Conserved Protein Domain Family
7tmF_FZD4_9_10-like

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cd15909: 7tmF_FZD4_9_10-like 
class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G protein-coupled receptors
This group includes subfamilies 4, 9 and 10 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.
Statistics
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PSSM-Id: 320575
View PSSM: cd15909
Aligned: 16 rows
Threshold Bit Score: 459.848
Threshold Setting Gi: 49781255
Created: 24-Jun-2014
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative ligand binding site [chemical binding site]
Evidence:
  • Comment:based on sequence similarity to Human smoothened receptor bound to an antitumor agent.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         #        #                                                 #                   
gi 17433026  209 GLYSRSAKEFTDIWMAVWASLCFISTTFTVLTFLIDSSrfsypERPIIFLSMCYNIYSIAYIVRLTVgrERISCDfeeaa 288
gi 375269597 224 VYFQRSDKDFTEMWMGVWAILCFVCTSITVLTFLIDRGrfkypERPIIFLSMCYNIYSITYVVRLIVgpQAVACEktssg 303
gi 156217655 209 LMFSSNNKRFANVWISVWSVLCFISTAVTVLTFVIDTSrfkypERPIIFLSLCYNLYSLGYIVRVTAgrNEVICDetesf 288
gi 229284331 182 VFFSRQDKEFVEIWMGIWSVVCVISTSVVILTFMIDSRrfrypERPIIFMAVCYFFYSIGFILRLGLgrETISCDmdrge 261
gi 555691473 141 VMYRFTDKKFAEIWMILWAVLCLVSTLFTFLTFILDTTrfeypERPIIYLSMCCLVYSCGYIIRFARglSDVSCIesrhq 220
gi 402591376  95 GMFDVSKKEFARFWMLLWASINLGVTAFTVLTFIIDRQrfrfpERSIFYLSACYMLFSLPPLSRAVFpyERIVCDklptg 174
gi 395133426 229 VFYTQKHKNFAYTWMAIWASLCIASTLFTILTFCIDPRrfrypTRPVIFMAFCYLIYALSYFIPLFIprEKIICKsdvqg 308
gi 316968833  45 WMFTEEQKNFAQVWMAVWASVCFLSTGFTVMTFLLDTSrftypKRPIVFIAICYCATSVGYLLRLLVgrEAAGCQqldsg 124
gi 556516042 250 LFYRPGDKKFARAWLLGWSILCVASSALTFFTFFVDGSrlqypERPVLYLAACYFVIGVGYILQYSLgpERVTCRslqtg 329
gi 159498732 190 VQFNAHDKVFANIWLLGWSVLCFFSCLLTIIVFSCNTNrflypEKPIVFLSICYFFYASGNLFGAILgrNVVACRafndk 269
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 17433026  289 ep-------vliqeglKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGhEAIEMHSSYFHIAAWAIPAVKTIV 361
gi 375269597 304 vp-------ylimeglDTTGCTIVFLIQYYFFMASSIWWVILTLTWFLAAGMKWGyEAIAAYSSYYHVVAWALPALKTII 376
gi 156217655 289 vi-------ragmniaDHACCSVVFLLLYYFGMASAVWWVVLTFAWFLAAGRKWGqEAIERKATYFHAVAWTVPAIQTIM 361
gi 229284331 262 py--------liqeglESTGCTIVFLILYFFGMASSLWWVILTMTWFLAAGLKWGqEAIEAHSSYFHLAAWAVPAVKTIV 333
gi 555691473 221 vs-------yviqeglENTWCVVVFLILYYFNMAGCIWWVILTSTFYFSAAKKWSrEALQKANNYFHVISWTLPAVLTTI 293
gi 402591376 175 qt-------flivgtlDNTSCVMSFILTYYFSVASSLWWLMLTFTWYLSAARKWVpEGIDAWSSYLHLVAWALPAILTIA 247
gi 395133426 309 dl--------mvvngmESTLCVIIFLVQYYFGIASHVWWLILTFTWYLAASRKWVlEAINSIACYFHLFAWAVPAVLTVV 380
gi 316968833 125 qs-------vlvshslSNAVCVVTFILLYYFGLASAVWWLILTMTWYLAAGRKWSqEAIARLSSTFHIIAWVIPASLTVT 197
gi 556516042 330 dsnaaemqkyllmggqESAWCTVGFLISYYFGMASNFWWVMLSLAWYLSTSRKWGhEGVESVSSVFHMFAWALPAIQAIL 409
gi 159498732 270 td-------fivgsgrETTWCKINFLMIYFFGSASALWWVVLTITWFLSASRHWGyEAIESISSMLHLVSWAIPALKSIF 342
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                 #    # #        #                                                      
gi 17433026  362 ILIMRlVDADELTGLCYVGnqNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLqkd-----gtkTDKLERLMVK 436
gi 375269597 377 ALAKHrLDADELTGMCYIGnhDPDVLTYYVLVPLFIYFAIGTLFILAGFFYLFRIRKVMkng-----gtnIDKLERLMVR 451
gi 156217655 362 ALIMRkVDADELTGLCYVGnmDYENLANYVLTPLCLYLLVGTFFLLAGFVSLFRIRTVLknk-----etnTDKLEKLIVR 436
gi 229284331 334 VLTLRrVDGDELTGLCYVGnqDQTALTWFVLAPLFTYLLLGTCFILAGFVNLFRIRKVMrhg-----gnsTERLEKLMSR 408
gi 555691473 294 VLTMRrLDGDELTGLCFVGnqDMDSLLTFVLFPNMVFLIIGVYFIIGGFVAMFRIRQDLvsdg----cldVKKFEKLMMK 369
gi 402591376 248 VLTTHkVDANELTGLCSVGnvDPWALFGFIIVPKLIFVVVGSCLIVAGFSSMCRERDSFrrr-----gtdTSKLEKLMVK 322
gi 395133426 381 ILVTGrVDSNELTGMCYVGnhDKWSLLIYIIIPTSFLCLVGEILMLAGFVSVLRIRTNLkthv---ddasVRKLEKLMAK 457
gi 316968833 198 LLVTHeLEASELTSMCFVClhSSSALFGFVVGPVAVFSAIGICFMVAGIVSMVRISREMrfri---cdtdLQKLRKLMTK 274
gi 556516042 410 ILILHkIDADELTGTCYTGfhSETSLMFGVLLPQAICLLLGLLLLSVGFAAVFRVRRKLkapsd-reresRRRLEKSIAK 488
gi 159498732 343 ILILHkIDADELTGQCFVGnsNNKVLWGFVIVPNMIYLFIGIVFLTMGYISLLKVRRSFlqrpdcidtnnLKRLEKLMAK 422
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                 #  ##                                  #    #  ##      
gi 17433026  437 IGVFSVLYTVPATCVIACYFYEISNWAlFRYs-----------------------------aDDSNMAVEMLKIFMSLLV 487
gi 375269597 452 IGIFSVLYTVPATAVIACYFYQRSNMEyWRIvaehapcrplpp--------eegggcapmdySIPSVPVLSVKLFMLLVV 523
gi 156217655 437 IGVFSVLYTIPVSAVIACSFYEYNNMDvWKVrapfntyic-------------rgdqaclenYGPSIEVFIVKYFMLLII 503
gi 229284331 409 IGIFSVFYTVPATCVVACYFYEQQNMStWTT-------------------------------TAQEIPCNNNIAFLLLVG 457
gi 555691473 370 IGIFSILYTLPDICVVGCLFFEWLNFRdWRAaayltpcykfdds-----lnhqqlvdcslekSIPAVEVKVLKIFMSLVI 444
gi 402591376 323 MGIFSALYVIPAITIIICDSYHMFILMqWHPttiacklhgg------------iekghckrpPLPQVELYFLNIFMSLVI 390
gi 395133426 458 IGVFAIFYTVPTVCVLGSNIHEFINMDtWRCmsslt---------------------stlvgSIPTVEIHILKISMSLIV 516
gi 316968833 275 VCVFSLLYVVLTLIVVVCSVYEKFFDEeWLSsqfecrpqsfkdatt-gvglrhcnmsgmgslSPPAVEIYMLKVFISLTI 353
gi 556516042 489 LGVFVVLYTFPMACLLASNLYEYLGQPrWRAalrelntarphcls---prgvawglpechpkDSPSSEAAMLRIFMSFVV 565
gi 159498732 423 IGVFSILYVLPVLCTIVSYIVDAYKMTnFDItlkalfrfspncigrnginwssikcvkilqpVLPSVEMRMLRIFMNLVI 502
                        330       340
                 ....*....|....*....|...
Feature 1                               
gi 17433026  488 GITSGMWIWSAK-TLHTWQKCSN 509
gi 375269597 524 GITSGMWIWSSK-TVQSWQNWLG 545
gi 156217655 504 GITSNMWIWSTK-TFKSWRKFYS 525
gi 229284331 458 CFGTSLWICSNK-TMESWQNFCN 479
gi 555691473 445 GTASGIWVWSPK-TVQLWTKFFK 466
gi 402591376 391 GISTGMWTVSSK-TFHSWQRAIC 412
gi 395133426 517 GVFIAMWVLNSK-TLQTCERKCS 538
gi 316968833 354 GIISSMWIWSKK-TLLMWHHFFC 375
gi 556516042 566 GITSGMWVWANKkTLMSWNRVVF 588
gi 159498732 503 GITSGIWIWGNKkTVKSCISTLR 525

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