Conserved Protein Domain Family
7tmB2_GPR126-like_Adhesion_VIII

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cd15258: 7tmB2_GPR126-like_Adhesion_VIII 
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors
Group VIII adhesion GPCRs include orphan GPCRs such as GPR56, GPR64, GPR97, GPR112, GPR114, and GPR126. GPR56 is involved in the regulation of oligodendrocyte development and myelination in the central nervous system via coupling to G(12/13) proteins, which leads to the activation of RhoA GTPase. GPR126, on the other hand, is required for Schwann cells, but not oligodendrocyte myelination in the peripheral nervous system. 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. GPR97 is identified as a lymphatic adhesion receptor that is specifically expressed in lymphatic endothelium, but not in blood vascular endothelium, and is shown to regulate migration of lymphatic endothelial cells via the small GTPases RhoA and cdc42. GPR112 is specifically expressed in normal enterochromatin cells and gastrointestinal neuroendocrine carcinoma cells, but its biological function is unknown. GPR114 is mainly found in granulocytes (polymorphonuclear leukocytes), and GPR114-transfected cells induced an increase in cAMP levels via coupling to G(s) protein. 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: 320386
View PSSM: cd15258
Aligned: 6 rows
Threshold Bit Score: 338.621
Threshold Setting Gi: 148886621
Created: 25-Jan-2014
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:
Feature 1             #   #                                              #  ##  #         #    
Q86Y34     265 VHILTRISQAGCGVSMIFLAFTIILYAFLRLsrerfksedaPKIHVALGGSLFLLNLAFLVNVGSGskg-sdAACWARGA 343  human
Q8IZF4     245 LAPLTYISLVGCSISIVASLITVLLHFHFRKqsd-----slTRIHMNLHASVLLLNIAFLLSPAFAmspvpgSACTALAA 319  human
Q50DM7     400 KHYLSLLSYVGCVVSALACVVTIAAYLCSRRkpr----dytIKVHMNLLLAVFLLDTSFLLSEPVAltg-seAGCRASAI 474  chimpanzee
Q8IZP9     625 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKirr----dypSKILIQLCAALLLLNLVFLLDSWIAlyk-mqGLCISVAV 699  human
Q86SQ4     861 TKVLTFISYIGCGISAIFSAATLLTYVAFEKlrr----dypSKILMNLSTALLFLNLLFLLDGWITsfn-vdGLCIAVAV 935  human
B7ZCC9    2690 ERILVIITYTGCGISSIFLGIAMVTYIAFHKlrk----dypSKILINLCTALLMLNLAFLVNSWLTsfq-kvGLCITAAV 2764 house mouse
Feature 1        #                                                                             
Q86Y34     344 VFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYfgHYFLKLSLVGWGLPALMVIGTGSANsyglytird--------renrt 415  human
Q8IZF4     320 ALHYALLSCLTWMAIEGFNLYLLLGRVYNIYirRYVFKLGVLGWGAPALLVLLSLSVKssvygpctipvfdswengtgfq 399  human
Q50DM7     475 FLHFSLLACLSWMGLEGYNLYRLVVEVFGTYvpGYLLKLSAMGWGFPIFLVTLVALVDvdnygpiilav---hrtpegvi 551  chimpanzee
Q8IZP9     700 FLHYFLLVSFTWMGLEAFHMYLALVKVFNTYirKYILKFCIVGWGVPAVVVTIILTISpdnyglgsyg------kfpngs 773  human
Q86SQ4     936 LLHFFLLATFTWMGLEAIHMYIALVKVFNTYirRYILKFCIIGWGLPALVVSVVLASRnnnevygke-------sygkek 1008 human
B7ZCC9    2765 ALHYFLLVSLTWMGLEAVHMYFALVKVFNTYipNYILKFCLAGWGIPAITVAIILSVRkdlygt-------------lsp 2831 house mouse
Feature 1                     ## # #                                                      #  # 
Q86Y34     416 sleLCWFRegttMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRatav-kergKNRKKVLTLLGLSSLVGVTWGLAI 494  human
Q8IZF4     400 nmsICWVRs---PVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRErada--psvRACHDTVTVLGLTVLLGTTWALAF 474  human
Q50DM7     552 ypsMCWIRd---SLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPh-------tQKWSHVLTLLGLSLVLGLPWALIF 621  chimpanzee
Q8IZP9     774 pddFCWINn---NAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKkkqlgaqrkTSIQDLRSIAGLTFLLGITWGFAF 850  human
Q86SQ4    1009 gdeFCWIQd---PVIFYVTCAGYFGVMFFLNIAMFIVVMVQICGRNGkrsnrtlreEVLRNLRSVVSLTFLLGMTWGFAF 1085 human
B7ZCC9    2832 ttpFCWIKd---DHIFYISVVAYFCLIFLMNLSMFCTVLVQLTSVKSqsqk-trkkMILNDLKGTISLTFLLGLTWGFAF 2907 house mouse
Feature 1                  #   #                           
Q86Y34     495 FTPL----GLSTVYIFALFNSLQGVFICCWFTILYlPSQSTTVS 534  human
Q8IZF4     475 FSFGv--fLLPQLFLFTILNSLYGFFLFLWFCSQRcRSEAEAKA 516  human
Q50DM7     622 FSFAsgtfQLVILYLFSIITSFQGFLIFIWYWSMRlQARGGPSP 665  chimpanzee
Q8IZP9     851 FAWGp--vNVTFMYLFAIFNTLQGFFIFIFYCVAKeNVRKQWRR 892  human
Q86SQ4    1086 FAWGp--lNIPFMYLFSIFNSLQGLFIFIFHCAMKeNVQKQWRQ 1127 human
B7ZCC9    2908 FAWGp--vRIFFLYLFAICNTLQGFLIFVFYCVMKeSVREQWHM 2949 house mouse

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