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cd06626: STKc_MEKK4 (this model, PSSM-Id:132957 is obsolete and has been replaced by 270796)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:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #####   #            # #                                #               #
gi 6685621   1341 KWQRGNKIGEGQYGKVYTCISvdtGELMAMKEIRFQpnd--hktIKETADELKIFEGIkHPNLVRYFGVELHReeMYIFM 1418
gi 1711541   1265 RWQKRNFIGGGTFGRVYSAVDldnGEILAVKEINIQdsksmqkiFPLIKEEMSVLEILnHPNIVSYYGVEVHRdkVNIFM 1344
gi 50256138  1161 RWQQGAYIGGGASGSVYLGYSlqdNTVFAVKILPTVdlqsspalYESIKRESDVMSLLsHPNVVGFLGLEVHRnrVCLFQ 1240
gi 15214332  1119 RWQQGGLIGSGSFGTVYRAVNldtGDLMAVKEVALHkprisrpmIKRIKGEMLVLELFdHPNVVSYYGIEVHRekVNIFM 1198
gi 60688294    52 KWQRGNKIGEGQYGKVYTCINvdtGELMAMKEIRFQpnd--hktIKETADELKIFEGIkHPNLVRYFGVELHReeMYIFM 129
gi 15186734  1281 RWHRGIKIGQGRFGKVYTAVNnntGELMAMKEIAIQpge--traLKNVAEELKILEGIkHKNLVRYYGIEVHReeLLIFM 1358
gi 2088765   1124 QWALLDHIASGSFGSVHRAMDidsHRVIAAKVMRIQre-----nHKAIESEINIFRQLiHENLVKYYGVQVEDsdVIIFM 1198
gi 83773992   159 RWQQGQFIGGGTFGSVYAAINldsNYLMAVKEIRLQdpqlipkiAQQIRDEMGVLEVLdHPNIVSYHGIEVHRdkVYIFM 238
gi 159103487 1026 RWQQGRFIGGGTFGTVYLAVNldtGGLMAVKEIRFQeltsspnlFKQIHDEMNVMEMLrHPNIVEYYGIEVHRekVYIFE 1105
gi 196006109   44 RWQRSKKIGEGRFGKVYTCISldtGEIMAMKEIRFQrgd--lasIREIADEIGNIENInHPNLVKCYGAEIHReqLLIFM 121
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         ### ###  #                                   # #### #          ### #            
gi 6685621   1419 EYCdEGTLEEVSRlg--lQEHVIRLYSKQITIAINVLHeHGIVHRDIKGANIFLTs-sGLIKLGDFGCSVKLKNNAQTMP 1495
gi 1711541   1345 EYCeGGSLAALLEhgrieDEMVTQVYTLQLLEGLAYLHeSGIVHRDVKPENILLDf-nGVIKYVDFGAAKKIANNGTRLA 1423
gi 50256138  1241 EYCeGGSLAGMLEygkidDEEVVGAFTIQLLRGLEYLHtNRIEHRDLKPENILIGa-nSVLKLADFGTAKIIKSNKTLAR 1319
gi 15214332  1199 ELCqGSSLFEFLRygrieDELVIQVYVLQLLEGLAYIHsCGVSHQDVKPENILFDh-nGIMKFTDFGSAKMSGSASTKIF 1277
gi 60688294   130 EYCdEGTLEEVSRlg--lQEHVIRLYSKQITTAINVLHeHGIVHRDIKGANIFLTs-sGLIKLGDFGCSVKLKNNAQTMP 206
gi 15186734  1359 ELCsEGTLESLVEltgnlPEALTRRFTAQLLSGVSELHkHGIVHRDIKTANIFLVdgsNSLKLGDFGSAVKIQAHTTVPG 1438
gi 2088765   1199 EYCsQGTLERICHgk--mDLKMVRQYTNSLLRAVQYLHsHKIIHRDIKPANIFLDk-cTVLKLGDFGCSSRLVESSTVYG 1275
gi 83773992   239 EYCsGGSLASLLEhgrveDETVIMVYALQLLEGLAYLHqAGIVHRDIKPENILLDh-nGIIKYVDFGAAKIIARQGRTVV 317
gi 159103487 1106 EYCqGGSLAQLLEhgrieDEIVLQVYALQMLDGLMYLHsQGVVHRDIKPDNILLDh-mGVIKFVDFGAAKVLSRRSLSMH 1184
gi 196006109  122 EYCnEGTISDAAKng--lPEAMIRRYTKQILVAIDFLHeNGIVHRDIKGNNIFLAr-nGLIKLGDFGCSVKLSKTTTMYG 198
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                          #### #                                    #    
gi 6685621   1496 Ge----------------------------VNSTLGTAAYMAPEVITRak-------geGHGRAADIWSLGCVVIEMVTG 1540
gi 1711541   1424 SmnkienadgehedvthvsdskavknnenaLLDMMGTPMYMAPESITGst-------tkGKLGADDVWSLGCVVLEMITG 1496
gi 50256138  1320 Trgga----------------------hakMEGLEGTPMYMAPEMIKNqr--------tGKLGACDIWGLGCIVLQMITG 1369
gi 15214332  1278 Eqltqqeeeefek-----dseflqhldqnrGYSLTGTPTYMAPELILGnp--------sERVGAMDIWSLGCVIVEMATG 1344
gi 60688294   207 Ge----------------------------VNSTLGTAAYMAPEVITRak-------geGHGRAADIWSLGCVLIEMVTG 251
gi 15186734  1439 E-----------------------------LQGYVGTQAYMAPEVFTKtn-------sdGHGRAADIWSVGCVVVEMASG 1482
gi 2088765   1276 E-----------------------------FQTTAGTPQFMAPEIYSYgekdettgsysGYGRSVDIWALGATVVNMMTG 1326
gi 83773992   318 Pmdafasaghkeaiv--pkdaqianqrgknQKTMTGTPMYMSPEVIRGdsn-----kliHRQGAVDIWSLGCVILEMATG 390
gi 159103487 1185 Tggrapvhl--------------pgavdarGQSLQGTPMYMAPEVVRGet--------hGREGAADIWSLGCVVLECAKG 1242
gi 196006109  199 E-----------------------------FNNMRGTTAFMAPEMITEnk-------rkGHGRAVDIWSLGCVVIEMVTG 242
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
Feature 1             #                                                            
gi 6685621   1541 KRPWHeye--hnFQIMYKVGm-GHKPPIPERl--SPEGKDFLSHCLESdPKMRWTASQLLDHSFV 1600
gi 1711541   1497 RRPWAnld--neWAIMYHVAa-GHTPQFPTKdevSSAGMKFLERCLIQnPSKRASAVELLMDPWI 1558
gi 50256138  1370 RKPWSfldfdneWAIMFHLGatKEPPPLPDPnemSDQGIEFIDQCLSLdPEARPVASELLQDEWL 1434
gi 15214332  1345 SPPWPrld--nhFSLMYHIAa-HNPPIIPADdqlSPLGQNFLKRCFVSdPNQRATAAELLMDPWV 1406
gi 60688294   252 KRPWHeye--hnFQIMYRVGm-GHKPPIPEKl--STEGKDFLAHCLESePKRRWTASALLDHPFV 311
gi 15186734  1483 KRPWAqfd--snFQIMFKVGm-GEKPQAPESl--SQEGHDFIDHCLQHdPKRRLTAVELLEHNFC 1542
gi 2088765   1327 KVPFEgq---trHQIAFALCfrKQKPTYPDIadkRPDVKRFFDNCFEFlPNDRPTAAELLQTTFA 1388
gi 83773992   391 RRPWSald--neWAIMYNIAq-GNQPQLPTHdqlSDMGIDFLRRCFECdPLKRPTAAELLQHEWI 452
gi 159103487 1243 TRPWSqld--neWAIMFHIGmaQQCPALPDEtqlSALGIDFIKQCLTIdPFKRPTAVELRQHAWI 1305
gi 196006109  243 RHPWSefd--deFAIMFQVGs-GAAPVTPDSi--SDEGKDFLSRCLVHdPQDRWTTSELLNHPFV 302

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