Conserved Protein Domain Family
7tmB2_GPR64

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cd15444: 7tmB2_GPR64 
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B secretin-like receptors of seven-transmembrane G protein-coupled receptors
GPR64 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR97, GPR112, GPR114, and GPR126. GPR64 is mainly expressed in the epididymis of male reproductive tract, and targeted deletion of GPR64 causes sperm stasis and efferent duct blockage due to abnormal fluid reabsorption, resulting in male infertility. GPR64 is also overexpressed in Ewing's sarcoma (ES), as well as upregulated in other carcinomas from kidney, prostate or lung, and promotes invasiveness and metastasis in ES via the upregulation of placental growth factor (PGF) and matrix metalloproteinase (MMP) 1. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.
Statistics
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PSSM-Id: 320560
View PSSM: cd15444
Aligned: 4 rows
Threshold Bit Score: 478.166
Threshold Setting Gi: 642114086
Created: 11-Nov-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative polypeptide ligand binding pocket [polypeptide binding site]
Evidence:
  • Comment:based on mutagenesis of human glucagon receptor (GCGR), and modeling studies of GCGR and other related class B GPCRs
  • Comment:Residues in the globular N-terminal extracellular domain and the extracellular loops of the 7TM domain may also be involved in ligand binding.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #   #                                          #  ##  #         #      # 
gi 229462874  625 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDypSKILIQLCAALLLLNLVFLLDSWIAlyk-mqGLCISVAVFLHY 703
gi 637282377  929 MLILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDypSKILIQLCVALLLLNLVFLLDSWIAlyk-ikGLCISVAVFLHY 1007
gi 512825306  704 TLILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDypSKILMQLCAALILLNLTFLINPWIAlynnipGLCISAAAFLHY 783
gi 642114086  957 ATILTYITYIGCGISAIFLSVTLLTYLAFGKLRKDipSKILIQLCVALLFLNLVFLVDAWLAlypdavGLCISTAWFLHY 1036
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 229462874  704 FLLVSFTWMGLEAFHMYLALVKVFNTYirKYILKFCIVGWGVPAVVVTIILTISpdnyglgsy-gkfpngspdDFCWINn 782
gi 637282377 1008 FLLVSFTWMGLEAFHMYLALVKVFNTYvrKYILKFCIVGWGLPAIVIAIVLAISpdnyglgsy-gklpngsadEFCWINn 1086
gi 512825306  784 FLLVSITWMGLEAFHMYFSLVKVFNTYvrKYILKFCIVGWGVPAVVVAIILAVNkdlygfqsk-gkypngdsdDICWIA- 861
gi 642114086 1037 FLLASFTWMGLEAVHMYLALVKVFNTYikRYMLKFSLVGWGVPLLVVIVVIAVDknnyglvsygkysdnsptdDFCWLKn 1116
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1            ## # #                                                      #  #           # 
gi 229462874  783 NAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKkkqlgaqrkTSIQDLRSIAGLTFLLGITWGFAFFAWGPvNVTFMY 862
gi 637282377 1087 NTVFYITVVGYFCMIFLLNISMFIVVLIQLCRIKKkkqlgaqrkTSIQDLRSVAGLTFLLGITWGFAFFAWGPvNLIFMY 1166
gi 512825306  862 DIIFYITVVGYYGIVFLMTISMFIVVILQLCRIKKqkqlgfqkkITLQDMRSVAGITFLLGITWGLAFFSWGPgGVVIVY 941
gi 642114086 1117 NIAFYVSVVAYFCVIFLLNLSMFVVVMVQLCRIKSqnphnmrhrNGLQDLRSVVGITLLLGLTWGFAFFAWGPvNLAFMY 1196
                         250       260       270
                  ....*....|....*....|....*....|..
Feature 1           #                             
gi 229462874  863 LFAIFNTLQGFFIFIFYCVAKeNVRKQWRRYL 894
gi 637282377 1167 LFAIFNTLQGFFIFVFYCVAKeNVRKQWRRYL 1198
gi 512825306  942 LFTIFNTLQGFFIFIFYCVAKeNVRKQWKRYL 973
gi 642114086 1197 LFAIFNSFQGFFIFLFHCAVKeNVRRQWRTYL 1228

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