Conserved Protein Domain Family
STKc_MEKK4

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cd06626: STKc_MEKK4 (this model, PSSM-Id:132957 is obsolete and has been replaced by 270796)
Catalytic domain of the Protein Serine/Threonine Kinase, MAP/ERK kinase kinase 4
Serine/threonine kinases (STKs), MAP/ERK kinase kinase 4 (MEKK4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MEKK4 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that 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. MEKK4 activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses.
Statistics
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PSSM-Id: 132957
View PSSM: cd06626
Aligned: 14 rows
Threshold Bit Score: 418.665
Threshold Setting Gi: 2088765
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                #####   #            # #                                #               #
6685621      1341 KWQRGNKIGEGQYGKVYTCISvdtGELMAMKEIRFQpnd--hktIKETADELKIFEGIkHPNLVRYFGVELHReeMYIFM 1418 human
P53599       1265 RWQKRNFIGGGTFGRVYSAVDldnGEILAVKEINIQdsksmqkiFPLIKEEMSVLEILnHPNIVSYYGVEVHRdkVNIFM 1344 baker's yeast
EAL18865     1161 RWQQGAYIGGGASGSVYLGYSlqdNTVFAVKILPTVdlqsspalYESIKRESDVMSLLsHPNVVGFLGLEVHRnrVCLFQ 1240 Cryptococcus ...
O74304       1119 RWQQGGLIGSGSFGTVYRAVNldtGDLMAVKEVALHkprisrpmIKRIKGEMLVLELFdHPNVVSYYGIEVHRekVNIFM 1198 fission yeast
AAH91661       52 KWQRGNKIGEGQYGKVYTCINvdtGELMAMKEIRFQpnd--hktIKETADELKIFEGIkHPNLVRYFGVELHReeMYIFM 129  zebrafish
BAB62891     1281 RWHRGIKIGQGRFGKVYTAVNnntGELMAMKEIAIQpge--traLKNVAEELKILEGIkHKNLVRYYGIEVHReeLLIFM 1358 fruit fly
AAB57718     1124 QWALLDHIASGSFGSVHRAMDidsHRVIAAKVMRIQre-----nHKAIESEINIFRQLiHENLVKYYGVQVEDsdVIIFM 1198 nematode
BAE64117      159 RWQQGQFIGGGTFGSVYAAINldsNYLMAVKEIRLQdpqlipkiAQQIRDEMGVLEVLdHPNIVSYHGIEVHRdkVYIFM 238  Aspergillus o...
EDP42380     1026 RWQQGRFIGGGTFGTVYLAVNldtGGLMAVKEIRFQeltsspnlFKQIHDEMNVMEMLrHPNIVEYYGIEVHRekVYIFE 1105 Malassezia gl...
XP_002112921   44 RWQRSKKIGEGRFGKVYTCISldtGEIMAMKEIRFQrgd--lasIREIADEIGNIENInHPNLVKCYGAEIHReqLLIFM 121  Trichoplax ad...
Feature 1         ### ###  #                                   # #### #          ### #            
6685621      1419 EYCdEGTLEEVSRlg--lQEHVIRLYSKQITIAINVLHeHGIVHRDIKGANIFLTs-sGLIKLGDFGCSVKLKNNAQTMP 1495 human
P53599       1345 EYCeGGSLAALLEhgrieDEMVTQVYTLQLLEGLAYLHeSGIVHRDVKPENILLDf-nGVIKYVDFGAAKKIANNGTRLA 1423 baker's yeast
EAL18865     1241 EYCeGGSLAGMLEygkidDEEVVGAFTIQLLRGLEYLHtNRIEHRDLKPENILIGa-nSVLKLADFGTAKIIKSNKTLAR 1319 Cryptococcus ...
O74304       1199 ELCqGSSLFEFLRygrieDELVIQVYVLQLLEGLAYIHsCGVSHQDVKPENILFDh-nGIMKFTDFGSAKMSGSASTKIF 1277 fission yeast
AAH91661      130 EYCdEGTLEEVSRlg--lQEHVIRLYSKQITTAINVLHeHGIVHRDIKGANIFLTs-sGLIKLGDFGCSVKLKNNAQTMP 206  zebrafish
BAB62891     1359 ELCsEGTLESLVEltgnlPEALTRRFTAQLLSGVSELHkHGIVHRDIKTANIFLVdgsNSLKLGDFGSAVKIQAHTTVPG 1438 fruit fly
AAB57718     1199 EYCsQGTLERICHgk--mDLKMVRQYTNSLLRAVQYLHsHKIIHRDIKPANIFLDk-cTVLKLGDFGCSSRLVESSTVYG 1275 nematode
BAE64117      239 EYCsGGSLASLLEhgrveDETVIMVYALQLLEGLAYLHqAGIVHRDIKPENILLDh-nGIIKYVDFGAAKIIARQGRTVV 317  Aspergillus o...
EDP42380     1106 EYCqGGSLAQLLEhgrieDEIVLQVYALQMLDGLMYLHsQGVVHRDIKPDNILLDh-mGVIKFVDFGAAKVLSRRSLSMH 1184 Malassezia gl...
XP_002112921  122 EYCnEGTISDAAKng--lPEAMIRRYTKQILVAIDFLHeNGIVHRDIKGNNIFLAr-nGLIKLGDFGCSVKLSKTTTMYG 198  Trichoplax ad...
Feature 1                                          #### #                                    #    
6685621      1496 Ge----------------------------VNSTLGTAAYMAPEVITRak-------geGHGRAADIWSLGCVVIEMVTG 1540 human
P53599       1424 SmnkienadgehedvthvsdskavknnenaLLDMMGTPMYMAPESITGst-------tkGKLGADDVWSLGCVVLEMITG 1496 baker's yeast
EAL18865     1320 Trgga----------------------hakMEGLEGTPMYMAPEMIKNqr--------tGKLGACDIWGLGCIVLQMITG 1369 Cryptococcus ...
O74304       1278 Eqltqqeeeefek-----dseflqhldqnrGYSLTGTPTYMAPELILGnp--------sERVGAMDIWSLGCVIVEMATG 1344 fission yeast
AAH91661      207 Ge----------------------------VNSTLGTAAYMAPEVITRak-------geGHGRAADIWSLGCVLIEMVTG 251  zebrafish
BAB62891     1439 E-----------------------------LQGYVGTQAYMAPEVFTKtn-------sdGHGRAADIWSVGCVVVEMASG 1482 fruit fly
AAB57718     1276 E-----------------------------FQTTAGTPQFMAPEIYSYgekdettgsysGYGRSVDIWALGATVVNMMTG 1326 nematode
BAE64117      318 Pmdafasaghkeaiv--pkdaqianqrgknQKTMTGTPMYMSPEVIRGdsn-----kliHRQGAVDIWSLGCVILEMATG 390  Aspergillus o...
EDP42380     1185 Tggrapvhl--------------pgavdarGQSLQGTPMYMAPEVVRGet--------hGREGAADIWSLGCVVLECAKG 1242 Malassezia gl...
XP_002112921  199 E-----------------------------FNNMRGTTAFMAPEMITEnk-------rkGHGRAVDIWSLGCVVIEMVTG 242  Trichoplax ad...
Feature 1             #                                                            
6685621      1541 KRPWHeye--hnFQIMYKVGm-GHKPPIPERl--SPEGKDFLSHCLESdPKMRWTASQLLDHSFV 1600 human
P53599       1497 RRPWAnld--neWAIMYHVAa-GHTPQFPTKdevSSAGMKFLERCLIQnPSKRASAVELLMDPWI 1558 baker's yeast
EAL18865     1370 RKPWSfldfdneWAIMFHLGatKEPPPLPDPnemSDQGIEFIDQCLSLdPEARPVASELLQDEWL 1434 Cryptococcus neoformans var....
O74304       1345 SPPWPrld--nhFSLMYHIAa-HNPPIIPADdqlSPLGQNFLKRCFVSdPNQRATAAELLMDPWV 1406 fission yeast
AAH91661      252 KRPWHeye--hnFQIMYRVGm-GHKPPIPEKl--STEGKDFLAHCLESePKRRWTASALLDHPFV 311  zebrafish
BAB62891     1483 KRPWAqfd--snFQIMFKVGm-GEKPQAPESl--SQEGHDFIDHCLQHdPKRRLTAVELLEHNFC 1542 fruit fly
AAB57718     1327 KVPFEgq---trHQIAFALCfrKQKPTYPDIadkRPDVKRFFDNCFEFlPNDRPTAAELLQTTFA 1388 nematode
BAE64117      391 RRPWSald--neWAIMYNIAq-GNQPQLPTHdqlSDMGIDFLRRCFECdPLKRPTAAELLQHEWI 452  Aspergillus oryzae
EDP42380     1243 TRPWSqld--neWAIMFHIGmaQQCPALPDEtqlSALGIDFIKQCLTIdPFKRPTAVELRQHAWI 1305 Malassezia globosa CBS 7966
XP_002112921  243 RHPWSefd--deFAIMFQVGs-GAAPVTPDSi--SDEGKDFLSRCLVHdPQDRWTTSELLNHPFV 302  Trichoplax adhaerens

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