Conserved Protein Domain Family
STKc_MAP4K3_like

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cd06613: STKc_MAP4K3_like (this model, PSSM-Id:173727 is obsolete and has been replaced by 270788)
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase-like Protein Serine/Threonine Kinases
Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 3 (MAPKKKK3 or MAP4K3)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K3-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. 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, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. 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).
Statistics
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PSSM-Id: 173727
Aligned: 19 rows
Threshold Bit Score: 464.075
Created: 21-Aug-2006
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
Feature 1:active site [active site]
Evidence:
  • Comment:The active site is composed of the ATP binding site and the substrate binding site. The substrate binding site is based on the binding of human PAK4 to a consensus peptide.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                  #####   #            # #                              #               
Q8IVH8        12 PQEDFELIQRIGSGTYGDVYKARNVNtGELAAIKVIKLEPge--dfAVVQQEIIMMKDCKHPNIVAYFGSYLRrDKLWIC 89  human
XP_643908     25 PQTIYHIQERLGKGSFGQVFKAVHFAnGKVVAIKIISLDDqe--aiKDVRKEISILAECNYPNIVQYFGSYFKdHQLWIV 102 Dictyostelium d...
2352084      245 PTTKYEFLNELGKGSYGSVYKARDLKtSEIVAVKVISLTEgee-gyEEIRGEIEMLQQCNHPNVVRYLGSYQGeDYLWIV 323 thale cress
AAX28389      10 PKEEYKILSPIGSGTYGDVFKAVHRErRTLVAVKVMKIDLkd--diRSICQEIHTLRECRHPNIVQFYGSYLRnNKLWIC 87  Schistosoma jap...
AAX69858      16 PEELYEELGPIGVGNYGSVIKARNRHtQEITAIKLVLLVDkd--erDFVQREISILKHCRHPNIVHYYGAHKSlSKLWIV 93  Trypanosoma brucei
XP_001641110  14 PDKVFDLIEKVGGGTYGDVFKARVIAtGDLAAVKVVKVEPgd--dfELIQQEIAMMQQCRHNNIINYIGAYMRrDKLWIG 91  starlet sea ane...
XP_001758138 135 PSLKYELLNELGKGSYGAVYKARDLLtSELVAVKVISLTEgee-gyEEIRGEIGMLQQCNHPNVVRYLGSFQGeDYLWIV 213 Physcomitrella ...
XP_002108638   8 LQEQFDIKKKIGSGSYGDVFKVRVRQtDQIAALKVIKIQEdd--dlAIIEQEIQILRGCVHPNIVQYFHSEFRrQQLWIT 85  Trichoplax adha...
XP_001743065  11 PESVFELIKQIGSGSYGSVHKARIIKsGKSAAVKMINMEDgd--elEDVQNEIRMLESCKHDNIVAYFGAFQRgHTMWIA 88  Monosiga brevic...
XP_001700998   6 ARSRFQLQSVLGKGAYGTVYAAIDTAsGERVAIKVIPVTEqdreefKQIQREVAFLADCNHPNVVRYLGSYRLsGELWIV 85  Chlamydomonas r...
Feature 1        ####  ##  #                                    # #### #          #  #           
Q8IVH8        90 MEFCGGGSLQDIYHVt-gPLSELQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTdnGHVKLADFGVSAQITATIaKR 168 human
XP_643908    103 MEYCGGGSVSDLLQVi-dTISEDEIALICREALKGLNYLHEFKKIHRDIKGGNILLNdrGEVKLADFGVSAQLFNTFsKR 181 Dictyostelium d...
2352084      324 MEYCGGGSVADLMNVteeALEEYQIAYICREALKGLAYLHSIYKVHRDIKGGNILLTeqGEVKLGDFGVAAQLTRTMsKR 403 thale cress
AAX28389      88 MEYCGGQSMQDIYLYtrrPLEEDCIAFVSRETLQGLNFMHNRGRIHRDIKGANILLTddGHVKVADFGVAAQLSTSIaKR 167 Schistosoma jap...
AAX69858      94 MEYCEGGSIDMVYKVlrhPLPEPLIAYVCRQVLLGLQYLHANRKIHRDIKGGNILLTrdGGVKLADFGVSTELSHSLsRR 173 Trypanosoma brucei
XP_001641110  92 MEYCGGGSIQDVYCVt-gPCSETQISFVTVETLKGLAYLHEKSLMHRDIKGANILLTtnGEVKLADFGISARITETMkKR 170 starlet sea ane...
XP_001758138 214 MEYCGGGSVADLMNItdeALEEQQIAYICREALKGLTYLHSIFKVHRDIKGGNILLTeqGEVKLGDFGVAAQLTRTMsKR 293 Physcomitrella ...
XP_002108638  86 MEYCGGGSLQDIYKRt-gALTEQQIAFVCRESLRGLDYLHQQQKLHRDIKGANILLTedGDIKLADFGVAAQITNTFqKR 164 Trichoplax adha...
XP_001743065  89 MEYCGGGSVSDIYNKnctPLEEDVIAHITFYSLLGLEYLHQSHLVHRDIKGGNILLTedGCVKLADLGVSAQLTSTLaKR 168 Monosiga brevic...
XP_001700998  86 MEYCGGGSVSDLLSAgraPLPEELIAHICCESLKGLAYLHGLGKVHRDIKCGNILLTssGDVKIADFGVSAQLTNTMsKR 165 Chlamydomonas r...
Feature 1          #### #                                #        #                              
Q8IVH8       169 KSFIGTPYWMAPEVAAVerk---ggYNQLCDLWAVGITAIELAELQPPMFDLHPMRALFLMTKsnfQPPKLKDKMKWSNS 245 human
XP_643908    182 NTFVGTPYWMAPEVIQEn------kYDGKADVWSLGITAIEMAEGLPPNSNVHPMRVIFMIPRe--ESPALTDKSIWSDK 253 Dictyostelium d...
2352084      404 NTFIGTPHWMAPEVIQEn------rYDGKVDVWALGVSAIEMAEGLPPRSSVHPMRVLFMISIe--PAPMLEDKEKWSLV 475 thale cress
AAX28389     168 TTLIGTPYWMAPEVASIecr--gsgYDGKCDIWGVGITAIEYAELQPPMFDLDPRKALQILGSrnyKPPSLQDRHKWSPL 245 Schistosoma jap...
AAX69858     174 NTFVGTLLWMAPEAILEl------dYDEKADLWSLGITLIEMAEGAPPYIDTHPARALFMIPKm--DPPSLQDKERWSPQ 245 Trypanosoma brucei
XP_001641110 171 KSFIGTPYWMAPEMAAVert---ggYDLKCDIWAVGITAIEMAELQPPMFDLHPMRALYIIGKksfIPPTLKEKDKWSNE 247 starlet sea ane...
XP_001758138 294 NTFIGTPHWMAPEVIQEn------rYDGKVDVWALGVSAIEMAEGLPPRSNVHPMRVLFMISRe--PAPMLEDKERWSLV 365 Physcomitrella ...
XP_002108638 165 QTFIGTPYWMAPEVANVere---ggYDQACDIWAVGITAIELAQLKPPLYEIHPMKALLIIGKsdyKPPKLKEKNLWTVK 241 Trichoplax adha...
XP_001743065 169 KSFIGTPYWIAPEIIAVemkmgpdgYTSRCDVWSMGITCIEMAEMQPPMFDLHPMRALYLIPKn--PPPKLTDKSRWSKD 246 Monosiga brevic...
XP_001700998 166 QTFIGTPHWMAPEVIQEs------rYDGKVDVWALGISAIEMAEMTPPRWNVHPLRVIFMISRd--PPPRLSQPEKWSPV 237 Chlamydomonas r...
Feature 1                                   
Q8IVH8       246 FHHFVKMALTKnPKKRPTAEKLLQHPF 272 human
XP_643908    254 FQDFISKCLTKdPAERPTAKELLNHEF 280 Dictyostelium discoideum AX4
2352084      476 FHDFVAKCLTKePRLRPTAAEMLKHKF 502 thale cress
AAX28389     246 FHSFVKCCLIKaERRRPDAATMLTHNF 272 Schistosoma japonicum
AAX69858     246 MTLFLKRLLTKdHNARPTATTMLNDPF 272 Trypanosoma brucei
XP_001641110 248 MHHFIKVALIKnPKKRPSADKMLTHPF 274 starlet sea anemone
XP_001758138 366 FHDYVAKCLTKePRLRPTASALLSHKF 392 Physcomitrella patens subsp. patens
XP_002108638 242 FHDFIKETLTKdYTRRPSAGKLLQHHF 268 Trichoplax adhaerens
XP_001743065 247 FREFIKATLVKnPQKRPSAGALTKVRD 273 Monosiga brevicollis MX1
XP_001700998 238 FIDTMTQALIKdPKQRPAARYLLQHRF 264 Chlamydomonas reinhardtii

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