Conserved Protein Domain Family
7tmF_FZD4

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cd15038: 7tmF_FZD4 
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors
This group includes subfamily 4 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its 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: 320166
View PSSM: cd15038
Aligned: 10 rows
Threshold Bit Score: 518.549
Threshold Setting Gi: 156209604
Created: 14-Nov-2013
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 GLYSRSAKEFTDIWMAVWASLCFISTTFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgRERISCDfee-a 287
gi 17433072  195 GLYNRLSKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFCYPERPIIFLSMCYNIYSIAYIVRLTVgRERISCDfee-a 273
gi 17433062  197 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgRERISCDfee-a 275
gi 405951309 199 AAFTTEDKYFADIWMSIWSGLCFVSTLLTILTFVIDSQRFKYPERPIIFLSMCYNIYSIAYIVRLIAgRESIACDrdtas 278
gi 556110495 199 DAFTSKDKLFADVWMAIWAGLCFVSTFFTVLTFLIDSQRFKYPERPIIFLSMCYNIYSIAYIVRLLAgRQSIACDtdsqs 278
gi 375269595 207 FLFSQSEKRFTEIWMAIWAGLCFLTTAMTVLTFAIDTVRFRYPERPIIFLSICYNVFSIAYIVRLIAgRAVIACDdd--g 284
gi 229297616 215 GNFTPEEKRFADIWMAVWAGLCFLSTMFTVLTFLIDTARFRYPERPIIFLSMCYNIYSIAYIVRLVVgRKAISCDse--d 292
gi 443708550 206 DLFTESDKEFADIWMFIWALLCFVSTLFTALTFAIDAGRFRYPERCIVFLSLCYNMCSIAYIVRLAVgRYAISCGldaat 285
gi 156209604 179 GIFKTSDKETMDIWITIWSIFCFISTTITLTTFLIETGRFKYPERSIIWLALCYNFYSLSYIIRLGAgRQAISCDtdptt 258
gi 215491258 223 ILFTQENKRFAEIWTSVWACLCFLSTLFTLGTFFVDSRRFHYPERGIIYMSGCYNVYCVAYFVRLLLgRSSVSCHldsqh 302
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         #                                                                              
gi 17433026  288 aEPVLIQEGlKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGhEAIEMHSSYFHIAAWAIPAVKTIVILIMRl 367
gi 17433072  274 aEPVLIQEGlKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGhEAIEMHSSYFHIAAWAIPAVKTIVILIMRl 353
gi 17433062  276 aEPVLIQEGlKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGhEAIEMHSSYFHIAAWAIPAVKTIVILIMRl 355
gi 405951309 279 kTSILIQEGlENTDCAIVFLLLYYFGSAAALWWVILTLTWFLSAGLKWThEAIQLHSSYFHLAAWALPAIETIIILVMRe 358
gi 556110495 279 gKSILIQEGlENTDCAIVFLLLYFFGTASSLWWVVLTFTWFLSAGLKWGhEAIQLHSSYFHLFAWALPAIKTIVILVMRd 358
gi 375269595 285 iAQFLIQEGlENTGCAATFLILYFFGMASSIWWVILAFTWFLAAGLKWGhEAIQMNSSYFHVAAWGIPFVKTVIILVMRv 364
gi 229297616 293 gQAFLIQQGlENTGCAIVFLFLYFFGMASSIWWVILTLTWFLSAGLKWGhEAIEMHSSYFHLATWSIPAIKTIVIFVMKq 372
gi 443708550 286 qKPILIQEGlDNSDCSIVFLLQYYFGTASCTWWVLLTVTWFLAAGLKWSsEAIQRHATTFHVIAWALPAVKTIVILVIRn 365
gi 156209604 259 hVKFHIQDGlRNTGCAIVFLIQYFFCMAATIWWVVLALTWFLAAGMKWGcEAIGSYAKLFHIIAWILPCIKTIFILITRk 338
gi 215491258 303 eVSILIQEGvDNINCTVVFMLLYYFGMASATWWVVLTVTWFLSAGLRWShERVQKHMTAFHFFAWVLPAVQTIVILVMRv 382
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           #    # #  ##    #                                                            
gi 17433026  368 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQkd-gTKTDKLERLMVKIGVFSVLYTV 446
gi 17433072  354 VDADELTGLCYVGNQNIDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQkd-gTKTDKLERLMVKIGVFSVLYTV 432
gi 17433062  356 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQkd-gTKTDKLERLMVKIGVFSVLYTV 434
gi 405951309 359 VDADELTGICYVGNQNTQTLLGFSVAPSLVYLVVGVAFLIAGFIALLRVQSQDRvn-gVKSAKIENLMIRVGIFSLLYTI 437
gi 556110495 359 VDADELTGICYVGNQSTQMLLGFGVAPLIVYLILGTAFLIAGFVALFRIRKQVRcd-gVKTDKLEVLMVRIGIFSVLYTV 437
gi 375269595 365 VDADELTGMCFVGNSSLEALTGFVIAPLFTYLAVGTLFLLGGFISLFKIRSVMKnd-gTKTDKLERLMVKVGLFSVLYTV 443
gi 229297616 373 VDADELTGLCFVGNQNLDALTGFVVAPLFTYLVVGTSFLLAGFVSLFRIRNFMKnd-gTKTDKLERLMVKIGVFSVLYTV 451
gi 443708550 366 IDADELTGMCYVGNQRLDTLLGFVIVPLSVYLFIGVIFIILGFIAMFRVRRQVRre-gHKTEKLEVLMVRIGVFSVLYTV 444
gi 156209604 339 VDGDELTGLCFVGNQDLIALAAFVLGPQFTYLIIGTLFLIAGFVALFRIRTTVQrggqAKTDKLERLIVRIGIFSVLSTV 418
gi 215491258 383 VDADELTGTCFVGNQNRHALLGFVVLPSIVYLLVGAIFLAWGIVTMMRSRDSLGh--aPKADKLEIIMIRVGIFAVLYMV 460
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
Feature 1                       #  ##          #    #  ##                            
gi 17433026  447 PATCVIACYFYEISNWAlFRYs-----aDDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 509
gi 17433072  433 PATCVIACYFYEVSNWNvFRYt-----aDDSNMAVEMLNIFMSLLVGITSGMWIWSAKTLHTWQKCTN 495
gi 17433062  435 PATCVIACYFYEISNWAvFRYs-----aDDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 497
gi 405951309 438 PAAIVIACLLYEYASRDsWYLrdt--ihSEPKMEIFMLKVFMTLVVGITSGMWIWSSKTINSWRNFAV 503
gi 556110495 438 PATCVIGCLLYEYLNRSsWYLys---pqTSPNIEIFMLKLFMSLVVGITSGMWIWSAKTVSSWKNFFK 502
gi 375269595 444 PATIVVACFFYEHSNRIiWMDg-----eATPNIEVFMLKIFMSLVVGITSGMWIMSAKTMRSWRRFIE 506
gi 229297616 452 PATCVIACYFYEHSNRElWRYs-----sAKPNIELYMLKIFMSLVVGITSSMWIWSAKTVSSWANCTR 514
gi 443708550 445 PAMCVIGCYLYEYLNRSlWHSvav-agqHRPNMEVFMLRIFMALAVGMTSGMWVWSAKTLSSWRNLFA 511
gi 156209604 419 PATAVIACYFYEYANKEyWYYgqrdgavAEPNFSIFMLKVFMSLFTGVITGMWIWSHKTMNTWRAFYY 486
gi 215491258 461 PAACVLASYIYEYSYRDeWLAag---saFRPNLEVFTLRIFMSLVVGITTGLWTWSSRVPLAACRRPM 525

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