2DYL


Conserved Protein Domain Family
PKc_MKK7

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cd06618: PKc_MKK7 (this model, PSSM-Id:132949 is obsolete and has been replaced by 270791)
Click on image for an interactive view with Cn3D
Catalytic domain of the dual-specificity Protein Kinase, MAP kinase kinase 7
Protein kinases (PKs), MAP kinase kinase 7 (MKK7) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 (not included in this subfamily) and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade.
Statistics
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PSSM-Id: 132949
View PSSM: cd06618
Aligned: 10 rows
Threshold Bit Score: 482.258
Threshold Setting Gi: 16950399
Created: 4-Apr-2007
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 33 residues -Click on image for an interactive view with Cn3D
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                               ##### # #            # #                              #   
2DYL_A         11 GYLTIGGQRYQaeiNDLENLGEMGSGTCGQVWKMRFrktgHVIAVKQMRRSgnkEENKRILMDLDVVLKShdCPYIVQCF 90
gi 73620965   181 GKLNINGRQYPtdiNDLKHLGDLGNGTSGNVVKMMHlssnTIIAVKQMRRTgnaEENKRILMDLDVVLKShdCKYIVKCL 260
gi 68355102   105 GYLKIDGQRYPaevTDLISEGEIGSGTCGQVFKVRFkktgHVIAVKQMRRTgnkDENKRILMDLDVVLKShdCPYIIQCY 184
gi 46329501   101 GYLGIDGQKYPadiNDLENLGEIGSGTCGQVWKMRFkktgHVIAVKQMRRSgnkEENKRILMDLDVVLKShdCPYIVQCY 180
gi 70570165   114 GKLRIDSMIYEakvEQFENLGQIGSGTCGQVYKMRYit-gHVMAVKQMHRSgnrEENKRILMDLDIVQKShdCPNIVKCY 192
gi 21106013    56 GYLTLQGNRRKadlKELQFVEDIGHGSCGTVTKCRYk--sVIMAVKTMPRTsnsYEMSRILMDLDVICLSfdCPYIVRCF 133
gi 16950399   106 GTLEIDGEKQVvdpNEIHIISLLGSGSCGVVESATVr--sKLMAVKTMYKNdnkENLKRILRDVRIMSMCn-SPFIVTSY 182
gi 156390779   27 GILKLGDKKYDfslDDLEMSGEIGYGTCGQVCKMKHkksgQVLAVKRMARShnkEEQKRILMDLEVVMKShdCPYIVTCM 106
gi 158595559  126 GRITIMKTMYEttkESLKRIGELGSGTCGVVYKARFeqtgTIMAVKQMVMTsvaEENKRVLMDLEVVLXShdCPHIVRCY 205
gi 196000032   13 GLLTIDGKKYKiglDDLQVMGQIGSGTCGTVYAMEHaatrSVIAVKKIPRIqneEEKKRVLMDLQVVMKShdCPYIVKCF 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     #### ## ##                                         # #### #         
2DYL_A         91 GTFITntDVFIAMELMgTCAEKLKKRmqg----piPERILGKMTVAIVKALYYLKEkHGVIHRDVKPSNILLDerGQIKL 166
gi 73620965   261 GCFVRdpDVWICMELMsMCFDKLLKLskk----pvPEQILGKVTVATVNALSYLKDkHGVIHRDVKPSNILIDerGNIKL 336
gi 68355102   185 GAIVTntDVFIAMELMgTCAEKLKKRiqg----piPEAILGKMTVAIVNALLYLKEkHGVIHRDVKPSNILLDakGQIKL 260
gi 46329501   181 GTFITntDVFIAMELMgTCAEKLKKRiqg----piPEAILGKMTVAIVNALYYLKEkHGVIHRDVKPSNILLDasGQIKL 256
gi 70570165   193 GTFVTevNVWICMELMeTCFDKLKKKing----pmPENILGKLTVSVVKALHYLKEkHGVIHRDVKPSNILVNklGDVKL 268
gi 21106013   134 GYFITnfDVRVCMECMaTCLDRLLIRikq----piPERIIGKLSVSIIKALHYLKTkHQIMHRDVKPSNILLDwsGVIKL 209
gi 16950399   183 GYFMFdsSVKICMQIMsACCEKLLRRiyhskldffPEFVAGHIVYSAISALDYLKEkHSIIHRDIKPSNILFDdsGNVKL 262
gi 156390779  107 GALISksDVFICMELMaTCLDKLLKRlqn----piPEHILGKMAVAIVKALHYLKEeHGVMHRDVKPSNMLLDsaGCVKL 182
gi 158595559  206 GCFITdfEVLICMELMaTCLDKLSKRvqg----gfPEDILGKMAVSIIKALDYLKVtQNIIHRDVKPSNILLDlnGTVKL 281
gi 196000032   93 GLLIAesDILICMEKMsTCLCKLLTRtgq----piPEDILGKITVAVVKALHYLKQnHGVIHRDVKPSNILLDadGNVKL 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          #  #            #### #                               #        #                
2DYL_A        167 CDFGISGRLVDDKAKDRSAGCAAYMAPERIDPpdptkpDYDIRADVWSLGISLVELAtGQFPYKncktDFEVLTKVLQEE 246
gi 73620965   337 CDFGISGRLVDSKANTRSAGCAAYMAPERIDPkk---pKYDIRADVWSLGITLVELAtARSPYEgcntDFEVLTKVLDSE 413
gi 68355102   261 CDFGISGRLVDSKAKTRSAGCAAYMAPERIDPpdpskpDYDIRADVWSLGISLVELAtGQFPYKncktDFEVLTKVLQED 340
gi 46329501   257 CDFGISGRLVDSKAKTRSAGCAAYMAPERIDPpdptkpDYDIRADVWSLGISLVELAtGQFPYKncktDFEVLTKVLQEE 336
gi 70570165   269 CDFGISGRLVDSQAKTRAAGCTAYMAPERISPdps-hpNYDIRADVWSLGISLVELAtGVFPYHncktDFEMLTKILEEA 347
gi 21106013   210 CDFGIAGRLIESRAHSKQAGCPLYMGPERLDPnn--fdSYDIRSDVWSFGVTLVELAtGQYPYAg--tEFDMMSKILNDE 285
gi 16950399   263 CDFGISGFMTDSMAHSKSAGCPPYMAPERLTIet--nsKYDVRSDVWSLGITVYQLVtGLYPFPlndmEFTTLTIIANLN 340
gi 156390779  183 CDFSISGRLVDSKAKTKSAGCAAYMAPERIDPpdpmnpNYDVRADVWSLGISLVELAtGEFPYRncttEFEVLTRVMGED 262
gi 158595559  282 CDFGIAGRLVDSMARTRTAGCSAYMSPERLEAq----dEYDVRADVWSIGISLVELAkGEYPYRgcnsEFEVLSRIVSDP 357
gi 196000032  169 CDFGISGRLVDSKARTRGKGCAAYMSPERIDPsnp-tgTYDIRADVWSLGISLVELAtGKFPYDecegEFQVLTRILQDD 247
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
Feature 1                                                                                       
2DYL_A        247 PPLLPGHm----gFSGDFQSFVKDCLTKDHRKRPKYNKLLEHSFIKRYETle-------------vDVASWFKDVMAK 307
gi 73620965   414 PPCLPYGeg--ynFSQQFRDFVIKCLTKNHQDRPKYPELLAQPFIRIYESak-------------vDVPNWFQSIKDN 476
gi 68355102   341 PPVLPLSm----gFSPDFQSFVKDCLTKDHRKRPKYHKLLEHSFIRRYEVse-------------vDVAGWFQAVMER 401
gi 46329501   337 PPVLPHNm----gFTLLFQSFVKDCLTKDHRKRPKYNKLMEHPFLRRYETse-------------vEVASWFQDIMAR 397
gi 70570165   348 PPELPNDq----nFSIGFKRFVSFCCTKDYRYRPKYRDLLEHEFVRRHEHsm-------------vDIPAWLRKVLIT 408
gi 21106013   286 PPRLDPAk-----FSPDFCQLVESCLQRDPTMRPNYDMLLQHPFVVHHEKie-------------tDVEEWFADVMGE 345
gi 16950399   341 LPSPSLReetkrsFSPLFIEFLDLCLRKDVRERPEYRQLMKHDFYLDYDPasgsaykfkaingkcnQVADWFVDVIRL 418
gi 156390779  263 PPSLPGSk----gFSHDFSSFVDECLTKDFHYRPKYNKLLVHPFITSYDSke-------------vDVAGWLKESLAS 323
gi 158595559  358 APVLNPEe----gFSPMFCDFLRLCLTKNYQFRPKYKELLQHEWVIHYETar-------------vDVAGWYQRIVQS 418
gi 196000032  248 PPKLPSNg----qFSQEFCSFVEKCLIKDHDRRPKYAELLQHKFIQIYETkd-------------vDVASWFNQLIEE 308

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