Conserved Protein Domain Family
7tmB2_EMR_Adhesion_II

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cd15931: 7tmB2_EMR_Adhesion_II 
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors
group II adhesion GPCRs, including the leukocyte cell-surface antigen CD97 and the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4), are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily B2 of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying numbers of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of CD97, alternative splicing results in three isoforms possessing either three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. On the other hand, EMR2 generates four isoforms possessing either two (EGF1,2), three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, 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. For example, CD97, which is involved in angiogenesis and the migration and invasion of tumor cells, has been shown to promote cell aggregation in a GPS proteolysis-dependent manner. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.
Statistics
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PSSM-Id: 320597
View PSSM: cd15931
Aligned: 3 rows
Threshold Bit Score: 373.003
Threshold Setting Gi: 47214911
Created: 5-Feb-2015
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 90110013  544 DWKLTLITRVGLALSLFCLLLCILTFLLVRPIqgSRTTIHLHLCICLFVGSTIFLAGIENEggqvglrCRLVAGLLHYCF 623
gi 290457673 599 DFSLYIISHVGIIISLVCLVLAIATFLLCRSIrnHNTYLHLHLCVCLLLAKTLFLAGIHKTdnk--mgCAIIAGFLHYLF 676
gi 47214911   44 NPFLEWLNRVCVIVGLFFFGLAIFTFLLCSWNpkINNTARLHLCLNLSMSHLLLLWNEEYVene--laCTVMAGLLHFLV 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                   ## # 
gi 90110013  624 LAAFCWMSLEGLELYFLVVrvfq-----gqgLSTRWLCLIGYGVPLLIVGVSAAIYskgyg--rpryCWLdfEQGFLWSF 696
gi 290457673 677 LACFFWMLVEAVILFLMVRnlkvvnyfssrnIKMLHICAFGYGLPMLVVVISASVQpqgyg--mhnrCWLntETGFIWSF 754
gi 47214911  122 IASFVWMLLEALQLHLLVRrltkvqviqrdgLPRPLLYLIGYGVPFTIVGVSALVYsdgygateakmCWLsqTRHFNWAL 201
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #                                                       #  #           #   #    
gi 90110013  697 LGPVTFIILCNAVIFVTTVWKLTQKFSeinpdmkklkKARALTITAIAQLFLLGCTWVFGLFIFDdrsLVLTYVFTILNC 776
gi 290457673 755 LGPVCTVIVINSLLLTWTLWILRQRLSsvnaevstlkDTRLLTFKAFAQLFILGCSWVLGIFQIGpvaGVMAYLFTIINS 834
gi 47214911  202 TGPVIAILGINWILFCATLWCLRPTLAnmrsdisqskDTRLILFKIVAQFVILGCTWILGLYQTN---LFFQVLFIILNS 278
                        250       260
                 ....*....|....*....|....*.
Feature 1                                  
gi 90110013  777 LQGAFLYLLHCLLNKKVREEYRKWAC 802
gi 290457673 835 LQGAFIFLIHCLLNGQVREEYKRWIT 860
gi 47214911  279 QQGTFLFIVHCLLNKEVRDEYIKWLT 304

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