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
Aligned: 11 rows
Threshold Bit Score: 521.6
Created: 4-Apr-2007
Updated: 2-Oct-2020
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.
  • 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:
Feature 1                ##### # #            # #                              #               ##
3FME_A         7 DDLEPIMELGRGAYGVVEKMRHVPsgQIMAVKRIRATVNsqEQKRLLMDLDISMRTVDCPFTVTFYGALFREGDVWICME 86  human
3ENM_A        34 DDLEPIXELGRGAYGVVEKXRHVPsgQIXAVKRIRATVNsqEQKRLLXDLDISXRTVDCPFTVTFYGALFREGDVWICXE 113 human
AAH57716      52 DDLEPIEELGRGAYGVVEKMRHVPseQIMAVKRIRATVNsqEQKRLLMDLDISMRTVDCHFTVTFYGALFREGDVWICME 131 African clawed ...
AAH71285      55 DDLEQIGELGRGAYGVVDKMRHVPsgVIMAVKRIRATVNtqEQKRLLMDLDISMRTVDCFYTVTFYGALFREGDVWICME 134 zebrafish
CAB45101      44 DSLEKICDLGRGAYGIVDKMRHKQtdTVLAVKRIPMTVNirEQHRLVMDLDISMRSSDCPYTVHFYGAMYREGDVWICME 123 fruit fly
BAE06545      65 DDLTIVEELGRGAYGVVDKMKHKSteTIIAVKRIRATLNtqEQKRLLMDLDVSMRSVDCDYTVTFYGALFRQGDVWICME 144 Ciona intestinalis
XP_001630125  56 DDLQEIRELGHGAYGYVYEMLHVPtsTVMAVKKIRANVNstEQKRLLMDLDISMRVSDYPYTVHFYGALFREGDVWICME 135 starlet sea ane...
XP_790720     51 RDMIVIENLGRGAYGIVDKTRHEPteSIMAVKKMRAQVNstEDKRILMDMDVAMRSSDCVYTVEFYGALFQEGDVWICME 130 purple urchin
AAA96067      48 TDLVVLEELGKGGYGIVEKMQHRQsgIIMAVKRIKSSINdqSQKQMLNELDACRRSDCCPQMVRFYGAMFREGDVWICME 127 nematode
CAJ38794     118 DDFQFVDTLGRGAYGVVDKMKHPPtgTIVAVKRLAYSLEsaDYKSLLMDLNVSLRTGHCPNIVHFYGALFGRGDVWIFME 197 Dumeril's clam ...
P46734        62 DDLVTISELGRGAYGVVEKVRHAQsgTIMAVKRIRATVNsqEQKRLLMDLDINMRTVDCFYTVTFYGALFREGDVWICME 141 human
Feature 1        ## ## ##                                           # ## #          #            
3FME_A        87 LMDTSLDKFYKQVIdkg-qtIPEDILGKIAVSIVKALEHLHSkLSVIHRDVKPSNVLINalGQVKMCDFGISGYLVDDVA 165 human
3ENM_A       114 LXDTSLDKFYKQVIdkg-qtIPEDILGKIAVSIVKALEHLHSkLSVIHRDVKPSNVLINalGQVKXCDFGISGYLVDDVA 192 human
AAH57716     132 LMDTSLDKFYKDVIdkg-ltIPEDILGKIAVSIVKALEHLHSkLSVIHRDVKPSNVLINkeGQVKMCDFGISGYLVDSVA 210 African clawed ...
AAH71285     135 LMDTSLDKFYKQVHekg-ktIPEDILGKITVSIVKALEHLHSnLSVIHRDVKPSNVLINmqGQVKMCDFGISGYLVDSVA 213 zebrafish
CAB45101     124 VMSTSLDKFYPKVFlhd-lrMEESVLGKIAMSVVRALHYLHAqLKVIHRDVKPSNILINraGQVKICDFGISGYLVDSIA 202 fruit fly
BAE06545     145 VMDTSLDQFYKKVKdrg-lkTGEDVLGIIAVSIVKALRYLQEtLHVIHRDVKPSNVLLNknGQVKLCDFGISGQLVDSLV 223 Ciona intestinalis
XP_001630125 136 LMKTSLYDLYKQVFskpdrrIPEEVLGKIAVSVVSALEYLHSnLKVIHRDVKPSNILVDerGNFKLCDFGISGQLVDSLA 215 starlet sea ane...
XP_790720    131 VMDTCLDKLYKNKLkpqkifVPENILSRISFSIVSALKYLQTrLKVIHRDVKPSNVLANhnGKIKLCDFGISGQLVNSMA 210 purple urchin
AAA96067     128 VMDTSLDKFYRHAYkig-khIPEPFIGKMALSVIEGLNFMKEqLNLIHRDVKPSNILLNrhGQVKICDFGISGHLTNSMA 206 nematode
CAJ38794     198 VMDTSLDKFYKKVYqhk-mtIKEPALAKITLGVMMGLSYLKEkLSVIHRDVKPSNILANrqGNIKLCDFSVSGNLIDSLS 276 Dumeril's clam ...
P46734       142 LMDTSLDKFYRKVLdkn-mtIPEDILGEIAVSIVRALEHLHSkLSVIHRDVKPSNVLINkeGHVKMCDFGISGYLVDSVA 220 human
Feature 1                                                                                        
3FME_A       166 KDiDAGCKPYMAPERINPELnqkGYSVKSDIWSLGITMIELAilRFPYDSWgtPFQQLKQVVEEPSPQLPADk-FSAEFV 244 human
3ENM_A       193 KDiDAGCKPYXAPERINPELnqkGYSVKSDIWSLGITXIELAilRFPYDSWgtPFQQLKQVVEEPSPQLPADk-FSAEFV 271 human
AAH57716     211 KTmDAGCKPYMAPERINPELnqkGYSVKSDIWSLGITLIELAilRFPYDSWgtPFQQLKQVVEEPSPQLPADk-FSAEFV 289 African clawed ...
AAH71285     214 KTmDAGCKPYMAPERINPETnqkGYNVKSDIWSLGITMIELAilRFPYDSWgtPFQQLKQVVEGPSPQLPADr-FSADFV 292 zebrafish
CAB45101     203 KTiDAGCKPYMAPERIDPQGnpaQYDIRSDVWSLGIGMIEMAtgRYPYDNWrtPFEQLRQVVEDSPPRLPEGt-FSPEFE 281 fruit fly
BAE06545     224 KTiDAGCKPYMAPERIDPAQnqqGYDVKSDVWSLGITMIEVAtgDFPYDTWrnPFQQLKQVVEDPSPKLPANt-FSLELD 302 Ciona intestinalis
XP_001630125 216 KTvDAGCKPYMAPERINPDRdmkGYDIRSDIWSLGITMIELAtgKFPYTQWktPFEQLKQVVHEPSPSLPEGp-FSLNFR 294 starlet sea ane...
XP_790720    211 KTqDAGSRQYMAPERIDPDMsakGYDVKSDVWSFGITMIEIAtnAYPYERWhdMFQQLTQVVKGTSPALPKEk-FSEDIQ 289 purple urchin
AAA96067     207 KTvQAGCKPYMPPERIDGETk-sAYDVRADVWSLGITIIEIAvgTHPYANWktPFEQLKQVVKEPPPKLPMEsgFSVDCQ 285 nematode
CAJ38794     277 KT-KIGARPYMAPEKVNPDGe-qHFDVRSDIWSLGXSLIELAtgKFPYATWktPFEQIKQVVQGPSPTLPNEg-FSPQIQ 353 Dumeril's clam ...
P46734       221 KTmDAGCKPYMAPERINPELnqkGYNVKSDVWSLGITMIEMAilRFPYESWgtPFQQLKQVVEEPSPQLPADr-FSPEFV 299 human
Feature 1                                                          
3FME_A       245 DFTSQCLKKn---SKERPTY--PELMQHPFFTLHESkgtDVASFVKLILG 289 human
3ENM_A       272 DFTSQCLKKn---SKERPTY--PELXQHPFFTLHESkgtDVASFVKLILA 316 human
AAH57716     290 DFTSKCLKKn---SKERPTY--PELMQHPFFVLHESkntDVASFVKRILG 334 African clawed frog
AAH71285     293 DFTSQCLRKn---STERPTY--TELMQHPFFTLHDSkdtDVASFVKTILG 337 zebrafish
CAB45101     282 DFIAVCLQKe---YMARPNY--EQLLKHSFIVEHLQrntDISEFVARILD 326 fruit fly
BAE06545     303 DFCRCCLNKd---PSKRPNY--RELEDHVFVQKHLHe--DVRSISSFITL 345 Ciona intestinalis
XP_001630125 295 DFVTKSLIKn---YKERPNY--NQLLEHPFIKVHMGrnvDVASWLAPFLI 339 starlet sea anemone
XP_790720    290 DFINKWCSSvpipPHGHGILwsAQIQQMVSSEPAAFs--TAPAAVSTEPA 337 purple urchin
AAA96067     286 YFVKRCLEKd---YNERPKY--PELLAMPFMEQARNe--KQFSMARFINE 328 nematode
CAJ38794     354 DFVNKCLLKd---YHLRPKY--PELLKHPFVSEAHEt--DIADFISLILD 396 Dumeril's clam worm
P46734       300 DFTAQCLRKn---PAERMSY--LELMEHPFFTLHKTkktDIAAFVKEILG 344 human

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