1S9J,1S9I,1S9I


Conserved Protein Domain Family
PKc_MEK

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cd06615: PKc_MEK 
Click on image for an interactive view with Cn3D
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase
PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK 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: 132946
View PSSM: cd06615
Aligned: 10 rows
Threshold Bit Score: 552.042
Threshold Setting Gi: 167522000
Created: 4-Apr-2007
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                ##### # #            # #                             #               ###
1S9J_A         6 DDFEKISELGAGNGGVVFKVSHKPsgLVMARKLIHLEIKPAIRNQIIRELQVLHECnSPYIVGFYGAFYSDGEISICMEH 85
1S9I_B        16 DDFERISELGAGNGGVVTKVQHRPsgLIMARKLIHLEIKPAIRNQIIRELQVLHECnSPYIVGFYGAFYSDGEISICMEH 95
gi 73620960   85 EDLEKLGELGSGNGGVVMKVRHTHthLIMARKLIHLEVKPAIKKQILRELKVLHECnFPHIVGFYGAFYSDGEISICMEY 164
gi 21542135   71 DMLQTEGELGHGNGGVVNKCVHRKtgVIMARKLVHLEIKPSVRQQIVKELAVLHKCnSPFIVGFYGAFVDNNDISICMEY 150
gi 70570143   64 SDFTKKGELGAGNGGVVHLVVHNAtgFVMARKLIHLEVKQAILNQITRELQVLHDCrSPYIVGYYGTFYSDGEISICMES 143
gi 115738296  85 DDFEVLKELGAGNGGVVTKVKHKMsgMVMARKLIKLEIKPAIRNQIIRELKVLHECnSPYIVGFFGAYYSDGEICICMEN 164
gi 156396872  37 DDFEKITELGAGNGGVVTKVLHKPtgLIMARKLIHLEVKPAIRTQIIRELKVLHDCnSPYIVGFFGAFYSDGEISICMEH 116
gi 196001281  70 EDFETLCELGAGNGGVVTKVRHTPsgLIMARKLIHLEIKAAVRNQIIRELKILHECnSPYIVGFYGAFYSDGEISICMEH 149
gi 167522000  78 TDLRELVVLGRGNGGSVCKVLHVKsnIIMARKSIHLEIRPEVRNQILRELRILHKCsSPHIIGFYGSFWHDGEINILMEY 157
1S9I_A        16 DDFERISELGAGNGGVVTKVQHRPsgLIMARKLIHLEIKPAIRNQIIRELQVLHECnSPYIVGFYGAFYSDGEISICMEH 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #  ## ##                                        # ## #          #               
1S9J_A        86 MDgGSLDQVLKka--gRIPEQILGKVSIAVIKGLTYLREkHKIMHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 163
1S9I_B        96 MDgGSLDQVLKea--kRIPEEILGKVSIAVLRGLAYLREkHQIMHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 173
gi 73620960  165 MDgGSLDLILKra--gRIPESILGRITLAVLKGLSYLRDnHAIIHRDVKPSNILVNSsGEIKICDFGVSGQLIDSMANSF 242
gi 21542135  151 MDgLSLDIVLKkv--gRLPEKFVGRISVAVVRGLTYLKDeIKILHRDVKPSNMLVNSnGEIKLCDFGVSGMLIDSMANSF 228
gi 70570143  144 MDaGSLDLVLKka--rKIPEIYLGKVSKAVILGLKYLREeRSIIHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 221
gi 115738296 165 MDgGSLDQVMKsapkgRIPENILGKVTVAVLRGLIYLRDvHDIMHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 244
gi 156396872 117 MDgGSLDLILKka--gRIPEDILGKISIAVLKGLCYLREiHQIIHRDVKPSNILVNSrGEIKMCDFGVSGQLIDSMANSF 194
gi 196001281 150 MDaGSLDKVMKka--rRIPEPILGKIAIAVIKGLTYLREkHKIMHRDVKPSNILVNSrGEIKMCDFGVSGQLIDSMANSF 227
gi 167522000 158 MDgGSLDAVVRri--gRIPENVLAEITYCILDGLVYLRDkLSIMHRDIKPSNVLVSSdGDCKLCDFGVSGELHNSLANTF 235
1S9I_A        96 MDgGSLDQVLKea--kRIPEEILGKVSIAVLRGLAYLREkHQIMHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1S9J_A       164 VGTRSYMSPERLQGtHYSVQSDIWSMGLSLVEMAVGRYPIPPPD--AKELELMFgcqvegdaaetpprpr----tpgrpl 237
1S9I_B       174 VGTRSYMAPERLQGtHYSVQSDIWSMGLSLVELAVGRYPIPPPD--AKELEAIFgrpvvdgeegephsisprprppgrpv 251
gi 73620960  243 VGTRSYMSPERLQGtHYSVQSDIWSLGLSLVEMAIGMYPIPPPN--TATLESIFadnaeesg------------------ 302
gi 21542135  229 VGTRSYMAPERLTGsHYTISSDIWSFGLSLVELLIGRYPVPAPS--QAEYATMFnvaeneieladsl----------eep 296
gi 70570143  222 VGTRSYMAPERLQGsKYTILSDIWSLGLSLIEMAIGRFPIPPPT--ASQIAAIFntevsggsgk---------------- 283
gi 115738296 245 VGTRSYMSPERLQGtHYTVQSDIWSLGLSLVEMAIGRYPIPAPD--ETALANLFgyelqagetknirk---------trv 313
gi 156396872 195 VGTRSYMSPERLQGnQYTIQSDIWSFGLSLVEMAIGRYPIPPPD--PQEIEKVLsrepssmaspmsvgrl----ppgvrp 268
gi 196001281 228 VGTRSYMSPERLTGsQYTVHSDIWSFGMSLVEMAIGRYPIPPPDneSLNQEIANdefspasvappg-------------r 294
gi 167522000 236 VGTRSYMSPERLQGqRYAVESDLWSLGLSLLEMATGVFPIPAENl-KKGLAPMHpppdkplea----------------- 297
1S9I_A       174 VGTRSYMAPERLQGtHYSVQSDIWSMGLSLVELAVGRYPIPPPD--AKELEAIFgrpvvdgeegephsisprprppgrpv 251
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1S9J_A       238 ssygmdsrppMAIFELLDYIVNEPPPKLPSGv-FSLEFQDFVNKCLIKnPAERADLKQLMVHAFI--KRSDAee-vDFAG 313
1S9I_B       252 sghgmdsrpaMAIFELLDYIVNEPPPKLPNGv-FTPDFQEFVNKCLIKnPAERADLKMLTNHTFI--KRSEVee-vDFAG 327
gi 73620960  303 --qptdepraMAIFELLDYIVNEPPPKLEHKi-FSTEFKDFVDICLKKqPDERADLKTLLSHPWI--RKAELee-vDISG 376
gi 21542135  297 nyhppsnpasMAIFEMLDYIVNGPPPTLPKRf-FTDEVIGFVSKCLRKlPSERATLKSLTADVFFt-QYADHddqgEFAV 374
gi 70570143  284 apnphdvarpMAIFELLDYIVNEPAPKLPQGi-FEKDFCDFVASCLKKePKERSDLGELMKAPFI--KNVSLtq-yEFAK 359
gi 115738296 314 ggvfsdsprpMAIFELLNYIVEEHPPRLPSRa-FSEEFVDFVDVCLIKnPNERADLKKLKVHTFA--IMSEEar-vDFAG 389
gi 156396872 269 psgvnnetrpMAIFELLDYIVNEPPPILPGAh-FSPEFCEFVQKCLVKnPKQRADLTYLMTHKFI--AKADKsn-vDFAK 344
gi 196001281 295 avsgddapkpMAIFELLDYIVNQPPPRLPSGgvFSKEFQEFVDCCLQKdPKERPDLYELSKKPFI--QKWEAev-vDIAG 371
gi 167522000 298 --hapdatqsMAIFELLANIVESEPPRLPDDagFSDSFINFIDACLKRePSERMPLAELIQHPWLedMRASQp--vNMAE 373
1S9I_A       252 sghgmdsrpaMAIFELLDYIVNEPPPKLPNGv-FTPDFQEFVNKCLIKnPAERADLKMLTNHTFI--KRSEVee-vDFAG 327

                 ....*.
Feature 1              
1S9J_A       314 WLCSTI 319
1S9I_B       328 WLCKTL 333
gi 73620960  377 WVCKTM 382
gi 21542135  375 FVKGTI 380
gi 70570143  360 WVCSTM 365
gi 115738296 390 WICATM 395
gi 156396872 345 WISQFL 350
gi 196001281 372 WICKVM 377
gi 167522000 374 WVRSTM 379
1S9I_A       328 WLCKTL 333

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