflREGLIMRGLHHPNILALIGimlppeg 1173
Cdd:cd06612      1 PEEVFDI--LEKLGEGSYGSVYKAIHK---ETGQVVAIKVVPVEEDLQEII---KEISILKQCDSPYIVKYYG------- 65
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1174 lprvllPYMRHGDLLrfIrspqrVSAQCPGWGVSASTHLCrcspvsscpQNPTVKDLISFGL-QVACGMEYLAEQKFVHR 1252
Cdd:cd06612     66 ------SYFKNTDLW--I-----VMEYCGAGSVSDIMKIT---------NKTLTEEEIAAILyQTLKGLEYLHSNKKIHR 123
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLArGILdkeyysvrQHRHARLPVK-----WMALESLQTYRFTTKSDV 1315
Cdd:cd06612    124 DIKAGNILLNEEGQAKLADFGVS-GQL--------TDTMAKRNTVigtpfWMAPEVIQEIGYNNKADI 182
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
1104-1283 3.35e-08

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: 56.43  E-value: 3.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDeaqNQIHCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPY 1181
Cdd:cd05580      7 KTLGTGSFGRVRLVKHKD---SGKYYALKILKKakIIKLKQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNL-YMVMEY 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqNPTVKDLISfglQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05580     83 VPGGELFSLLRRSGRFP-------------------------NDVAKFYAA---EVVLALEYLHSLDIVYRDLKPENLLL 134
                          170       180
                   ....*....|....*....|..
gi 2678964124 1262 DESFTVKVADFGLARGILDKEY 1283
Cdd:cd05580    135 DSDGHIKITDFGFAKRVKDRTY 156
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
1105-1275 3.37e-08

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: 56.20  E-value: 3.37e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEytDEAQNQIHcAIKSLSRITEVQE------VEAFLRE-GLIMRGLHHPNILALIGImLPPEGLPRV 1177
Cdd:cd13993      7 PIGEGAYGVVYLAV--DLRTGRKY-AIKCLYKSGPNSKdgndfqKLPQLREiDLHRRVSRHPNIITLHDV-FETEVAIYI 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRSPQRVsaqcPGwgvsaSTHLCRcspvsscpqnptvkdliSFGLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd13993     83 VLEYCPNGDLFEAITENRIY----VG-----KTELIK-----------------NVFLQLIDAVKHCHSLGIYHRDIKPE 136
                          170
                   ....*....|....*....
gi 2678964124 1258 NCMLDESF-TVKVADFGLA 1275
Cdd:cd13993    137 NILLSQDEgTVKLCDFGLA 155
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
1104-1275 3.51e-08

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: 56.16  E-value: 3.51e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEytDEAQNQIhCAIKSLSrITEVQEVEAFLREGLIMRGLHHPNILALIGimlppeglprvllPYMR 1183
Cdd:cd06613      6 QRIGSGTYGDVYKAR--NIATGEL-AAVKVIK-LEPGDDFEIIQQEISMLKECRHPNIVAYFG-------------SYLR 68
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLlrFIrspqrVSAQCPGWGVSASTHLCRcspvsscpqnPTVKDLISF-GLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd06613     69 RDKL--WI-----VMEYCGGGSLQDIYQVTG----------PLSELQIAYvCRETLKGLAYLHSTGKIHRDIKGANILLT 131
                          170
                   ....*....|...
gi 2678964124 1263 ESFTVKVADFGLA 1275
Cdd:cd06613    132 EDGDVKLADFGVS 144
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
1106-1278 3.63e-08

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: 56.27  E-value: 3.63e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEytDEAQNQIhCAIKSLSRITEVQEVEAF-LREGLIMRGLHHPNILALIGIMLPPeglPRVLLPY--- 1181
Cdd:cd07861      8 IGEGTYGVVYKGR--NKKTGQI-VAMKKIRLESEEEGVPSTaIREISLLKELQHPNIVCLEDVLMQE---NRLYLVFefl 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 -MrhgDLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd07861     82 sM---DLKKYLDS----------------------LPKGKYMDAELVK---SYLYQILQGILFCHSRRVLHRDLKPQNLL 133
                          170
                   ....*....|....*...
gi 2678964124 1261 LDESFTVKVADFGLARGI 1278
Cdd:cd07861    134 IDNKGVIKLADFGLARAF 151
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
1105-1274 3.75e-08

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: 56.93  E-value: 3.75e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEAQNqihCAIKSLSR--ITEVQEVEAFLREGLIMR---GLHHPNILALIGIMLPPEGLPRVLl 1179
Cdd:cd05589      6 VLGRGHFGKVLLAEYKPTGEL---FAIKALKKgdIIARDEVESLMCEKRIFEtvnSARHPFLVNLFACFQTPEHVCFVM- 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIRS-----PQ-RVSAQCpgwgvsasthlcrcspvsscpqnptvkdlisfglqVACGMEYLAEQKFVHRD 1253
Cdd:cd05589     82 EYAAGGDLMMHIHEdvfsePRaVFYAAC-----------------------------------VVLGLQFLHEHKIVYRD 126
                          170       180
                   ....*....|....*....|.
gi 2678964124 1254 LAARNCMLDESFTVKVADFGL 1274
Cdd:cd05589    127 LKLDNLLLDTEGYVKIADFGL 147
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
1106-1315 4.11e-08

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: 56.23  E-value: 4.11e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeytDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd06641     12 IGKGSFGEVFKG---IDNRTQKVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKL-WIIMEYLGGG 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRspqrvsaqcPGwgvsasthlcrcsPVSSCPQNPTVKDLISfglqvacGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd06641     88 SALDLLE---------PG-------------PLDETQIATILREILK-------GLDYLHSEKKIHRDIKAANVLLSEHG 138
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEyysVRQHRHARLPVkWMALESLQTYRFTTKSDV 1315
Cdd:cd06641    139 EVKLADFGVAGQLTDTQ---IKRN*FVGTPF-WMAPEVIKQSAYDSKADI 184
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
1106-1276 4.97e-08

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: 56.22  E-value: 4.97e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQnqihcaIKSLSRITEVQEVEAF----LREGLIMRGLHHPNILALIGIMLPpEGLPRVLL-- 1179
Cdd:cd07845     15 IGEGTYGIVYRARDTTSGE------IVALKKVRMDNERDGIpissLREITLLLNLRHPNIVELKEVVVG-KHLDSIFLvm 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHgDLLRFIRSPQRvsaqcpgwgvsasthlcrcsPVSScpqnPTVKDLIsfgLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd07845     88 EYCEQ-DLASLLDNMPT--------------------PFSE----SQVKCLM---LQLLRGLQYLHENFIIHRDLKVSNL 139
                          170
                   ....*....|....*..
gi 2678964124 1260 MLDESFTVKVADFGLAR 1276
Cdd:cd07845    140 LLTDKGCLKIADFGLAR 156
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
1106-1276 6.06e-08

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: 55.45  E-value: 6.06e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIhcAIKSLSRiTEVQEVEAFL-REGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMRH 1184
Cdd:cd14120      1 IGHGAFAVVFKGRHRKKPDLPV--AIKCITK-KNLSKSQNLLgKEIKILKELSHENVVALLDCQETSSSVYLVM-EYCNG 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 GDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptvKDLI-SFGLQVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd14120     77 GDLADYLQAKGTLS-----------------------------EDTIrVFLQQIAAAMKALHSKGIVHRDLKPQNILLSH 127
                          170       180
                   ....*....|....*....|..
gi 2678964124 1264 S---------FTVKVADFGLAR 1276
Cdd:cd14120    128 NsgrkpspndIRLKIADFGFAR 149
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
1105-1276 6.47e-08

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: 55.96  E-value: 6.47e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYhgeytdEAQNQIHCAIKSLSRITEVQEVEAF----LREGLIMRGLHHPNILALIGIM---------LPP 1171
Cdd:cd07864     14 IIGEGTYGQVY------KAKDKDTGELVALKKVRLDNEKEGFpitaIREIKILRQLNHRSVVNLKEIVtdkqdaldfKKD 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1172 EGLPRVLLPYMRHgDLLRFIRSpqrvsaqcpGWGVSASTHLCrcspvsscpqnptvkdliSFGLQVACGMEYLAEQKFVH 1251
Cdd:cd07864     88 KGAFYLVFEYMDH-DLMGLLES---------GLVHFSEDHIK------------------SFMKQLLEGLNYCHKKNFLH 139
                          170       180
                   ....*....|....*....|....*
gi 2678964124 1252 RDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd07864    140 RDIKCSNILLNNKGQIKLADFGLAR 164
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
1106-1276 9.31e-08

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: 55.13  E-value: 9.31e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgeytdEAQNQIHCAIKSLSRITEVQEVEAF----LREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd07839      8 IGEGTYGTVF------KAKNRETHEIVALKRVRLDDDDEGVpssaLREICLLKELKHKNIVRLYDVLHSDKKLTLVF-EY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHgDLLRFIRSpqrvsaqCPGWgvsasthlcrcspvsscPQNPTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd07839     81 CDQ-DLKKYFDS-------CNGD-----------------IDPEIVK---SFMFQLLKGLAFCHSHNVLHRDLKPQNLLI 132
                          170
                   ....*....|....*
gi 2678964124 1262 DESFTVKVADFGLAR 1276
Cdd:cd07839    133 NKNGELKLADFGLAR 147
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
1106-1315 1.07e-07

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: 55.06  E-value: 1.07e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeyTDEAQNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd06642     12 IGKGSFGEVYKG--IDNRTKEV-VAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKL-WIIMEYLGGG 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRspqrvsaqcPGwgvsasthlcrcsPVSSCPQNPTVKDLISfglqvacGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd06642     88 SALDLLK---------PG-------------PLEETYIATILREILK-------GLDYLHSERKIHRDIKAANVLLSEQG 138
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEyysVRQHRHARLPVkWMALESLQTYRFTTKSDV 1315
Cdd:cd06642    139 DVKLADFGVAGQLTDTQ---IKRNTFVGTPF-WMAPEVIKQSAYDFKADI 184
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
1106-1314 1.15e-07

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: 54.61  E-value: 1.15e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEY--TDEaqnqiHCAIKSL--SRITEVqeveafLREGLIMRGLHHPNILA------------LIgiml 1169
Cdd:cd14010      8 IGRGKHSVVYKGRRkgTIE-----FVAIKCVdkSKRPEV------LNEVRLTHELKHPNVLKfyewyetsnhlwLV---- 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1170 ppeglprvlLPYMRHGDLLRFIRSpqrvsaqcpgwgvsaSTHLcrcspvsscpQNPTVKDlisFGLQVACGMEYLAEQKF 1249
Cdd:cd14010     73 ---------VEYCTGGDLETLLRQ---------------DGNL----------PESSVRK---FGRDLVRGLHYIHSKGI 115
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1250 VHRDLAARNCMLDESFTVKVADFGLAR---GILDKEYYSVRQHRHARLPVK---------WMALESLQTYRFTTKSD 1314
Cdd:cd14010    116 IYCDLKPSNILLDGNGTLKLSDFGLARregEILKELFGQFSDEGNVNKVSKkqakrgtpyYMAPELFQGGVHSFASD 192
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
1104-1315 1.27e-07

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: 54.88  E-value: 1.27e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgeytdEAQNQIH-C--AIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIML--PPEGLPRvl 1178
Cdd:cd14048     12 QCLGRGGFGVVF------EAKNKVDdCnyAVKRIRLPNNELAREKVLREVRALAKLDHPGIVRYFNAWLerPPEGWQE-- 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 lpymRHGDLLRFIRSPQRVSAQCPGWGVSASTHLCRcsPVSSCpqnptvkdlISFGLQVACGMEYLAEQKFVHRDLAARN 1258
Cdd:cd14048     84 ----KMDEVYLYIQMQLCRKENLKDWMNRRCTMESR--ELFVC---------LNIFKQIASAVEYLHSKGLIHRDLKPSN 148
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1259 CMLDESFTVKVADFGLARGI-LDKEYYSVRQ-----HRHA-RLPVK-WMALESLQTYRFTTKSDV 1315
Cdd:cd14048    149 VFFSLDDVVKVGDFGLVTAMdQGEPEQTVLTpmpayAKHTgQVGTRlYMSPEQIHGNQYSEKVDI 213
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
1104-1275 1.28e-07

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: 54.64  E-value: 1.28e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVY--HGEYTDEAqnqihCAIKSLSRITEVQE-VEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLP 1180
Cdd:cd14069      7 QTLGEGAFGEVFlaVNRNTEEA-----VAVKFVDMKRAPGDcPENIKKEVCIQKMLSHKNVVRFYGHRREGEFQ-YLFLE 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRspqrvsaqcPGWGVSasthlcrcspvsscpqnptvKDLISFGL-QVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd14069     81 YASGGELFDKIE---------PDVGMP--------------------EDVAQFYFqQLMAGLKYLHSCGITHRDIKPENL 131
                          170
                   ....*....|....*.
gi 2678964124 1260 MLDESFTVKVADFGLA 1275
Cdd:cd14069    132 LLDENDNLKISDFGLA 147
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
1101-1278 1.93e-07

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: 53.79  E-value: 1.93e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1101 HTDQVIGKGHFGVVYHG--EYTDEAqnqihCAIKSLSRI--TEvQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpr 1176
Cdd:cd14002      4 HVLELIGEGSFGKVYKGrrKYTGQV-----VALKFIPKRgkSE-KELRNLRQEIEILRKLNHPNIIEMLDSFETKKEF-- 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 VLLPYMRHGDLLRFIRS----P----QRVSAQCpgwgVSAsthlcrcspvsscpqnptvkdlisfglqvacgMEYLAEQK 1248
Cdd:cd14002     76 VVVTEYAQGELFQILEDdgtlPeeevRSIAKQL----VSA--------------------------------LHYLHSNR 119
                          170       180       190
                   ....*....|....*....|....*....|
gi 2678964124 1249 FVHRDLAARNCMLDESFTVKVADFGLARGI 1278
Cdd:cd14002    120 IIHRDMKPQNILIGKGGVVKLCDFGFARAM 149
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
1106-1299 2.23e-07

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: 54.66  E-value: 2.23e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHgeyTDEAQNQIHCAIKSLSR-ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRV----LLP 1180
Cdd:cd07877     25 VGSGAYGSVCA---AFDTKTGLRVAVKKLSRpFQSIIHAKRTYRELRLLKHMKHENVIGLLDVFTPARSLEEFndvyLVT 101
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLlrfirspqrvsaqcpgwgvsasTHLCRCSPVSScpqnptvkDLISFGL-QVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd07877    102 HLMGADL----------------------NNIVKCQKLTD--------DHVQFLIyQILRGLKYIHSADIIHRDLKPSNL 151
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 2678964124 1260 MLDESFTVKVADFGLARGILDKE--YYSVRQHRHARLPVKWM 1299
Cdd:cd07877    152 AVNEDCELKILDFGLARHTDDEMtgYVATRWYRAPEIMLNWM 193
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
1106-1283 2.39e-07

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: 53.98  E-value: 2.39e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgeYTDEAQNQIHCAIKSLSrITEV---QEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYM 1182
Cdd:cd05612      9 IGTGTFGRVH---LVRDRISEHYYALKVMA-IPEVirlKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFL-YMLMEYV 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVSAqcpgwgvsaSTHLCrcspvsscpqnptvkdlisFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd05612     84 PGGELFSYLRNSGRFSN---------STGLF-------------------YASEIVCALEYLHSKEIVYRDLKPENILLD 135
                          170       180
                   ....*....|....*....|.
gi 2678964124 1263 ESFTVKVADFGLARGILDKEY 1283
Cdd:cd05612    136 KEGHIKLTDFGFAKKLRDRTW 156
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
1104-1275 2.42e-07

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: 53.68  E-value: 2.42e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVyhgEYTDEAQNQIHCAIKSLSRiTEVQ--EVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPY 1181
Cdd:cd14072      6 KTIGKGNFAKV---KLARHVLTGREVAIKIIDK-TQLNpsSLQKLFREVRIMKILNHPNIVKLFEVIETEKTL-YLVMEY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSAqcpgwgvsasthlcrcspvsscpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd14072     81 ASGGEVFDYLVAHGRMKE----------------------------KEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLL 132
                          170
                   ....*....|....
gi 2678964124 1262 DESFTVKVADFGLA 1275
Cdd:cd14072    133 DADMNIKIADFGFS 146
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
1104-1276 2.49e-07

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 54.40  E-value: 2.49e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNqihCAIKSLSRITE-VQEVEAFLREGLIMRGLHHPNILALIGIMLPPEglPR------ 1176
Cdd:cd07859      6 EVIGKGSYGVVCSAIDTHTGEK---VAIKKINDVFEhVSDATRILREIKLLRLLRHPDIVEIKHIMLPPS--RRefkdiy 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 VLLPYMrHGDLLRFIRspqrvsaqcpgwgvsASTHLcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd07859     81 VVFELM-ESDLHQVIK---------------ANDDL-------------TPEHHQFFLYQLLRALKYIHTANVFHRDLKP 131
                          170       180
                   ....*....|....*....|
gi 2678964124 1257 RNCMLDESFTVKVADFGLAR 1276
Cdd:cd07859    132 KNILANADCKLKICDFGLAR 151
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
1106-1276 2.50e-07

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: 53.81  E-value: 2.50e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQnqiHCAIKSLS--------RITEVQEVeAFLREgliMRGLHHPNILALIGI--MLPPEGLP 1175
Cdd:cd07863      8 IGVGAYGTVYKARDPHSGH---FVALKSVRvqtnedglPLSTVREV-ALLKR---LEAFDHPNIVRLMDVcaTSRTDRET 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1176 RVLLPYMRHGDLLRfirspqrvsaqcpgwgvsasTHLCRCSPvsscPQNP--TVKDLISfglQVACGMEYLAEQKFVHRD 1253
Cdd:cd07863     81 KVTLVFEHVDQDLR--------------------TYLDKVPP----PGLPaeTIKDLMR---QFLRGLDFLHANCIVHRD 133
                          170       180
                   ....*....|....*....|...
gi 2678964124 1254 LAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd07863    134 LKPENILVTSGGQVKLADFGLAR 156
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1104-1315 2.92e-07

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: 53.31  E-value: 2.92e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgEYTDEAQNQIHCaIKSLS--RITEvQEVEAFLREGLIMRGLHHPNILALIG-IMLPPEGLPRVLLP 1180
Cdd:cd08217      6 ETIGKGSFGTVR--KVRRKSDGKILV-WKEIDygKMSE-KEKQQLVSEVNILRELKHPNIVRYYDrIVDRANTTLYIVME 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVSAQCPG---WGVSA--STHLCRCspvsscpQNPTVKDlisfglqvacgmeylaeQKFVHRDLA 1255
Cdd:cd08217     82 YCEGGDLAQLIKKCKKENQYIPEefiWKIFTqlLLALYEC-------HNRSVGG-----------------GKILHRDLK 137
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1256 ARNCMLDESFTVKVADFGLARgILDKEyySVRQHRHARLPVkWMALESLQTYRFTTKSDV 1315
Cdd:cd08217    138 PANIFLDSDNNVKLGDFGLAR-VLSHD--SSFAKTYVGTPY-YMSPELLNEQSYDEKSDI 193
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
1106-1276 3.51e-07

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: 53.53  E-value: 3.51e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgeytdEAQNQIHCAIKSLSRITEVQEVEAF----LREGLIMRGLHHPNILALIGIM-LPPEGLPR---- 1176
Cdd:cd07865     20 IGQGTFGEVF------KARHRKTGQIVALKKVLMENEKEGFpitaLREIKILQLLKHENVVNLIEICrTKATPYNRykgs 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 --VLLPYMRHgDLLRFIrspqrvsaqcpgwgvsasthlcrcspvsscpQNPTVKdlisFGL--------QVACGMEYLAE 1246
Cdd:cd07865     94 iyLVFEFCEH-DLAGLL-------------------------------SNKNVK----FTLseikkvmkMLLNGLYYIHR 137
                          170       180       190
                   ....*....|....*....|....*....|
gi 2678964124 1247 QKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd07865    138 NKILHRDMKAANILITKDGVLKLADFGLAR 167
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
1105-1276 6.39e-07

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: 52.62  E-value: 6.39e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDE---------------AQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIML 1169
Cdd:cd14000      1 LLGDGGFGSVYRASYKGEpvavkifnkhtssnfANVPADTMLRHLRATDAMKNFRLLRQELTVLSHLHHPSIVYLLGIGI 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1170 PPEGLPRVLLPymrhgdllrfirspqrvsaqcpgwgVSASTHLCRCSPVSSCPQNPTVKDLISfgLQVACGMEYLAEQKF 1249
Cdd:cd14000     81 HPLMLVLELAP-------------------------LGSLDHLLQQDSRSFASLGRTLQQRIA--LQVADGLRYLHSAMI 133
                          170       180       190
                   ....*....|....*....|....*....|..
gi 2678964124 1250 VHRDLAARNCML-----DESFTVKVADFGLAR 1276
Cdd:cd14000    134 IYRDLKSHNVLVwtlypNSAIIIKIADYGISR 165
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
1106-1276 6.99e-07

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: 52.61  E-value: 6.99e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVV--YHGEYTDEAQnqihcAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGImlPPE------GLPRV 1177
Cdd:cd14039      1 LGTGGFGNVclYQNQETGEKI-----AIKSCRLELSVKNKDRWCHEIQIMKKLNHPNVVKACDV--PEEmnflvnDVPLL 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRSPQrvsaQCPGWGVSasthlcrcspvsscpqnpTVKDLISfglQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd14039     74 AMEYCSGGDLRKLLNKPE----NCCGLKES------------------QVLSLLS---DIGSGIQYLHENKIIHRDLKPE 128
                          170       180
                   ....*....|....*....|..
gi 2678964124 1258 NCMLDE---SFTVKVADFGLAR 1276
Cdd:cd14039    129 NIVLQEingKIVHKIIDLGYAK 150
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
1104-1276 8.45e-07

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: 52.69  E-value: 8.45e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVV---YHGeytdeaQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPP--EGLPRVL 1178
Cdd:cd07849     11 SYIGEGAYGMVcsaVHK------PTGQKVAIKKISPFEHQTYCLRTLREIKILLRFKHENIIGILDIQRPPtfESFKDVY 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 L--PYMRhGDLLRFIRSpQRVSAQcpgwgvsastHLCrcspvsscpqnptvkdliSFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd07849     85 IvqELME-TDLYKLIKT-QHLSND----------HIQ------------------YFLYQILRGLKYIHSANVLHRDLKP 134
                          170       180
                   ....*....|....*....|
gi 2678964124 1257 RNCMLDESFTVKVADFGLAR 1276
Cdd:cd07849    135 SNLLLNTNCDLKICDFGLAR 154
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
1096-1276 9.62e-07

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: 51.84  E-value: 9.62e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1096 EQVVIHTDQVIGKGHFGVVYHgeyTDEAQNQIHCAIKSLSRITEvQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLP 1175
Cdd:cd14190      2 STFSIHSKEVLGGGKFGKVHT---CTEKRTGLKLAAKVINKQNS-KDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIV 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1176 rVLLPYMRHGDLLRFIrspqrvsaqcpgwgVSASTHLcrcspvsscpqnpTVKDLISFGLQVACGMEYLAEQKFVHRDLA 1255
Cdd:cd14190     78 -LFMEYVEGGELFERI--------------VDEDYHL-------------TEVDAMVFVRQICEGIQFMHQMRVLHLDLK 129
                          170       180
                   ....*....|....*....|...
gi 2678964124 1256 ARN--CMLDESFTVKVADFGLAR 1276
Cdd:cd14190    130 PENilCVNRTGHQVKIIDFGLAR 152
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
1106-1276 1.04e-06

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: 51.91  E-value: 1.04e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgeytdEAQNQIHCAIKSLSRITEVQEVEAF----LREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd07835      7 IGEGTYGVVY------KARDKLTGEIVALKKIRLETEDEGVpstaIREISLLKELNHPNIVRLLDVVHSENKLYLVF-EF 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHgDLLRFIrspqrvsaqcpgwgvsasthlcrcspvSSCPQNPTVKDLI-SFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd07835     80 LDL-DLKKYM---------------------------DSSPLTGLDPPLIkSYLYQLLQGIAFCHSHRVLHRDLKPQNLL 131
                          170
                   ....*....|....*.
gi 2678964124 1261 LDESFTVKVADFGLAR 1276
Cdd:cd07835    132 IDTEGALKLADFGLAR 147
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
1105-1276 1.04e-06

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: 52.22  E-value: 1.04e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEY--TDEAqnqihCAIKSLS--RITEVQEVEAFLREGLIMR-GLHHPNILALIGIMLPPEGLPRVLl 1179
Cdd:cd05570      2 VLGKGSFGKVMLAERkkTDEL-----YAIKVLKkeVIIEDDDVECTMTEKRVLAlANRHPFLTGLHACFQTEDRLYFVM- 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLL-------RFIRSPQRVSAQCpgwgvsasthlcrcspvsscpqnptvkdlisfglqVACGMEYLAEQKFVHR 1252
Cdd:cd05570     76 EYVNGGDLMfhiqrarRFTEERARFYAAE-----------------------------------ICLALQFLHERGIIYR 120
                          170       180
                   ....*....|....*....|....
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd05570    121 DLKLDNVLLDAEGHIKIADFGMCK 144
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
1106-1276 1.07e-06

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: 51.56  E-value: 1.07e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFG----VVYHGEYTDEAQNQIHcaiKSLSRITEvqeveaFLREGLIMRGL-HHPNILALIGIMLPPEGLPRVLLP 1180
Cdd:cd13987      1 LGEGTYGkvllAVHKGSGTKMALKFVP---KPSTKLKD------FLREYNISLELsVHPHIIKTYDVAFETEDYYVFAQE 71
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIrSPQRvsaqcpgwGVSASThlcrcspVSSCPQnptvkdlisfglQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd13987     72 YAPYGDLFSII-PPQV--------GLPEER-------VKRCAA------------QLASALDFMHSKNLVHRDIKPENVL 123
                          170
                   ....*....|....*...
gi 2678964124 1261 L-DESFT-VKVADFGLAR 1276
Cdd:cd13987    124 LfDKDCRrVKLCDFGLTR 141
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
1104-1275 1.34e-06

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: 51.59  E-value: 1.34e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAqnqihCAIKSLSRitevQEVEAFLREGLIMR--GLHHPNILALIGI--MLPPEGL--PRV 1177
Cdd:cd14054      1 QLIGQGRYGTVWKGSLDERP-----VAVKVFPA----RHRQNFQNEKDIYElpLMEHSNILRFIGAdeRPTADGRmeYLL 71
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRspqrvsAQCPGWGVSasthlCRcspvsscpqnptvkdlisFGLQVACGMEYLAEQK--------- 1248
Cdd:cd14054     72 VLEYAPKGSLCSYLR------ENTLDWMSS-----CR------------------MALSLTRGLAYLHTDLrrgdqykpa 122
                          170       180
                   ....*....|....*....|....*..
gi 2678964124 1249 FVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14054    123 IAHRDLNSRNVLVKADGSCVICDFGLA 149
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
1106-1277 1.45e-06

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: 51.62  E-value: 1.45e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeytdeaQNQIHCAIKSLsRITEVQEVEAF----LREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd07869     13 LGEGSYATVYKG------KSKVNGKLVAL-KVIRLQEEEGTpftaIREASLLKGLKHANIVLLHDIIHTKETLTLVF-EY 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MrHGDLLRFIRSpqrvsaqcpgwgvsasthlcrcSPVSSCPQNPTVkdlisFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd07869     85 V-HTDLCQYMDK----------------------HPGGLHPENVKL-----FLFQLLRGLSYIHQRYILHRDLKPQNLLI 136
                          170
                   ....*....|....*.
gi 2678964124 1262 DESFTVKVADFGLARG 1277
Cdd:cd07869    137 SDTGELKLADFGLARA 152
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
1104-1317 1.66e-06

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: 51.16  E-value: 1.66e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAqnqihcAIK--SLSRITEVQeVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVllpy 1181
Cdd:cd14153      6 ELIGKGRFGQVYHGRWHGEV------AIRliDIERDNEEQ-LKAFKREVMAYRQTRHENVVLFMGACMSPPHLAII---- 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 mrhgdllrfirspqrvsaqcpgwgvsasTHLCRCSPVSSCPQNPTVKDLISFGLQVAC----GMEYLAEQKFVHRDLAAR 1257
Cdd:cd14153     75 ----------------------------TSLCKGRTLYSVVRDAKVVLDVNKTRQIAQeivkGMGYLHAKGILHKDLKSK 126
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1258 NCMLDESfTVKVADFGL--ARGILDkeyySVRQHRHARLPVKW---MALESLQTYRFTTKSDVVP 1317
Cdd:cd14153    127 NVFYDNG-KVVITDFGLftISGVLQ----AGRREDKLRIQSGWlchLAPEIIRQLSPETEEDKLP 186
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
1130-1298 1.68e-06

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: 51.70  E-value: 1.68e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1130 AIKSLSrITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPpeglprvllpymRHGDLLRFIRSPQRVSAQCPGWGVsAS 1209
Cdd:cd07854     34 AVKKIV-LTDPQSVKHALREIKIIRRLDHDNIVKVYEVLGP------------SGSDLTEDVGSLTELNSVYIVQEY-ME 99
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1210 THLCRCspvssCPQNPTVKDLIS-FGLQVACGMEYLAEQKFVHRDLAARNCMLD-ESFTVKVADFGLARgILDKEyYSVR 1287
Cdd:cd07854    100 TDLANV-----LEQGPLSEEHARlFMYQLLRGLKYIHSANVLHRDLKPANVFINtEDLVLKIGDFGLAR-IVDPH-YSHK 172
                          170
                   ....*....|.
gi 2678964124 1288 QHRHARLPVKW 1298
Cdd:cd07854    173 GYLSEGLVTKW 183
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
1106-1276 1.73e-06

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: 51.18  E-value: 1.73e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgEYTDEAQNQIhCAIK--SLSRITEVQEVEAfLREGLIMRGL-HHPNILALIGIMLPPEGLPRVLlPYM 1182
Cdd:cd07832      8 IGEGAHGIVF--KAKDRETGET-VALKkvALRKLEGGIPNQA-LREIKALQACqGHPYVVKLRDVFPHGTGFVLVF-EYM 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHgDLLRFIRSPQRvsaqcpgwgvsasthlcrcsPVSScpqnPTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd07832     83 LS-SLSEVLRDEER--------------------PLTE----AQVK---RYMRMLLKGVAYMHANRIMHRDLKPANLLIS 134
                          170
                   ....*....|....
gi 2678964124 1263 ESFTVKVADFGLAR 1276
Cdd:cd07832    135 STGVLKIADFGLAR 148
IPT_plexin_repeat1 cd01180
First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are ...
710-794 1.92e-06

First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present preceeded by SEMA (semaphorin) and PSI (plexin, semaphorin, integrin) domains.


Pssm-ID: 238585  Cd Length: 94  Bit Score: 47.31  E-value: 1.92e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  710 PMLTSIKPDFGPRAGGTYLTLEGQSL--SVGTSR-AVLVNGTQCRLEQ---VSEEKILCVTPPG---AGTASVplRLQIG 780
Cdd:cd01180      1 PVITEFFPLSGPLEGGTRLTICGSNLglRKNDVRhGVRVGGVPCNPEPpeySSSEKIVCTTGPAgnpVFNGPV--EVTVG 78
                           90
                   ....*....|....*.
gi 2678964124  781 GAEVRG--SRTFHYKE 794
Cdd:cd01180     79 HGSFRTesSEGFSFVD 94
IPT cd00102
Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as ...
595-651 2.07e-06

Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor receptors), as well as, cyclodextrin glycosyltransferase and similar enzymes. Although they are involved in DNA binding in transcription factors, their function in other proteins is unknown. In these transcription factors, IPTs form homo- or heterodimers with the exception of the nuclear factor of activated Tcells (NFAT) transcription factors which are mainly monomers.


Pssm-ID: 238050 [Multi-domain]  Cd Length: 89  Bit Score: 47.07  E-value: 2.07e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124  595 PEITEFHPHSGPLRGTTRLTLCGSNFYLRPDGVVpegthqiTV-GQSPCRLLPKDSST 651
Cdd:cd00102      1 PVITSISPSSGPVSGGTEVTITGSNFGSGSNLRV-------TFgGGVPCSVLSVSSTA 51
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
1106-1278 2.33e-06

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: 50.94  E-value: 2.33e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEytDEAQNQIhCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMrHG 1185
Cdd:cd07836      8 LGEGTYATVYKGR--NRTTGEI-VALKEIHLDAEEGTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVF-EYM-DK 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSpqrvsaqcpgwgvsaSTHLCRCSPVsscpqnpTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd07836     83 DLKKYMDT---------------HGVRGALDPN-------TVK---SFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRG 137
                          170
                   ....*....|...
gi 2678964124 1266 TVKVADFGLARGI 1278
Cdd:cd07836    138 ELKLADFGLARAF 150
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
1104-1315 2.36e-06

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: 50.85  E-value: 2.36e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEaqnqiHCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIM--LPPEGLPRVLLPY 1181
Cdd:cd13979      9 EPLGSGGFGSVYKATYKGE-----TVAVKIVRRRRKNRASRQSFWAELNAARLRHENIVRVLAAEtgTDFASLGLIIMEY 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQrvsaqcpgwgvsasthlcrcSPVSscpqnptVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd13979     84 CGNGTLQQLIYEGS--------------------EPLP-------LAHRILISLDIARALRFCHSHGIVHLDVKPANILI 136
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1262 DESFTVKVADFG---LARGILDKEYYSvrqhRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd13979    137 SEQGVCKLCDFGcsvKLGEGNEVGTPR----SHIGGTYTYRAPELLKGERVTPKADI 189
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
1106-1276 2.44e-06

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: 50.49  E-value: 2.44e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNQIHCAIkSLSRITEVQEVEAfLREGLIMRGLHHPNILALIGIMLPpEGLPRVLLPYMRHG 1185
Cdd:cd08529      8 LGKGSFGVVYKVVRKVDGRVYALKQI-DISRMSRKMREEA-IDEARVLSKLNSPYVIKYYDSFVD-KGKLNIVMEYAENG 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFIRSpQRVSaqcpgwgvsasthlcrcspvsscpqnPTVKDLI-SFGLQVACGMEYLAEQKFVHRDLAARNCMLDES 1264
Cdd:cd08529     85 DLHSLIKS-QRGR--------------------------PLPEDQIwKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKG 137
                          170
                   ....*....|..
gi 2678964124 1265 FTVKVADFGLAR 1276
Cdd:cd08529    138 DNVKIGDLGVAK 149
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
1106-1315 2.54e-06

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: 50.90  E-value: 2.54e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQnqihcaiKSLSRITEVQ---EVEAFLREGLIMRGLHHPNILALIGImlppeglprvllpYM 1182
Cdd:cd06611     13 LGDGAFGKVYKAQHKETGL-------FAAAKIIQIEseeELEDFMVEIDILSECKHPNIVGLYEA-------------YF 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSpqrvsaqCPGWGVSAsthlcrcspVSSCPQNPTVKDLISF-GLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd06611     73 YENKLWILIEF-------CDGGALDS---------IMLELERGLTEPQIRYvCRQMLEALNFLHSHKVIHRDLKAGNILL 136
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1262 DESFTVKVADFGL-ARGIldkeyySVRQHRHARLPVK-WMALESL--QTYR---FTTKSDV 1315
Cdd:cd06611    137 TLDGDVKLADFGVsAKNK------STLQKRDTFIGTPyWMAPEVVacETFKdnpYDYKADI 191
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
1106-1290 2.66e-06

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: 50.73  E-value: 2.66e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEytdEAQNQIHCAIKSL-SRITEVQEVEAfLREGLIMRGL-HHPNILALIGIML-PPEGLPRVLLPYM 1182
Cdd:cd07831      7 IGEGTFSEVLKAQ---SRKTGKYYAIKCMkKHFKSLEQVNN-LREIQALRRLsPHPNILRLIEVLFdRKTGRLALVFELM 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 rHGDLLRFIRSPQRvsaqcpgwgvsastHLcrcspvsscPQNpTVKdliSFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd07831     83 -DMNLYELIKGRKR--------------PL---------PEK-RVK---NYMYQLLKSLDHMHRNGIFHRDIKPENILIK 134
                          170       180       190
                   ....*....|....*....|....*....|..
gi 2678964124 1263 ESfTVKVADFGLARGILDK----EYYSVRQHR 1290
Cdd:cd07831    135 DD-ILKLADFGSCRGIYSKppytEYISTRWYR 165
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
1106-1275 3.23e-06

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: 50.44  E-value: 3.23e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeYTDEAQNqiHCAIKSLSRITEVQEV----------------------EAFLREGLIMRGLHHPNILA 1163
Cdd:cd14118      2 IGKGSYGIVKLA-YNEEDNT--LYAMKILSKKKLLKQAgffrrppprrkpgalgkpldplDRVYREIAILKKLDHPNVVK 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1164 LIGIMLPP-EGLPRVLLPYMRHGDLLRfIRSPQRVSAQcpgwgvSASTHLcrcspvsscpqnptvKDLIsfglqvaCGME 1242
Cdd:cd14118     79 LVEVLDDPnEDNLYMVFELVDKGAVME-VPTDNPLSEE------TARSYF---------------RDIV-------LGIE 129
                          170       180       190
                   ....*....|....*....|....*....|...
gi 2678964124 1243 YLAEQKFVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14118    130 YLHYQKIIHRDIKPSNLLLGDDGHVKIADFGVS 162
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
1101-1281 3.30e-06

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: 50.47  E-value: 3.30e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1101 HTDQVIGKGHFGVVYHGeYTDEAQNQIhcAIK-------SLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEG 1173
Cdd:cd14084      9 IMSRTLGSGACGEVKLA-YDKSTCKKV--AIKiinkrkfTIGSRREINKPRNIETEIEILKKLSHPCIIKIEDFFDAEDD 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1174 LPRVLlPYMRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqNPTVKdLISFglQVACGMEYLAEQKFVHRD 1253
Cdd:cd14084     86 YYIVL-ELMEGGELFDRVVSNKRLK-------------------------EAICK-LYFY--QMLLAVKYLHSNGIIHRD 136
                          170       180       190
                   ....*....|....*....|....*....|.
gi 2678964124 1254 LAARNCML---DESFTVKVADFGLARgILDK 1281
Cdd:cd14084    137 LKPENVLLssqEEECLIKITDFGLSK-ILGE 166
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
1228-1273 3.41e-06

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 47.82  E-value: 3.41e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2678964124 1228 KDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFG 1273
Cdd:cd13968     91 KDVESIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
1106-1273 5.92e-06

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: 49.26  E-value: 5.92e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeytdeaqnqIHC------AIKSLSRITEVQEVEAFL-REGLIMRGLHHPNILALIGIMlppEGLPRVL 1178
Cdd:cd14075     10 LGSGNFSQVKLG---------IHQltkekvAIKILDKTKLDQKTQRLLsREISSMEKLHHPNIIRLYEVV---ETLSKLH 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 L--PYMRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqNPTVKDLISfglQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd14075     78 LvmEYASGGELYTKISTEGKLS-------------------------ESEAKPLFA---QIVSAVKHMHENNIIHRDLKA 129
                          170
                   ....*....|....*..
gi 2678964124 1257 RNCMLDESFTVKVADFG 1273
Cdd:cd14075    130 ENVFYASNNCVKVGDFG 146
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
1096-1276 6.84e-06

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: 49.92  E-value: 6.84e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1096 EQVVIHtdQVIGKGHFGVVYHGEYTDEAQnqiHCAIKSLSR--ITEVQEVEAFLREGLIMR-GLHHPNILALIGIMLPPE 1172
Cdd:cd05619      5 EDFVLH--KMLGKGSFGKVFLAELKGTNQ---FFAIKALKKdvVLMDDDVECTMVEKRVLSlAWEHPFLTHLFCTFQTKE 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1173 GLPRVLlPYMRHGDLLRFIRSpqrvsaqCPGWGVSASTHlcrcspvsscpqnptvkdlisFGLQVACGMEYLAEQKFVHR 1252
Cdd:cd05619     80 NLFFVM-EYLNGGDLMFHIQS-------CHKFDLPRATF---------------------YAAEIICGLQFLHSKGIVYR 130
                          170       180
                   ....*....|....*....|....
gi 2678964124 1253 DLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd05619    131 DLKLDNILLDKDGHIKIADFGMCK 154
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
1225-1276 7.75e-06

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 50.18  E-value: 7.75e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2678964124 1225 PTVKDLI------------SFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:NF033483    92 RTLKDYIrehgplspeeavEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIAR 155
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
1104-1275 8.27e-06

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: 49.29  E-value: 8.27e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgeytdEAQNQI---HCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILaligimlppeglpRVLLP 1180
Cdd:cd14046     12 QVLGKGAFGQVV------KVRNKLdgrYYAIKKIKLRSESKNNSRILREVMLLSRLNHQHVV-------------RYYQA 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLlrFIRspqrvsaqcpgwgvsasthlcrcspVSSCPqNPTVKDLISFGL------------QVACGMEYLAEQK 1248
Cdd:cd14046     73 WIERANL--YIQ-------------------------MEYCE-KSTLRDLIDSGLfqdtdrlwrlfrQILEGLAYIHSQG 124
                          170       180
                   ....*....|....*....|....*..
gi 2678964124 1249 FVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14046    125 IIHRDLKPVNIFLDSNGNVKIGDFGLA 151
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
1232-1274 8.81e-06

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: 49.09  E-value: 8.81e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2678964124 1232 SFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGL 1274
Cdd:cd14045    107 SFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGL 149
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
1106-1284 8.94e-06

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: 49.41  E-value: 8.94e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNqihCAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLpymrhg 1185
Cdd:cd13988      1 LGQGATANVFRGRHKKTGDL---YAVKVFNNLSFMRPLDVQMREFEVLKKLNHKNIVKLFAIEEELTTRHKVLV------ 71
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 dllrfirspqrvsaqcpgwgvsasTHLCRCSPVSSCPQNPTVkdliSFGL----------QVACGMEYLAEQKFVHRDLA 1255
Cdd:cd13988     72 ------------------------MELCPCGSLYTVLEEPSN----AYGLpeseflivlrDVVAGMNHLRENGIVHRDIK 123
                          170       180       190
                   ....*....|....*....|....*....|...
gi 2678964124 1256 ARNCML---DESFTV-KVADFGLARGILDKEYY 1284
Cdd:cd13988    124 PGNIMRvigEDGQSVyKLTDFGAARELEDDEQF 156
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
1106-1275 9.24e-06

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: 49.19  E-value: 9.24e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEaqnQIHCAIKSLSRITEVQE-------------------------VEAFLREGLIMRGLHHPN 1160
Cdd:cd14199     10 IGKGSYGVVKLAYNEDD---NTYYAMKVLSKKKLMRQagfprrppprgaraapegctqprgpIERVYQEIAILKKLDHPN 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1161 ILALIGIMLPPEGlprvllpymrhgDLLRFIrspqrvsaqcpgwgvsasTHLCRCSPVSSCPQ-NPTVKDLISFGLQ-VA 1238
Cdd:cd14199     87 VVKLVEVLDDPSE------------DHLYMV------------------FELVKQGPVMEVPTlKPLSEDQARFYFQdLI 136
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 2678964124 1239 CGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14199    137 KGIEYLHYQKIIHRDVKPSNLLVGEDGHIKIADFGVS 173
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
1104-1299 9.48e-06

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: 49.56  E-value: 9.48e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgeYTDEAQNQIHCAIKSLSRI--TEVQEVEAFlREGLIMRGLHHPNILALIGIMLPPEGLPR----- 1176
Cdd:cd07880     21 KQVGSGAYGTVC---SALDRRTGAKVAIKKLYRPfqSELFAKRAY-RELRLLKHMKHENVIGLLDVFTPDLSLDRfhdfy 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1177 VLLPYMrhGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptvKDLISFGL-QVACGMEYLAEQKFVHRDLA 1255
Cdd:cd07880     97 LVMPFM--GTDLGKLMKHEKLS-----------------------------EDRIQFLVyQMLKGLKYIHAAGIIHRDLK 145
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 2678964124 1256 ARNCMLDESFTVKVADFGLARGIlDKE---YYSVRQHRHARLPVKWM 1299
Cdd:cd07880    146 PGNLAVNEDCELKILDFGLARQT-DSEmtgYVVTRWYRAPEVILNWM 191
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
1106-1275 1.01e-05

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: 48.60  E-value: 1.01e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFG--VVYHGEYTDEAqnqihCAIKSLSRIT---------------EVQEVEAFlREGLIMRGLHHPNILALIGIM 1168
Cdd:cd14077      9 IGAGSMGkvKLAKHIRTGEK-----CAIKIIPRASnaglkkerekrlekeISRDIRTI-REAALSSLLNHPHICRLRDFL 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1169 LPPEGLpRVLLPYMRHGDLLRFIRSPQRVSAqcpgwgvsastHLCRcspvsscpqnptvkdliSFGLQVACGMEYLAEQK 1248
Cdd:cd14077     83 RTPNHY-YMLFEYVDGGQLLDYIISHGKLKE-----------KQAR-----------------KFARQIASALDYLHRNS 133
                          170       180
                   ....*....|....*....|....*..
gi 2678964124 1249 FVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14077    134 IVHRDLKIENILISKSGNIKIIDFGLS 160
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
1104-1298 1.08e-05

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: 49.11  E-value: 1.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGeyTDEAQNQiHCAIKSLSR--ITEVQEVEAFlREGLIMRGLHHPNILALIGIMLPP-EGLprVLLP 1180
Cdd:cd07856     16 QPVGMGAFGLVCSA--RDQLTGQ-NVAVKKIMKpfSTPVLAKRTY-RELKLLKHLRHENIISLSDIFISPlEDI--YFVT 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSpqrvsaqcpgwgvsasthlcrcspvsscpqNPTVKDLISFGL-QVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd07856     90 ELLGTDLHRLLTS------------------------------RPLEKQFIQYFLyQILRGLKYVHSAGVIHRDLKPSNI 139
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 2678964124 1260 MLDESFTVKVADFGLARgILDKE---YYSVRQHRHARLPVKW 1298
Cdd:cd07856    140 LVNENCDLKICDFGLAR-IQDPQmtgYVSTRYYRAPEIMLTW 180
STKc_PDIK1L cd13977
Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs ...
1104-1290 1.10e-05

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L 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: 270879 [Multi-domain]  Cd Length: 322  Bit Score: 49.09  E-value: 1.10e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgeytdEA---QNQIHCAIKSLsRITEVQEVEAFLREGLIMRGL--HHPNILALIGIMLPPEGLPRVL 1178
Cdd:cd13977      6 REVGRGSYGVVY------EAvvrRTGARVAVKKI-RCNAPENVELALREFWALSSIqrQHPNVIQLEECVLQRDGLAQRM 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 LPYMRHGDL-LRFIRSP---QRVSAQCPGWGVSASTHLCRCSPVSS--CPQNPTVKDLISFGLQVACGMEYLAEQKFVHR 1252
Cdd:cd13977     79 SHGSSKSDLyLLLVETSlkgERCFDPRSACYLWFVMEFCDGGDMNEylLSRRPDRQTNTSFMLQLSSALAFLHRNQIVHR 158
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 2678964124 1253 DLAARNCMLDESF---TVKVADFGLAR-----GILDKEYYSVRQHR 1290
Cdd:cd13977    159 DLKPDNILISHKRgepILKVADFGLSKvcsgsGLNPEEPANVNKHF 204
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
1106-1275 1.19e-05

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: 48.60  E-value: 1.19e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeyTDEAQNQIhCAIKSLSrITEVQEVEAF---LREGLIMRGLHHPNILALIGIMLPpEGLPRVLLPYM 1182
Cdd:cd06607      9 IGHGSFGAVYYA--RNKRTSEV-VAIKKMS-YSGKQSTEKWqdiIKEVKFLRQLRHPNTIEYKGCYLR-EHTAWLVMEYC 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 --RHGDLLRFIRSPQR---VSAQCPGwgvsasthlcrcspvsscpqnptvkdlisfGLQvacGMEYLAEQKFVHRDLAAR 1257
Cdd:cd06607     84 lgSASDIVEVHKKPLQeveIAAICHG------------------------------ALQ---GLAYLHSHNRIHRDVKAG 130
                          170
                   ....*....|....*...
gi 2678964124 1258 NCMLDESFTVKVADFGLA 1275
Cdd:cd06607    131 NILLTEPGTVKLADFGSA 148
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
1236-1314 1.27e-05

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: 48.51  E-value: 1.27e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1236 QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEyySVRqhrhARL-PVKWMALESLQTYRFTTKSD 1314
Cdd:cd05605    110 EITCGLEHLHSERIVYRDLKPENILLDDHGHVRISDLGLAVEIPEGE--TIR----GRVgTVGYMAPEVVKNERYTFSPD 183
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
1144-1315 1.30e-05

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: 48.28  E-value: 1.30e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1144 EAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlpymrhgdllrfirspQRVSAQCpgwgvsaSTHLCRCSPVSSCpq 1223
Cdd:cd14156     33 HKIVREISLLQKLSHPNIVRYLGICVKDEKLHPIL----------------EYVSGGC-------LEELLAREELPLS-- 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1224 nptVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVK---VADFGLARGILDKEYYSVRQHRHARLPVKWMA 1300
Cdd:cd14156     88 ---WREKVELACDISRGMVYLHSKNIYHRDLNSKNCLIRVTPRGReavVTDFGLAREVGEMPANDPERKLSLVGSAFWMA 164
                          170
                   ....*....|....*
gi 2678964124 1301 LESLQTYRFTTKSDV 1315
Cdd:cd14156    165 PEMLRGEPYDRKVDV 179
IPT smart00429
ig-like, plexins, transcription factors;
795-856 1.35e-05

ig-like, plexins, transcription factors;


Pssm-ID: 214657 [Multi-domain]  Cd Length: 90  Bit Score: 44.72  E-value: 1.35e-05
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124   795 DPIVLDISPKCGY--SGSHVMVHGQHLTSAWHLTVSFNDGqsivESRCAGQFLEQQHQ-CRLPEY 856
Cdd:smart00429    1 DPVITRISPTSGPvsGGTEITLCGKNLKSISVVFVEVGVG----EAPCTFSPSSSTAIvCKTPPY 61
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
1104-1274 1.73e-05

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 48.51  E-value: 1.73e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEytdEAQNQIHCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd05571      1 KVLGKGTFGKVILCR---EKATGELYAIKILKKevIIAKDEVAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVM-EY 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLrfirspqrvsaqcpgwgvsasTHLCRCSPVSscpqnptvKDLISF-GLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05571     77 VNGGELF---------------------FHLSRERVFS--------EDRTRFyGAEIVLALGYLHSQGIVYRDLKLENLL 127
                          170
                   ....*....|....
gi 2678964124 1261 LDESFTVKVADFGL 1274
Cdd:cd05571    128 LDKDGHIKITDFGL 141
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
1106-1299 1.97e-05

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: 48.51  E-value: 1.97e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNqihCAIKSLSR-ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPP---EGLPRVLLPY 1181
Cdd:cd07878     23 VGSGAYGSVCSAYDTRLRQK---VAVKKLSRpFQSLIHARRTYRELRLLKHMKHENVIGLLDVFTPAtsiENFNEVYLVT 99
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptvKDLISFGL-QVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd07878    100 NLMGADLNNIVKCQKLS-----------------------------DEHVQFLIyQLLRGLKYIHSAGIIHRDLKPSNVA 150
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 2678964124 1261 LDESFTVKVADFGLARGILDKE--YYSVRQHRHARLPVKWM 1299
Cdd:cd07878    151 VNEDCELRILDFGLARQADDEMtgYVATRWYRAPEIMLNWM 191
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
1105-1276 2.07e-05

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: 47.77  E-value: 2.07e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEytDEAQNQIHcAIK--SLSRITEvQEVEAFLREGLIMRGLHHPNILA-----LIGIMLPpeglprV 1177
Cdd:cd08530      7 KLGKGSYGSVYKVK--RLSDNQVY-ALKevNLGSLSQ-KEREDSVNEIRLLASVNHPNIIRykeafLDGNRLC------I 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHGDLLRFIRSPQRVsaqcpgwgvsasthlcrcspvsscpQNPTVKDLI-SFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd08530     77 VMEYAPFGDLSKLISKRKKK-------------------------RRLFPEDDIwRIFIQMLRGLKALHDQKILHRDLKS 131
                          170       180
                   ....*....|....*....|
gi 2678964124 1257 RNCMLDESFTVKVADFGLAR 1276
Cdd:cd08530    132 ANILLSAGDLVKIGDLGISK 151
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
1105-1276 2.20e-05

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: 47.78  E-value: 2.20e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVyhgEYTDEAQNQIHCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYM 1182
Cdd:cd14209      8 TLGTGSFGRV---MLVRHKETGNYYAMKILDKqkVVKLKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVM-EYV 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVSAQcpgwgvsastHlCRCspvsscpqnptvkdlisFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd14209     84 PGGEMFSHLRRIGRFSEP----------H-ARF-----------------YAAQIVLAFEYLHSLDLIYRDLKPENLLID 135
                          170
                   ....*....|....
gi 2678964124 1263 ESFTVKVADFGLAR 1276
Cdd:cd14209    136 QQGYIKVTDFGFAK 149
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
1095-1275 2.66e-05

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: 47.33  E-value: 2.66e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1095 HEQVVihtdQVIGKGHFGVVYhgeytdEAQNQ---IHCAIKSLSrITEVQEVEAFLREGLIMRGL-HHPNILaligimlp 1170
Cdd:cd13985      1 RYQVT----KQLGEGGFSYVY------LAHDVntgRRYALKRMY-FNDEEQLRVAIKEIEIMKRLcGHPNIV-------- 61
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1171 peglprvllPYMRHGdllrFIRSPqrvsaqcPGWGVSASTHLCRCSPV---SSCPQNP-TVKDLISFGLQVACGMEYLAE 1246
Cdd:cd13985     62 ---------QYYDSA----ILSSE-------GRKEVLLLMEYCPGSLVdilEKSPPSPlSEEEVLRIFYQICQAVGHLHS 121
                          170       180       190
                   ....*....|....*....|....*....|.
gi 2678964124 1247 QK--FVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd13985    122 QSppIIHRDIKIENILFSNTGRFKLCDFGSA 152
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
1104-1276 2.70e-05

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: 47.76  E-value: 2.70e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDeaqNQIHCAIKSLSR--ITEVQEVEAFLREGLIMR-GLHHPNILALIGIMLPPEGLPRVLlP 1180
Cdd:cd05592      1 KVLGKGSFGKVMLAELKG---TNQYFAIKALKKdvVLEDDDVECTMIERRVLAlASQHPFLTHLFCTFQTESHLFFVM-E 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptvKDLISF-GLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd05592     77 YLNGGDLMFHIQQSGRFD-----------------------------EDRARFyGAEIICGLQFLHSRGIIYRDLKLDNV 127
                          170
                   ....*....|....*..
gi 2678964124 1260 MLDESFTVKVADFGLAR 1276
Cdd:cd05592    128 LLDREGHIKIADFGMCK 144
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
1106-1276 2.85e-05

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: 47.51  E-value: 2.85e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYtdeaQNQIHcAIKSLSRITEVQEV---EAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLpYM 1182
Cdd:cd14159      1 IGEGGFGCVYQAVM----RNTEY-AVKRLKEDSELDWSvvkNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYV-YL 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRvsaqcpgwgvsasthlcrcSPVSSCPQNptvkdlISFGLQVACGMEYLAEQK--FVHRDLAARNCM 1260
Cdd:cd14159     75 PNGSLEDRLHCQVS-------------------CPCLSWSQR------LHVLLGTARAIQYLHSDSpsLIHGDVKSSNIL 129
                          170
                   ....*....|....*.
gi 2678964124 1261 LDESFTVKVADFGLAR 1276
Cdd:cd14159    130 LDAALNPKLGDFGLAR 145
STKc_JNK1 cd07875
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the ...
1106-1276 2.94e-05

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143380 [Multi-domain]  Cd Length: 364  Bit Score: 48.12  E-value: 2.94e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEytdEAQNQIHCAIKSLSRITEVQ-EVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMrh 1184
Cdd:cd07875     32 IGSGAQGIVCAAY---DAILERNVAIKKLSRPFQNQtHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYI-- 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1185 gdLLRFIrspqrvsaqcpgwgvsaSTHLCRCSpvsscpQNPTVKDLISFGL-QVACGMEYLAEQKFVHRDLAARNCMLDE 1263
Cdd:cd07875    107 --VMELM-----------------DANLCQVI------QMELDHERMSYLLyQMLCGIKHLHSAGIIHRDLKPSNIVVKS 161
                          170
                   ....*....|...
gi 2678964124 1264 SFTVKVADFGLAR 1276
Cdd:cd07875    162 DCTLKILDFGLAR 174
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
1130-1299 3.03e-05

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: 47.97  E-value: 3.03e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1130 AIKSLSRI--TEVQEVEAFlREGLIMRGLHHPNILALIGIMLPPEGLPR-----VLLPYMRhGDLlrfirspQRVSAQcp 1202
Cdd:cd07879     44 AIKKLSRPfqSEIFAKRAY-RELTLLKHMQHENVIGLLDVFTSAVSGDEfqdfyLVMPYMQ-TDL-------QKIMGH-- 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1203 gwgvsasthlcrcspvsscpqnPTVKDLISFGL-QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGIlDK 1281
Cdd:cd07879    113 ----------------------PLSEDKVQYLVyQMLCGLKYIHSAGIIHRDLKPGNLAVNEDCELKILDFGLARHA-DA 169
                          170       180
                   ....*....|....*....|.
gi 2678964124 1282 E---YYSVRQHRHARLPVKWM 1299
Cdd:cd07879    170 EmtgYVVTRWYRAPEVILNWM 190
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
1236-1275 3.06e-05

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: 47.00  E-value: 3.06e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2678964124 1236 QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14004    117 QVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSA 156
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
1226-1276 3.09e-05

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: 47.33  E-value: 3.09e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2678964124 1226 TVKDLIsfgLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd07862    111 TIKDMM---FQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLAR 158
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1104-1276 3.69e-05

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: 47.05  E-value: 3.69e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEY-TDEAQNqihcAIKSLS-RITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPY 1181
Cdd:cd08223      6 RVIGKGSYGEVWLVRHkRDRKQY----VIKKLNlKNASKRERKAAEQEAKLLSKLKHPNIVSYKESFEGEDGFLYIVMGF 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLRFIRSPQRVsaqcpgwgvsasthlcrcsPVSScpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd08223     82 CEGGDLYTRLKEQKGV-------------------LLEE-------RQVVEWFVQIAMALQYMHERNILHRDLKTQNIFL 135
                          170
                   ....*....|....*
gi 2678964124 1262 DESFTVKVADFGLAR 1276
Cdd:cd08223    136 TKSNIIKVGDLGIAR 150
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
1106-1275 3.70e-05

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: 47.33  E-value: 3.70e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgeytdEAQNQ---IHCAIKSLSRITEvQEVEAFLREGLIMRGLHHPNILALIGimlppeglprvllPYM 1182
Cdd:cd06644     20 LGDGAFGKVY------KAKNKetgALAAAKVIETKSE-EELEDYMVEIEILATCNHPYIVKLLG-------------AFY 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSpqrvsaqCPGWGVSASThlcrcSPVSSCPQNPTVKDLISfglQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd06644     80 WDGKLWIMIEF-------CPGGAVDAIM-----LELDRGLTEPQIQVICR---QMLEALQYLHSMKIIHRDLKAGNVLLT 144
                          170
                   ....*....|...
gi 2678964124 1263 ESFTVKVADFGLA 1275
Cdd:cd06644    145 LDGDIKLADFGVS 157
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
1231-1314 3.76e-05

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: 47.29  E-value: 3.76e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1231 ISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEyySVRqhrhARL-PVKWMALESLQTYRF 1309
Cdd:cd05631    105 IFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAVQIPEGE--TVR----GRVgTVGYMAPEVINNEKY 178

                   ....*
gi 2678964124 1310 TTKSD 1314
Cdd:cd05631    179 TFSPD 183
PSI pfam01437
Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The ...
552-594 3.83e-05

Plexin repeat; A cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found Plexin. Two copies of the repeat are found in mahogany protein. A related C. elegans protein contains four copies of the repeat. The Met receptor contains a single copy of the repeat. The Pfam alignment shows 6 conserved cysteine residues that may form three conserved disulphide bridges, whereas some members show 8 conserved cysteines. The pattern of conservation suggests that cysteines 5 and 7 (that are not absolutely conserved) form a disulphide bridge (Personal observation. A Bateman).


Pssm-ID: 396154 [Multi-domain]  Cd Length: 52  Bit Score: 42.31  E-value: 3.83e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124  552 GCGHFLTCWRCLRAqRFMGCGWCGD--RCGRQKECPG------SWQQD--YCP 594
Cdd:pfam01437    1 RCSQYTSCSSCLAA-RDPYCGWCSSegRCVRRSACGApegnceEWEQAssKCP 52
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
1233-1276 4.06e-05

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: 46.93  E-value: 4.06e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2678964124 1233 FGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd07871    108 FMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLAR 151
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
1231-1314 4.10e-05

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: 46.94  E-value: 4.10e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1231 ISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYSVRQHrharlPVKWMALESLQTYRFT 1310
Cdd:cd05630    105 VFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAVHVPEGQTIKGRVG-----TVGYMAPEVVKNERYT 179

                   ....
gi 2678964124 1311 TKSD 1314
Cdd:cd05630    180 FSPD 183
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
1104-1280 4.46e-05

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: 47.31  E-value: 4.46e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgeYTDEAQNQIHCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd05595      1 KLLGKGTFGKVI---LVREKATGRYYAMKILRKevIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVM-EY 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLrFIRSPQRVSAQcpgwgvsasthlcrcspvsscpqnptvkDLISF-GLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05595     77 ANGGELF-FHLSRERVFTE----------------------------DRARFyGAEIVSALEYLHSRDVVYRDIKLENLM 127
                          170       180
                   ....*....|....*....|.
gi 2678964124 1261 LDESFTVKVADFGLAR-GILD 1280
Cdd:cd05595    128 LDKDGHIKITDFGLCKeGITD 148
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
1229-1275 4.61e-05

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: 46.75  E-value: 4.61e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2678964124 1229 DLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd05577     96 RAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLA 142
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
1106-1275 4.64e-05

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: 46.73  E-value: 4.64e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQNqihCAIKSLSRITEVQE---VEAFLREGLIMRGLHHPNILALIGImLPPEGLPRVLLPYM 1182
Cdd:cd14070     10 LGEGSFAKVREGLHAVTGEK---VAIKVIDKKKAKKDsyvTKNLRREGRIQQMIRHPNITQLLDI-LETENSYYLVMELC 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVSAqcpgwgvsasthlcrcspvsscpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd14070     86 PGGNLMHRIYDKKRLEE----------------------------REARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLD 137
                          170
                   ....*....|...
gi 2678964124 1263 ESFTVKVADFGLA 1275
Cdd:cd14070    138 ENDNIKLIDFGLS 150
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
1102-1286 4.80e-05

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: 46.45  E-value: 4.80e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1102 TDQVIGKGHFGVVYHGEYTDE----AQNQIHcaIKSLSRitevQEVEAFLREGLIMRGLHHPNILALIG---------IM 1168
Cdd:cd13983      5 FNEVLGRGSFKTVYRAFDTEEgievAWNEIK--LRKLPK----AERQRFKQEIEILKSLKHPNIIKFYDsweskskkeVI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1169 LPPEglprvllpYMRHGDLLRFIRspqRVsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYL--AE 1246
Cdd:cd13983     79 FITE--------LMTSGTLKQYLK---RF-------------------------KRLKLKVIKSWCRQILEGLNYLhtRD 122
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 2678964124 1247 QKFVHRDLAARNCMLDESF-TVKVADFGLARGILDKEYYSV 1286
Cdd:cd13983    123 PPIIHRDLKCDNIFINGNTgEVKIGDLGLATLLRQSFAKSV 163
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
1147-1276 5.11e-05

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: 46.61  E-value: 5.11e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1147 LREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPYMrHGDLLRFIRspqrvsaQCPGwGVSasthlcrcspvsscPQNpt 1226
Cdd:cd07844     46 IREASLLKDLKHANIVTLHDIIHTKKTLTLVF-EYL-DTDLKQYMD-------DCGG-GLS--------------MHN-- 99
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1227 VKdliSFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd07844    100 VR---LFLFQLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLAR 146
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
1106-1283 5.24e-05

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 47.12  E-value: 5.24e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEAQnqiHCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALI-GIMlpPEGLPRVLLPYM 1182
Cdd:PTZ00263    26 LGTGSFGRVRIAKHKGTGE---YYAIKCLKKreILKMKQVQHVAQEKSILMELSHPFIVNMMcSFQ--DENRVYFLLEFV 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSPQRVSaqcpgwgvsasthlcrcspvsscpqnptvKDLISF-GLQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:PTZ00263   101 VGGELFTHLRKAGRFP-----------------------------NDVAKFyHAELVLAFEYLHSKDIIYRDLKPENLLL 151
                          170       180
                   ....*....|....*....|..
gi 2678964124 1262 DESFTVKVADFGLARGILDKEY 1283
Cdd:PTZ00263   152 DNKGHVKVTDFGFAKKVPDRTF 173
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
1105-1275 5.36e-05

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: 46.39  E-value: 5.36e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVYHGEYTDEAQNqihCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGiMLPPEGLPRVLLPYM 1182
Cdd:cd14186      8 LLGKGSFACVYRARSLHTGLE---VAIKMIDKkaMQKAGMVQRVRNEVEIHCQLKHPSILELYN-YFEDSNYVYLVLEMC 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLLRFIRSpqrvsaqcpgwgvsasthlcRCSPVSScpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd14186     84 HNGEMSRYLKN--------------------RKKPFTE-------DEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLT 136
                          170
                   ....*....|...
gi 2678964124 1263 ESFTVKVADFGLA 1275
Cdd:cd14186    137 RNMNIKIADFGLA 149
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
1106-1274 5.60e-05

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 46.75  E-value: 5.60e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeYTDEAQNqihcAIKSLSRI--TEVQEVEAFLR-EGLIMRGLHHPNILALIGIMLPPEgLPRVLLPYM 1182
Cdd:cd14157      1 ISEGTFADIYKG-YRHGKQY----VIKRLKETecESPKSTERFFQtEVQICFRCCHPNILPLLGFCVESD-CHCLIYPYM 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1183 RHGDLlrfirspqRVSAQCPGwgvsasthlcrcspvSSCPQNPTVKDLISFGLqvACGMEYLAEQKFVHRDLAARNCMLD 1262
Cdd:cd14157     75 PNGSL--------QDRLQQQG---------------GSHPLPWEQRLSISLGL--LKAVQHLHNFGILHGNIKSSNVLLD 129
                          170
                   ....*....|..
gi 2678964124 1263 ESFTVKVADFGL 1274
Cdd:cd14157    130 GNLLPKLGHSGL 141
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
1148-1276 5.70e-05

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 47.13  E-value: 5.70e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1148 REGLIMRGLHHPNILALIGiMLPPEGLPRVLLPYMRHGDLlrfirspqrvsaqcpgwgvsASTHLCrcspvsscpQNPTV 1227
Cdd:PLN00034   121 REIEILRDVNHPNVVKCHD-MFDHNGEIQVLLEFMDGGSL--------------------EGTHIA---------DEQFL 170
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2678964124 1228 KDLisfGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:PLN00034   171 ADV---ARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSR 216
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
1105-1315 6.62e-05

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: 46.19  E-value: 6.62e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1105 VIGKGHFGVVY--HGEYT--DEAQNQIH-CAIKSLSRitevQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLL 1179
Cdd:cd06625      7 LLGQGAFGQVYlcYDADTgrELAVKQVEiDPINTEAS----KEVKALECEIQLLKNLQHERIVQYYGCLQDEKSL-SIFM 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIRspqrvsaqcpgwgvsasTHLCRCSPVSSCpqnptvkdlisFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd06625     82 EYMPGGSVKDEIK-----------------AYGALTENVTRK-----------YTRQILEGLAYLHSNMIVHRDIKGANI 133
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1260 MLDESFTVKVADFGLArgildKEYYSVRQHRHARlPVK----WMALESLQTYRFTTKSDV 1315
Cdd:cd06625    134 LRDSNGNVKLGDFGAS-----KRLQTICSSTGMK-SVTgtpyWMSPEVINGEGYGRKADI 187
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
1104-1315 7.13e-05

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: 46.28  E-value: 7.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGeYTDEAQ----NQIhcAIKSLSRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEglprVLL 1179
Cdd:cd06631      7 NVLGKGAYGTVYCG-LTSTGQliavKQV--ELDTSDKEKAEKEYEKLQEEVDLLKTLKHVNIVGYLGTCLEDN----VVS 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRhgdllrFIrspqrvsaqcPGWgvSASTHLCRCSPVSScpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNC 1259
Cdd:cd06631     80 IFME------FV----------PGG--SIASILARFGALEE-------PVFCRYTKQILEGVAYLHNNNVIHRDIKGNNI 134
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2678964124 1260 MLDESFTVKVADFGLAR--GILDKEYYSVRQHRHARLPVKWMALESLQTYRFTTKSDV 1315
Cdd:cd06631    135 MLMPNGVIKLIDFGCAKrlCINLSSGSQSQLLKSMRGTPYWMAPEVINETGHGRKSDI 192
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
1106-1276 7.62e-05

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: 46.06  E-value: 7.62e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGEYTDEaqnQIHCAIKSLSRITEVQEVE--AFLREGLIMRGLHHPNILALIGIMLPPEGLPrVLLPYMR 1183
Cdd:cd14026      5 LSRGAFGTVSRARHADW---RVTVAIKCLKLDSPVGDSErnCLLKEAEILHKARFSYILPILGICNEPEFLG-IVTEYMT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 HGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGL--QVACGMEYLAEQK--FVHRDLAARNC 1259
Cdd:cd14026     81 NGSLNELLHEKD---------------------------IYPDVAWPLRLRIlyEIALGVNYLHNMSppLLHHDLKTQNI 133
                          170
                   ....*....|....*..
gi 2678964124 1260 MLDESFTVKVADFGLAR 1276
Cdd:cd14026    134 LLDGEFHVKIADFGLSK 150
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
1106-1276 8.01e-05

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 46.35  E-value: 8.01e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGE--YTDEaqnqihcaIKSLSRITEVQEVEAF----LREGLIMRGLHHPNILALIGIMLPPEGLPRVL- 1178
Cdd:PLN00009    10 IGEGTYGVVYKARdrVTNE--------TIALKKIRLEQEDEGVpstaIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFe 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1179 ---LPYMRHGDllrfirspqrvsaQCPGWGvsasthlcrcspvsscpQNPTVkdLISFGLQVACGMEYLAEQKFVHRDLA 1255
Cdd:PLN00009    82 yldLDLKKHMD-------------SSPDFA-----------------KNPRL--IKTYLYQILRGIAYCHSHRVLHRDLK 129
                          170       180
                   ....*....|....*....|..
gi 2678964124 1256 ARNCMLDESF-TVKVADFGLAR 1276
Cdd:PLN00009   130 PQNLLIDRRTnALKLADFGLAR 151
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
1224-1314 8.05e-05

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: 46.12  E-value: 8.05e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1224 NPTVKD--LISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEyySVRqhrhARL-PVKWMA 1300
Cdd:cd05632     98 NPGFEEerALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKIPEGE--SIR----GRVgTVGYMA 171
                           90
                   ....*....|....
gi 2678964124 1301 LESLQTYRFTTKSD 1314
Cdd:cd05632    172 PEVLNNQRYTLSPD 185
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
1130-1276 9.03e-05

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. 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. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 46.23  E-value: 9.03e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1130 AIKSLSRITEVQ-EVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMrhgdLLRFIrspqrvsaqcpgwgvsa 1208
Cdd:cd07874     46 AIKKLSRPFQNQtHAKRAYRELVLMKCVNHKNIISLLNVFTPQKSLEEFQDVYL----VMELM----------------- 104
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1209 STHLCRCSpvsscpQNPTVKDLISFGL-QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd07874    105 DANLCQVI------QMELDHERMSYLLyQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLAR 167
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
1212-1275 9.23e-05

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


Pssm-ID: 271102 [Multi-domain]  Cd Length: 284  Bit Score: 46.10  E-value: 9.23e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2678964124 1212 LCRCSPVSSCP-QNPTVKDLISFGLQ-VACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14200    106 LLRKGPVMEVPsDKPFSEDQARLYFRdIVLGIEYLHYQKIVHRDIKPSNLLLGDDGHVKIADFGVS 171
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
1104-1294 1.03e-04

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: 46.12  E-value: 1.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgEYTDEAQNQIhCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd05573      7 KVIGRGAFGEVW--LVRDKDTGQV-YAMKILRKsdMLKREQIAHVRAERDILADADSPWIVRLHYAFQDEDHLYLVM-EY 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLrfirspqrvsaqcpgwgvsasTHLCRcspvSSCPQNPTVKDLISfglQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd05573     83 MPGGDLM---------------------NLLIK----YDVFPEETARFYIA---ELVLALDSLHKLGFIHRDIKPDNILL 134
                          170       180       190
                   ....*....|....*....|....*....|....
gi 2678964124 1262 DESFTVKVADFGLARGILD-KEYYSVRQHRHARL 1294
Cdd:cd05573    135 DADGHIKLADFGLCTKMNKsGDRESYLNDSVNTL 168
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
1233-1277 1.20e-04

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: 45.76  E-value: 1.20e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2678964124 1233 FGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARG 1277
Cdd:cd07873    105 FLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARA 149
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
1231-1315 1.26e-04

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: 45.46  E-value: 1.26e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1231 ISFGLQVACGMEYLAEQKF-VHRDLAARNCMLDESFTVKVADFGLaRGILDKEyySVRQHRHARLPVK--WMALESLQTY 1307
Cdd:cd13992    100 SSFIKDIVKGMNYLHSSSIgYHGRLKSSNCLVDSRWVVKLTDFGL-RNLLEEQ--TNHQLDEDAQHKKllWTAPELLRGS 176
                           90
                   ....*....|..
gi 2678964124 1308 ----RFTTKSDV 1315
Cdd:cd13992    177 llevRGTQKGDV 188
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
1104-1315 1.30e-04

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: 45.11  E-value: 1.30e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgeYTDEAQNQIHCAIKSLSRIT--EVQEVEAF--LREGLIMRGLHHPNILALIGIMLPPEGLPrVLL 1179
Cdd:cd08222      6 RKLGSGNFGTVY---LVSDLKATADEELKVLKEISvgELQPDETVdaNREAKLLSKLDHPAIVKFHDSFVEKESFC-IVT 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLlrfirspqrvsaqcpgwgvsasthlcrCSPVSSCPQNPTVKD---LISFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd08222     82 EYCEGGDL---------------------------DDKISEYKKSGTTIDenqILDWFIQLLLAVQYMHERRILHRDLKA 134
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1257 RNCMLDESFtVKVADFGLAR---GILD-------KEYYsvrqhrharlpvkwMALESLQTYRFTTKSDV 1315
Cdd:cd08222    135 KNIFLKNNV-IKVGDFGISRilmGTSDlattftgTPYY--------------MSPEVLKHEGYNSKSDI 188
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
1143-1283 1.38e-04

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: 45.42  E-value: 1.38e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1143 VEAFLREGLIMRGLH-HPNILALIGIMLPPEGLPRVLlPYMRHGDLLRFIRSPQRVSAQcpgwgvsaSTHLcrcspvssc 1221
Cdd:cd14093     52 REATRREIEILRQVSgHPNIIELHDVFESPTFIFLVF-ELCRKGELFDYLTEVVTLSEK--------KTRR--------- 113
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1222 pqnpTVKDLISfglqvacGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEY 1283
Cdd:cd14093    114 ----IMRQLFE-------AVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEGEK 164
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
1101-1273 1.75e-04

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: 44.79  E-value: 1.75e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1101 HTDQVIGKGHFGVVYhgeYTDEAQNQIHCAIKSLSRITEVQEVEAFLrEGLIMRGL-HHPNILALIGIMLPPE----GLP 1175
Cdd:cd13975      3 KLGRELGRGQYGVVY---ACDSWGGHFPCALKSVVPPDDKHWNDLAL-EFHYTRSLpKHERIVSLHGSVIDYSygggSSI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1176 RVLLPYMR-HGDLLRFIRSpqrvsaqcpgwgvsasthlcrcspvsscpqNPTVKDLISFGLQVACGMEYLAEQKFVHRDL 1254
Cdd:cd13975     79 AVLLIMERlHRDLYTGIKA------------------------------GLSLEERLQIALDVVEGIRFLHSQGLVHRDI 128
                          170
                   ....*....|....*....
gi 2678964124 1255 AARNCMLDESFTVKVADFG 1273
Cdd:cd13975    129 KLKNVLLDKKNRAKITDLG 147
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
1104-1280 2.26e-04

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: 45.07  E-value: 2.26e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgeYTDEAQNQIHCAIKSLSR--ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLlPY 1181
Cdd:cd05593     21 KLLGKGTFGKVI---LVREKASGKYYAMKILKKevIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVM-EY 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MRHGDLLrFIRSPQRVSAQcpgwgvsasthlcrcspvsscpqnptvkDLISF-GLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd05593     97 VNGGELF-FHLSRERVFSE----------------------------DRTRFyGAEIVSALDYLHSGKIVYRDLKLENLM 147
                          170       180
                   ....*....|....*....|.
gi 2678964124 1261 LDESFTVKVADFGLAR-GILD 1280
Cdd:cd05593    148 LDKDGHIKITDFGLCKeGITD 168
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
1106-1281 2.80e-04

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: 44.36  E-value: 2.80e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVV--YHGEYTDEaqnqiHCAIKSLSRITEVQE--VEAFLREGLIMRGLHHPNILAliGIMLPPE-------GL 1174
Cdd:cd13989      1 LGSGGFGYVtlWKHQDTGE-----YVAIKKCRQELSPSDknRERWCLEVQIMKKLNHPNVVS--ARDVPPEleklspnDL 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1175 PRVLLPYMRHGDLLRFIRSPQrvsaQCPGWGVSasthlcrcspvsscpqnpTVKDLISfglQVACGMEYLAEQKFVHRDL 1254
Cdd:cd13989     74 PLLAMEYCSGGDLRKVLNQPE----NCCGLKES------------------EVRTLLS---DISSAISYLHENRIIHRDL 128
                          170       180       190
                   ....*....|....*....|....*....|
gi 2678964124 1255 AARNCMLDES---FTVKVADFGLARGiLDK 1281
Cdd:cd13989    129 KPENIVLQQGggrVIYKLIDLGYAKE-LDQ 157
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
1103-1315 3.03e-04

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: 43.84  E-value: 3.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1103 DQVIGKGHFGVVYhgEYTDEAQNQIHCAIKSLSRITEVQEVEAFLREGLIMRGLH-HPNILaligimlppeglprvllpy 1181
Cdd:cd14050      6 LSKLGEGSFGEVF--KVRSREDGKLYAVKRSRSRFRGEKDRKRKLEEVERHEKLGeHPNCV------------------- 64
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 mrhgdllRFIRS---PQRVSAQcpgwgvsasTHLCRCSPVSSCPQNPTV--KDLISFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd14050     65 -------RFIKAweeKGILYIQ---------TELCDTSLQQYCEETHSLpeSEVWNILLDLLKGLKHLHDHGLIHLDIKP 128
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2678964124 1257 RNCMLDESFTVKVADFGLARGiLDKEYYSVRQHRHARlpvkWMALESLQTyRFTTKSDV 1315
Cdd:cd14050    129 ANIFLSKDGVCKLGDFGLVVE-LDKEDIHDAQEGDPR----YMAPELLQG-SFTKAADI 181
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
1236-1278 3.35e-04

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: 44.15  E-value: 3.35e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2678964124 1236 QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGI 1278
Cdd:cd14187    115 QIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKV 157
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
1104-1276 3.69e-04

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: 44.33  E-value: 3.69e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYHGEYTDEAQNqihCAIKSLSR-ITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPR-----V 1177
Cdd:cd07850      6 KPIGSGAQGIVCAAYDTVTGQN---VAIKKLSRpFQNVTHAKRAYRELVLMKLVNHKNIIGLLNVFTPQKSLEEfqdvyL 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1178 LLPYMRHgdllrfirspqrvsaqcpgwgvsastHLCRCSpvsscpQNPTVKDLISFGL-QVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd07850     83 VMELMDA--------------------------NLCQVI------QMDLDHERMSYLLyQMLCGIKHLHSAGIIHRDLKP 130
                          170       180
                   ....*....|....*....|
gi 2678964124 1257 RNCMLDESFTVKVADFGLAR 1276
Cdd:cd07850    131 SNIVVKSDCTLKILDFGLAR 150
STKc_ACVR2b cd14140
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ...
1180-1275 4.30e-04

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: 43.87  E-value: 4.30e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIRSPQRVS-AQCPGWGVSASTHlcRCSPVSSCPQNP-TVKDLISFGLQVACGMEYLAEQ---------- 1247
Cdd:cd14140     44 PGMKHENLLQFIAAEKRGSnLEMELWLITAFHD--KGSLTDYLKGNIvSWNELCHIAETMARGLSYLHEDvprckgeghk 121
                           90       100
                   ....*....|....*....|....*....
gi 2678964124 1248 -KFVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14140    122 pAIAHRDFKSKNVLLKNDLTAVLADFGLA 150
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
1233-1277 4.51e-04

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: 43.83  E-value: 4.51e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2678964124 1233 FGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARG 1277
Cdd:cd07872    109 FLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARA 153
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
1148-1275 5.04e-04

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: 43.40  E-value: 5.04e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1148 REGLIMRGLHHPNILALIGIMLPPE-GLPRVLLPYMrHGDLLRFI-RSPQrvsAQCPGWgvsaSTHlcrcspvsscpqnp 1225
Cdd:cd14119     43 REIQILRRLNHRNVIKLVDVLYNEEkQKLYMVMEYC-VGGLQEMLdSAPD---KRLPIW----QAH-------------- 100
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1226 tvkdliSFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14119    101 ------GYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVA 144
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
1147-1276 5.70e-04

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 43.71  E-value: 5.70e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1147 LREGLIMRGLHHPNILALIGiMLPPEGLPRVLLPYMRhGDLLRFIRSpqrvsaqcpgwgvsasthlcRCSPVSscpqnpt 1226
Cdd:PHA03209   105 LIEAMLLQNVNHPSVIRMKD-TLVSGAITCMVLPHYS-SDLYTYLTK--------------------RSRPLP------- 155
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1227 VKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:PHA03209   156 IDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFINDVDQVCIGDLGAAQ 205
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
1233-1276 5.70e-04

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: 43.78  E-value: 5.70e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2678964124 1233 FGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd05620    101 YAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCK 144
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1235-1276 6.12e-04

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: 43.26  E-value: 6.12e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2678964124 1235 LQVACGMEYL-AEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd08528    120 VQMVLALRYLhKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAK 162
TIG pfam01833
IPT/TIG domain; This family consists of a domain that has an immunoglobulin like fold. These ...
595-651 6.33e-04

IPT/TIG domain; This family consists of a domain that has an immunoglobulin like fold. These domains are found in cell surface receptors such as Met and Ron as well as in intracellular transcription factors where it is involved in DNA binding. CAUTION: This family does not currently recognize a significant number of members.


Pssm-ID: 460355 [Multi-domain]  Cd Length: 84  Bit Score: 40.12  E-value: 6.33e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124  595 PEITEFHPHSGPLRGTTRLTLCGSNFYLRPDGVvpegthQITVGQSPCRLLPKDSST 651
Cdd:pfam01833    1 PVITSISPSSGPASGGTTITITGSNFGTDSSDL------KVTIGGTPCTVISVSSTT 51
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
1104-1275 6.72e-04

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: 43.19  E-value: 6.72e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYH----GEYTDEAQNQIHCAIKSLSRITEVqeVEAFLREGLIMRGLHHPNILALIGIMlppeglprvll 1179
Cdd:cd06630      6 PLLGTGAFSSCYQardvKTGTLMAVKQVSFCRNSSSEQEEV--VEAIREEIRMMARLNHPNIVRMLGAT----------- 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 pymRHGDLLR-FIRspqrvsaqcpgW--GVSASTHLCRCSPVSScpqnpTVkdLISFGLQVACGMEYLAEQKFVHRDLAA 1256
Cdd:cd06630     73 ---QHKSHFNiFVE-----------WmaGGSVASLLSKYGAFSE-----NV--IINYTLQILRGLAYLHDNQIIHRDLKG 131
                          170       180
                   ....*....|....*....|
gi 2678964124 1257 RNCMLDESFT-VKVADFGLA 1275
Cdd:cd06630    132 ANLLVDSTGQrLRIADFGAA 151
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
1127-1276 6.92e-04

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and 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. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 43.48  E-value: 6.92e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1127 IHCAIKSLSRITEVQ-EVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPRVLLPYMrhgdLLRFIrspqrvsaqcpgwg 1205
Cdd:cd07876     47 INVAVKKLSRPFQNQtHAKRAYRELVLLKCVNHKNIISLLNVFTPQKSLEEFQDVYL----VMELM-------------- 108
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2678964124 1206 vsaSTHLCRCSPVSscpqnpTVKDLISFGL-QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd07876    109 ---DANLCQVIHME------LDHERMSYLLyQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLAR 171
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
1106-1317 7.26e-04

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: 42.86  E-value: 7.26e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYhgEYTDEAQNQIHcAIKSLSRITE--VQEVEAFLReglimrgLHHPNILALIGIMLPPEGLPRvllpymr 1183
Cdd:cd14047     14 IGSGGFGQVF--KAKHRIDGKTY-AIKRVKLNNEkaEREVKALAK-------LDHPNIVRYNGCWDGFDYDPE------- 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1184 hgdllRFIRSPQRVSAQCpgwgVSASTHLCRCSPVSSC------PQNPTVKDLISFgLQVACGMEYLAEQKFVHRDLAAR 1257
Cdd:cd14047     77 -----TSSSNSSRSKTKC----LFIQMEFCEKGTLESWiekrngEKLDKVLALEIF-EQITKGVEYIHSKKLIHRDLKPS 146
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1258 NCMLDESFTVKVADFGLARGIldKEYYSVRQHRHARlpvKWMALESLQTYRFTTKSDVVP 1317
Cdd:cd14047    147 NIFLVDTGKVKIGDFGLVTSL--KNDGKRTKSKGTL---SYMSPEQISSQDYGKEVDIYA 201
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
1100-1276 8.55e-04

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: 42.59  E-value: 8.55e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1100 IHTDQVIGKGHFGVVYHGEytdEAQNQIHCAIKSLsRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLPrVLL 1179
Cdd:cd14193      6 VNKEEILGGGRFGQVHKCE---EKSSGLKLAAKII-KARSQKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIV-LVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1180 PYMRHGDLLRFIRSPQrvsaqcpgwgvsasthlcrcspvsscpQNPTVKDLISFGLQVACGMEYLAEQKFVHRDLAARN- 1258
Cdd:cd14193     81 EYVDGGELFDRIIDEN---------------------------YNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENi 133
                          170
                   ....*....|....*....
gi 2678964124 1259 -CMLDESFTVKVADFGLAR 1276
Cdd:cd14193    134 lCVSREANQVKIIDFGLAR 152
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
1241-1278 9.82e-04

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: 42.93  E-value: 9.82e-04
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2678964124 1241 MEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGI 1278
Cdd:cd07852    120 LKYLHSGGVIHRDLKPSNILLNSDCRVKLADFGLARSL 157
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
1106-1276 1.07e-03

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: 42.49  E-value: 1.07e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFG---VVYHGEytdeaqNQIHCAIK--SLSRItEVQEVEAFLREGLIMRGLHHPNILALIGiMLPPEGLPRVLLP 1180
Cdd:cd08218      8 IGEGSFGkalLVKSKE------DGKQYVIKeiNISKM-SPKEREESRKEVAVLSKMKHPNIVQYQE-SFEENGNLYIVMD 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1181 YMRHGDLLrfirspQRVSAQcpgWGVSASThlcrcspvsscpqnptvKDLISFGLQVACGMEYLAEQKFVHRDLAARNCM 1260
Cdd:cd08218     80 YCDGGDLY------KRINAQ---RGVLFPE-----------------DQILDWFVQLCLALKHVHDRKILHRDIKSQNIF 133
                          170
                   ....*....|....*.
gi 2678964124 1261 LDESFTVKVADFGLAR 1276
Cdd:cd08218    134 LTKDGIIKLGDFGIAR 149
STKc_Sid2p_like cd05600
Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the ...
1249-1282 1.15e-03

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270751 [Multi-domain]  Cd Length: 386  Bit Score: 43.10  E-value: 1.15e-03
                           10        20        30
                   ....*....|....*....|....*....|....
gi 2678964124 1249 FVHRDLAARNCMLDESFTVKVADFGLARGILDKE 1282
Cdd:cd05600    132 YIHRDLKPENFLIDSSGHIKLTDFGLASGTLSPK 165
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
1233-1280 1.31e-03

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 42.71  E-value: 1.31e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1233 FGLQVACGMEYL-AEQKFVHRDLAARNCMLDESFTVKVADFGLAR-GILD 1280
Cdd:cd05594    130 YGAEIVSALDYLhSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKeGIKD 179
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
1106-1315 1.42e-03

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: 42.40  E-value: 1.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1106 IGKGHFGVVYHGeyTDEAQNQiHCAIKSLSrITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLpRVLLPYMRHG 1185
Cdd:cd06654     28 IGQGASGTVYTA--MDVATGQ-EVAIRQMN-LQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDEL-WVVMEYLAGG 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1186 DLLRFirspqrVSAQCPGWGVSASthLCRcspvsSCPQnptvkdlisfglqvacGMEYLAEQKFVHRDLAARNCMLDESF 1265
Cdd:cd06654    103 SLTDV------VTETCMDEGQIAA--VCR-----ECLQ----------------ALEFLHSNQVIHRDIKSDNILLGMDG 153
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1266 TVKVADFGLARGILDKEyysVRQHRHARLPVkWMALESLQTYRFTTKSDV 1315
Cdd:cd06654    154 SVKLTDFGFCAQITPEQ---SKRSTMVGTPY-WMAPEVVTRKAYGPKVDI 199
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
1227-1301 1.46e-03

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: 42.20  E-value: 1.46e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1227 VKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKEYYSVR------------QHRHARL 1294
Cdd:cd05607    103 MERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLAVEVKEGKPITQRagtngymapeilKEESYSY 182

                   ....*..
gi 2678964124 1295 PVKWMAL 1301
Cdd:cd05607    183 PVDWFAM 189
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
1104-1275 1.59e-03

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: 41.84  E-value: 1.59e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1104 QVIGKGHFGVVYhgEYTDEAQNQIHcAIKSL--SRITEVQEVEAFLREGLIMRGLHHPNILALIGIMLPPEGLprvllpY 1181
Cdd:cd14189      7 RLLGKGGFARCY--EMTDLATNKTY-AVKVIphSRVAKPHQREKIVNEIELHRDLHHKHVVKFSHHFEDAENI------Y 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1182 MrhgdllrFIRSPQRVSaqcpgwgvsasthLCRCSPVSSCPQNPTVKDLISfglQVACGMEYLAEQKFVHRDLAARNCML 1261
Cdd:cd14189     78 I-------FLELCSRKS-------------LAHIWKARHTLLEPEVRYYLK---QIISGLKYLHLKGILHRDLKLGNFFI 134
                          170
                   ....*....|....
gi 2678964124 1262 DESFTVKVADFGLA 1275
Cdd:cd14189    135 NENMELKVGDFGLA 148
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
1236-1282 1.60e-03

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270759 [Multi-domain]  Cd Length: 288  Bit Score: 42.18  E-value: 1.60e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2678964124 1236 QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKE 1282
Cdd:cd05608    113 QIISGLEHLHQRRIIYRDLKPENVLLDDDGNVRISDLGLAVELKDGQ 159
PSI smart00423
domain found in Plexins, Semaphorins and Integrins;
552-594 1.81e-03

domain found in Plexins, Semaphorins and Integrins;


Pssm-ID: 214655 [Multi-domain]  Cd Length: 47  Bit Score: 37.52  E-value: 1.81e-03
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 2678964124   552 GCGHFLTCWRCLRAQRFmGCGWC--GDRCGRQKECPGS---WQQDYCP 594
Cdd:smart00423    1 RCSKYTSCSECLLARDP-YCAWCssQGRCTSGERCDSRrqnWLSGGCP 47
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
1240-1276 2.54e-03

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: 41.24  E-value: 2.54e-03
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2678964124 1240 GMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd14043    109 GMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNE 145
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
1236-1276 2.55e-03

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: 41.43  E-value: 2.55e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2678964124 1236 QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd05579    101 EIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSK 141
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
1240-1315 3.33e-03

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: 41.25  E-value: 3.33e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1240 GMEYLAEQKFVHRDLAARNCMLDESFTVKVADFG--------LARGILDKEYYsvrqhrharlpvkwMALESLQTYRFTT 1311
Cdd:cd06621    117 GLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGvsgelvnsLAGTFTGTSYY--------------MAPERIQGGPYSI 182

                   ....
gi 2678964124 1312 KSDV 1315
Cdd:cd06621    183 TSDV 186
Sema cd09295
The Sema domain, a protein interacting module, of semaphorins and plexins; Both semaphorins ...
171-395 3.38e-03

The Sema domain, a protein interacting module, of semaphorins and plexins; Both semaphorins and plexins have a Sema domain on their N-termini. Plexins function as receptors for the semaphorins. Evolutionarily, plexins may be the ancestor of semaphorins. Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems, and cancer. Semaphorins can be divided into 7 classes. Vertebrates have members in classes 3-7, whereas classes 1 and 2 are known only in invertebrates. Class 2 and 3 semaphorins are secreted; classes 1 and 4 through 6 are transmembrane proteins; and class 7 is membrane associated via glycosylphosphatidylinositol (GPI) linkage. Plexins are a large family of transmembrane proteins, which are divided into four types (A-D) according to sequence similarity. In vertebrates, type A plexins serve as co-receptors for neuropilins to mediate the signalling of class 3 semaphorins. Plexins serve as direct receptors for several other members of the semaphorin family: class 6 semaphorins signal through type A plexins and class 4 semaphorins through type B plexins. This family also includes the MET and RON receptor tyrosine kinases. The Sema domain is located at the N-terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves to recognize and bind receptors.


Pssm-ID: 200495 [Multi-domain]  Cd Length: 392  Bit Score: 41.42  E-value: 3.38e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  171 KPEACTDCVASHLGTRVTVVEQGHASYFYVASSlDPELAASFSPRSVSIRRLKSDTSGFQPgfpslsvlpkylasyliKY 250
Cdd:cd09295    111 RPRCPIDNKHSNMGVNVDSKLYSATDHDFKDGD-RPALSRRSSNVHYLRIVVDSSTGLDEI-----------------TF 172
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  251 VHSFHSG---DFVYFLTVQP------MDVRSPPsalqtRLVRLNAIEPEIGDYRELVLDCHFapKRRRRSGAPKSLQAYQ 321
Cdd:cd09295    173 VYAFVSGdddDEVYFFFRQEpveylkKGMVYVP-----RIARVCKLDVGGCHRLKKKLTSFL--KADLNCSRPQSGFAFN 245
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  322 VLQAAhsapVDAKLALDlsisegQEVLFGVFVAVKDSSsgPNSVVCAFPINHLDNLIEEGVE------RCCHPSNSSLLT 395
Cdd:cd09295    246 LLQDA----TGDTKNLI------QDVKFAIFSSCLNKS--VESAVCAYLFTDINNVFDDPVEainnrpLYAHQNQRSRLT 313
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
1233-1275 3.76e-03

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: 40.83  E-value: 3.76e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2678964124 1233 FGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLA 1275
Cdd:cd14078    106 FFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLC 148
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
1226-1276 3.79e-03

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: 40.76  E-value: 3.79e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2678964124 1226 TVKDLISFGLQVACGMEYLAEQKFVHRDLAARN--CMLDESFTVKVADFGLAR 1276
Cdd:cd14191     98 TERECIKYMRQISEGVEYIHKQGIVHLDLKPENimCVNKTGTKIKLIDFGLAR 150
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
1236-1282 3.95e-03

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: 41.02  E-value: 3.95e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2678964124 1236 QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDKE 1282
Cdd:cd05610    112 EVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVTLNRE 158
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
1237-1278 4.42e-03

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: 40.67  E-value: 4.42e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2678964124 1237 VAC---GMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGI 1278
Cdd:cd05572     99 TACvvlAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKL 143
STKc_TTBK cd14017
Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the ...
1234-1301 4.42e-03

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: 40.70  E-value: 4.42e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2678964124 1234 GLQVACGMEYLAEQKFVHRDLAARNCML----DESFTVKVADFGLARGILDKEYYSVRQHRHA---RLPVKWMAL 1301
Cdd:cd14017    103 GIQILKAIEDIHEVGFLHRDVKPSNFAIgrgpSDERTVYILDFGLARQYTNKDGEVERPPRNAagfRGTVRYASV 177
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
1229-1276 4.90e-03

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: 40.19  E-value: 4.90e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2678964124 1229 DLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLAR 1276
Cdd:cd14111    100 DVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQ 147
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
1236-1281 5.08e-03

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: 40.54  E-value: 5.08e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2678964124 1236 QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGILDK 1281
Cdd:cd05611    105 EVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLEK 150
STKc_LATS1 cd05625
Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the ...
1236-1289 5.21e-03

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270775 [Multi-domain]  Cd Length: 382  Bit Score: 40.80  E-value: 5.21e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2678964124 1236 QVACGMEYLAEQKFVHRDLAARNCMLDESFTVKVADFGLARGIL---DKEYYSVRQH 1289
Cdd:cd05625    109 ELTCAVESVHKMGFIHRDIKPDNILIDRDGHIKLTDFGLCTGFRwthDSKYYQSGDH 165
IPT cd00102
Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as ...
796-888 5.31e-03

Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor receptors), as well as, cyclodextrin glycosyltransferase and similar enzymes. Although they are involved in DNA binding in transcription factors, their function in other proteins is unknown. In these transcription factors, IPTs form homo- or heterodimers with the exception of the nuclear factor of activated Tcells (NFAT) transcription factors which are mainly monomers.


Pssm-ID: 238050 [Multi-domain]  Cd Length: 89  Bit Score: 37.44  E-value: 5.31e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124  796 PIVLDISPKCG--YSGSHVMVHGQHLTSAWHLTVSFNDGQSIVESRCagqfleQQHQ--CRLPEYmvrNPQGWATGNLSL 871
Cdd:cd00102      1 PVITSISPSSGpvSGGTEVTITGSNFGSGSNLRVTFGGGVPCSVLSV------SSTAivCTTPPY---ANPGPGPVEVTV 71
                           90
                   ....*....|....*...
gi 2678964124  872 -WGDGAAGFTLPGFRFLP 888
Cdd:cd00102     72 dRGNGGITSSPLTFTYVP 89
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
1139-1315 7.08e-03

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: 39.65  E-value: 7.08e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1139 EVQEVEAFLrEGLImrGLHHPNILALIGIMLPPEGLP-----RVLLPYmrhgdllrfirSPqrvsaqcpgwGVSASTHLC 1213
Cdd:cd14012     41 QIQLLEKEL-ESLK--KLRHPNLVSYLAFSIERRGRSdgwkvYLLTEY-----------AP----------GGSLSELLD 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2678964124 1214 RCSPVSscpqnptVKDLISFGLQVACGMEYLAEQKFVHRDLAARNCMLDESF---TVKVADFGLARGILDKeyySVRQHR 1290
Cdd:cd14012     97 SVGSVP-------LDTARRWTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDAgtgIVKLTDYSLGKTLLDM---CSRGSL 166
                          170       180
                   ....*....|....*....|....*.
gi 2678964124 1291 HARLPVKWMALESLQTY-RFTTKSDV 1315
Cdd:cd14012    167 DEFKQTYWLPPELAQGSkSPTRKTDV 192
 
Blast search parameters
Data Source: Live blast search RID = KGADF8C1016
User Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01   Maximum number of hits: 500

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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