Conserved Protein Domain Family
7tmF_FZD1

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cd15247: 7tmF_FZD1 
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors
This group includes subfamily 1 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of G-protein coupled receptors. 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: 320375
View PSSM: cd15247
Aligned: 4 rows
Threshold Bit Score: 683.692
Threshold Setting Gi: 17432982
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 17433059  218 PCEVGKVHGlMYFAPEELNFARIWIGIWSVLCCASTLFTVLTYLVDMKRFSYPERPIIFLSGCYTMVAIAYIAGFLLEDK 297
gi 341941091 294 PCEPTKVYGlMYFGPEELRFSRTWIGIWSVLCCASTLFTVLTYLVDMRRFSYPERPIIFLSGCYTAVAVAYIAGFLLEDR 373
gi 17432982  248 PCEPGRLYGlMYFGPEELRFSRTWIGIWSVLCCASTLFTVLTYLVDMKRFSYPERPIIFLSGCYTAVAVAYIAGFLLEER 327
gi 542195194 212 PCEPKRSHGmMYFSEEELKFARIWIGIWSVLCCASTLFTVLTYLVDMKRFSYPERPIVFLSGCYTMVSIAYIAGFLLEDK 291
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                  #                                                                     
gi 17433059  298 VVCNERFaEDGYKTVAQGtKKEGCTFLFMMLYFFSMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAIK 377
gi 341941091 374 VVCNDKFaEDGARTVAQGtKKEGCTILFMMLYFFSMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAIK 453
gi 17432982  328 VVCNERFaEDGSRTVAQGtKREGCTILFMMLYFFGMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAIK 407
gi 542195194 292 VVCNDKF-DNDIKTVVQGtKKEGCTILFMMLYFFSMASSIWWVILALTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAIK 370
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    #    # #  ##    #                                                   
gi 17433059  378 TITILAVGQVDGDTLSGVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIG 457
gi 341941091 454 TITILALGQVDGDVLSGVCFVGLNNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIG 533
gi 17432982  408 TITILALGQVDGDVLSGVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIG 487
gi 542195194 371 TITILAVGQVDGDVLSGVCFVGINSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIG 450
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                               #  ##                               #    #  ##           
gi 17433059  458 IFSVLYTVPATIVIACYFYEQAFREQWEKSWISQSCKTYAIPCPst-------gHPPMSPDFTVFMIKYLMTLIVGITSG 530
gi 341941091 534 VFSVLYTVPATIVIACYFYEQAFRDQWERSWVAQSCKSYAIPCPhlqggggvppHPPMSPDFTVFMIKYLMTLIVGITSG 613
gi 17432982  488 IFSVLYTVPATIVIACYFYEQAFREQWERSWVTQSCKSYAIPCPnnh----sshHPPMSPDFTVFMIKYLMTLIVGITSG 563
gi 542195194 451 IFSVLYTVPATIVIACYFYEQAFREQWERTWISQTCKTYAVPCPah-------sHPNMSPDFTVFMIKYLMTLIVGITSG 523
                        330       340
                 ....*....|....*....|....*...
Feature 1                                    
gi 17433059  531 FWIWSGKTLNSWRKFYTRLTNSKQGETT 558
gi 341941091 614 FWIWSGKTLNSWRKFYTRLTNSKQGETT 641
gi 17432982  564 FWIWSGKTLNSWRKFYTRLTNSKQGETT 591
gi 542195194 524 FWIWSGKTLNSWRRFYTRLANSKQGETT 551

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