3FME,3ENM


Conserved Protein Domain Family
PKc_MKK3_6

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cd06617: PKc_MKK3_6 
Click on image for an interactive view with Cn3D
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 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.
Statistics
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PSSM-Id: 173729
View PSSM: cd06617
Aligned: 11 rows
Threshold Bit Score: 521.6
Threshold Setting Gi: 115720219
Created: 4-Apr-2007
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:3FME; Human MEK6 activated mutant binds staurosporine; contacts at 4A.
    View structure with Cn3D
  • Comment:Based also on human MEK1 and MEK2, and other related proteins with structure bound to ATP or inhibitors.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                ##### # #            # #                              #               ##
3FME_A         7 DDLEPIMELGRGAYGVVEKMRHVPsgQIMAVKRIRATVNsqEQKRLLMDLDISMRTVDCPFTVTFYGALFREGDVWICME 86
3ENM_A        34 DDLEPIXELGRGAYGVVEKXRHVPsgQIXAVKRIRATVNsqEQKRLLXDLDISXRTVDCPFTVTFYGALFREGDVWICXE 113
gi 34784599   52 DDLEPIEELGRGAYGVVEKMRHVPseQIMAVKRIRATVNsqEQKRLLMDLDISMRTVDCHFTVTFYGALFREGDVWICME 131
gi 47939296   55 DDLEQIGELGRGAYGVVDKMRHVPsgVIMAVKRIRATVNtqEQKRLLMDLDISMRTVDCFYTVTFYGALFREGDVWICME 134
gi 5101687    44 DSLEKICDLGRGAYGIVDKMRHKQtdTVLAVKRIPMTVNirEQHRLVMDLDISMRSSDCPYTVHFYGAMYREGDVWICME 123
gi 70570148   65 DDLTIVEELGRGAYGVVDKMKHKSteTIIAVKRIRATLNtqEQKRLLMDLDVSMRSVDCDYTVTFYGALFRQGDVWICME 144
gi 156375514  56 DDLQEIRELGHGAYGYVYEMLHVPtsTVMAVKKIRANVNstEQKRLLMDLDISMRVSDYPYTVHFYGALFREGDVWICME 135
gi 115720219  51 RDMIVIENLGRGAYGIVDKTRHEPteSIMAVKKMRAQVNstEDKRILMDMDVAMRSSDCVYTVEFYGALFQEGDVWICME 130
gi 21629476   48 TDLVVLEELGKGGYGIVEKMQHRQsgIIMAVKRIKSSINdqSQKQMLNELDACRRSDCCPQMVRFYGAMFREGDVWICME 127
gi 83318911  118 DDFQFVDTLGRGAYGVVDKMKHPPtgTIVAVKRLAYSLEsaDYKSLLMDLNVSLRTGHCPNIVHFYGALFGRGDVWIFME 197
gi 24638466   62 DDLVTISELGRGAYGVVEKVRHAQsgTIMAVKRIRATVNsqEQKRLLMDLDINMRTVDCFYTVTFYGALFREGDVWICME 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ## ## ##                                           # ## #          #            
3FME_A        87 LMDTSLDKFYKQVIdkg-qtIPEDILGKIAVSIVKALEHLHSkLSVIHRDVKPSNVLINalGQVKMCDFGISGYLVDDVA 165
3ENM_A       114 LXDTSLDKFYKQVIdkg-qtIPEDILGKIAVSIVKALEHLHSkLSVIHRDVKPSNVLINalGQVKXCDFGISGYLVDDVA 192
gi 34784599  132 LMDTSLDKFYKDVIdkg-ltIPEDILGKIAVSIVKALEHLHSkLSVIHRDVKPSNVLINkeGQVKMCDFGISGYLVDSVA 210
gi 47939296  135 LMDTSLDKFYKQVHekg-ktIPEDILGKITVSIVKALEHLHSnLSVIHRDVKPSNVLINmqGQVKMCDFGISGYLVDSVA 213
gi 5101687   124 VMSTSLDKFYPKVFlhd-lrMEESVLGKIAMSVVRALHYLHAqLKVIHRDVKPSNILINraGQVKICDFGISGYLVDSIA 202
gi 70570148  145 VMDTSLDQFYKKVKdrg-lkTGEDVLGIIAVSIVKALRYLQEtLHVIHRDVKPSNVLLNknGQVKLCDFGISGQLVDSLV 223
gi 156375514 136 LMKTSLYDLYKQVFskpdrrIPEEVLGKIAVSVVSALEYLHSnLKVIHRDVKPSNILVDerGNFKLCDFGISGQLVDSLA 215
gi 115720219 131 VMDTCLDKLYKNKLkpqkifVPENILSRISFSIVSALKYLQTrLKVIHRDVKPSNVLANhnGKIKLCDFGISGQLVNSMA 210
gi 21629476  128 VMDTSLDKFYRHAYkig-khIPEPFIGKMALSVIEGLNFMKEqLNLIHRDVKPSNILLNrhGQVKICDFGISGHLTNSMA 206
gi 83318911  198 VMDTSLDKFYKKVYqhk-mtIKEPALAKITLGVMMGLSYLKEkLSVIHRDVKPSNILANrqGNIKLCDFSVSGNLIDSLS 276
gi 24638466  142 LMDTSLDKFYRKVLdkn-mtIPEDILGEIAVSIVRALEHLHSkLSVIHRDVKPSNVLINkeGHVKMCDFGISGYLVDSVA 220
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
3FME_A       166 KDiDAGCKPYMAPERINPELnqkGYSVKSDIWSLGITMIELAilRFPYDSWgtPFQQLKQVVEEPSPQLPADk-FSAEFV 244
3ENM_A       193 KDiDAGCKPYXAPERINPELnqkGYSVKSDIWSLGITXIELAilRFPYDSWgtPFQQLKQVVEEPSPQLPADk-FSAEFV 271
gi 34784599  211 KTmDAGCKPYMAPERINPELnqkGYSVKSDIWSLGITLIELAilRFPYDSWgtPFQQLKQVVEEPSPQLPADk-FSAEFV 289
gi 47939296  214 KTmDAGCKPYMAPERINPETnqkGYNVKSDIWSLGITMIELAilRFPYDSWgtPFQQLKQVVEGPSPQLPADr-FSADFV 292
gi 5101687   203 KTiDAGCKPYMAPERIDPQGnpaQYDIRSDVWSLGIGMIEMAtgRYPYDNWrtPFEQLRQVVEDSPPRLPEGt-FSPEFE 281
gi 70570148  224 KTiDAGCKPYMAPERIDPAQnqqGYDVKSDVWSLGITMIEVAtgDFPYDTWrnPFQQLKQVVEDPSPKLPANt-FSLELD 302
gi 156375514 216 KTvDAGCKPYMAPERINPDRdmkGYDIRSDIWSLGITMIELAtgKFPYTQWktPFEQLKQVVHEPSPSLPEGp-FSLNFR 294
gi 115720219 211 KTqDAGSRQYMAPERIDPDMsakGYDVKSDVWSFGITMIEIAtnAYPYERWhdMFQQLTQVVKGTSPALPKEk-FSEDIQ 289
gi 21629476  207 KTvQAGCKPYMPPERIDGETk-sAYDVRADVWSLGITIIEIAvgTHPYANWktPFEQLKQVVKEPPPKLPMEsgFSVDCQ 285
gi 83318911  277 KT-KIGARPYMAPEKVNPDGe-qHFDVRSDIWSLGXSLIELAtgKFPYATWktPFEQIKQVVQGPSPTLPNEg-FSPQIQ 353
gi 24638466  221 KTmDAGCKPYMAPERINPELnqkGYNVKSDVWSLGITMIEMAilRFPYESWgtPFQQLKQVVEEPSPQLPADr-FSPEFV 299
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
Feature 1                                                          
3FME_A       245 DFTSQCLKKn---SKERPTY--PELMQHPFFTLHESkgtDVASFVKLILG 289
3ENM_A       272 DFTSQCLKKn---SKERPTY--PELXQHPFFTLHESkgtDVASFVKLILA 316
gi 34784599  290 DFTSKCLKKn---SKERPTY--PELMQHPFFVLHESkntDVASFVKRILG 334
gi 47939296  293 DFTSQCLRKn---STERPTY--TELMQHPFFTLHDSkdtDVASFVKTILG 337
gi 5101687   282 DFIAVCLQKe---YMARPNY--EQLLKHSFIVEHLQrntDISEFVARILD 326
gi 70570148  303 DFCRCCLNKd---PSKRPNY--RELEDHVFVQKHLHe--DVRSISSFITL 345
gi 156375514 295 DFVTKSLIKn---YKERPNY--NQLLEHPFIKVHMGrnvDVASWLAPFLI 339
gi 115720219 290 DFINKWCSSvpipPHGHGILwsAQIQQMVSSEPAAFs--TAPAAVSTEPA 337
gi 21629476  286 YFVKRCLEKd---YNERPKY--PELLAMPFMEQARNe--KQFSMARFINE 328
gi 83318911  354 DFVNKCLLKd---YHLRPKY--PELLKHPFVSEAHEt--DIADFISLILD 396
gi 24638466  300 DFTAQCLRKn---PAERMSY--LELMEHPFFTLHKTkktDIAAFVKEILG 344

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