Conserved Protein Domain Family
7tmB2_EMR

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cd15439: 7tmB2_EMR 
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors
group II adhesion GPCRs, including the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4) and the leukocyte cell-surface antigen CD97, are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily 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 number 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 EMR2, alternative splicing results in 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. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. 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. 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: 320555
View PSSM: cd15439
Aligned: 13 rows
Threshold Bit Score: 441.78
Threshold Setting Gi: 512875582
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 290457673  599 DFSLYIISHVGIIISLVCLVLAIATFLLCRSIr-nHNTYLHLHLCVCLLLAKTLFLAGIHKTdnkmgCAIIAGFLHYLFL 677
gi 44887876   187 DPVLTVITQVGLTISLLCLFLAILTFLLCRPIq-nTSTSLHLELSLCLFLAHLLFLTGINRTepevlCSIIAGLLHFLYL 265
gi 23397681   533 DPVLTVITYMGLSVSLLCLLLAALTFLLCKAIq-nTSTSLHLQLSLCLFLAHLLFLVAIDQTghkvlCSIIAGTLHYLYL 611
gi 512875582  479 DRGLLYISRIGLGVSVLCLFLSLVTFLLCRSLr-sAHTSMLIALCGCLFLGQLIILFGLPQTqfrilCSIIAGCLHYILL 557
gi 530659080  248 RLESLLGKRLSRNRGLLCLFLAILTFLLCRSIr-nVSTSLHLQLCLCLFLADLLFLTAVTRTgsrvvCAVIAGLLHYLFL 326
gi 529432539  255 SYALLVVTYVGMSVSLVCLFLAIITFLLCRSLw-sISVTLHLHLSICLFAADLLFLVAVPHTtnqltCAITAGFLHYLFL 333
gi 558121705  725 DFPLFLISHVGLALSLLCLLLAILTFLLCRSIr-nVNTSIHLQLCLCLFVADLLFLTAVDRTrhqvgCAVIAGFLHYLFL 803
gi 557026708  108 DIALEVITYVGIILSLVCLAACIVTLKCFNSVr-tTSTTIHLHLCVCLFLAELLFLIGMDRTsnktlCGIIAGFLHYLFL 186
gi 637294160  305 SRILYIITYIGLISSVICLFLSVVTFLICHSIq-nNNTFIHIQLSMCLFLADLLFLIGIQKTdkkilCSVIAGILHYLFL 383
gi 557000448  372 DLGLTVITYIGIIISLICLFFTIFTHCCFHSIr-nPSTTLQLNLCISLFVAELIFLVGIDYTnnkiaCAIIAGILHYSFL 450
gi 586477049  826 DPVLEVITDVGLILSLLCLFLAILTFLLCRSVq--NTNTLHLNLSLCLFLANLLFLVGIDRTkpkvlCSIIAGALHYLYL 903
gi 591378062  386 DFALFVISQTGLIISLICLILAIVTFLFCHPIrntSSTFLHLQLSMCLFLADLLFIVGIDKTynklmCSITAGLLHYLFL 465
gi 602665517   90 DLILSIISYLGLSISVICLFLCIATFLFCRSSh-nSSTFIHLQLSLCLFFADLLFIAGIDKTdnkilCSVIAGMLKYLFL 168
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                 ## # #  
gi 290457673  678 ACFFWMLVEAVILFLMVRnlkvvnyfssrnIKMLHICAFGYGLPMLVVVISASVQpqgygmhnrCWLntETGFIWSFLGP 757
gi 44887876   266 ACFTWMLLEGLHLFLTVRnlkvanytstgrFKKRFMYPVGYGIPAVIIAVSAIVGpqny-gtftCWLklDKGFIWSFMGP 344
gi 23397681   612 ATLTWMLLEALYLFLTARnltvvnyssinrFMKKLMFPVGYGVPAVTVAISAASRphlygtpsrCWLqpEKGFIWGFLGP 691
gi 512875582  558 CAFCWMTLESVLLFLTVRnlnamnyltsrrSHFPTACIIGFGVPAVIVAISAAVRydgygtgksCWL--SLNLIWSFLGP 635
gi 530659080  327 ACFSWMFLEGLHLFLTVRnlkvvnytsasrFKKRFMYPFGYGFPALVVAISAAVNadgygtskhCWLslDKGFRWSFLGP 406
gi 529432539  334 ACFAWMFLEGLHLFLTIRnltvlnytsasrFRKRYIYPAGYGTPAIVVAISAAVHpggygtehyCWLsmKGGFIWSFLGP 413
gi 558121705  804 ACFAWMFLEAVVLLLTVRnlgvinyfsthsPKMWFLSLFGYGFPTLVVAVSATLMpkgysrqenCWLnmERGFIWIFLGP 883
gi 557026708  187 ACFAWMLLEGFQLYLMVRnlkvvnyfsthsIKRRFMYPIGYGLPAVIVVISAAVFhigygtknhCWLttEKGFVWSFLGP 266
gi 637294160  384 ACFVWMFLEGLNLYFIVRnlkvanyrgarkQMKISMYFCGYGLPAVIVAIAAATFpegygtrelCWLkfEKGFVWSFTGP 463
gi 557000448  451 ACFAWMCLAAVQLCLMVInlkavkffrshvIRRRYMYPVGYGAPAVIVAISAGVDhqgygtakhCWLsmERYFLWSFLGP 530
gi 586477049  904 ASFTWMFLEGLHLFLSVRnlkvakytssgrFNKKSMYLVGYGISAVIVAVSAGLNpsgygtpthCWTslQKGFIWSFIGP 983
gi 591378062  466 ACFAWMLLEAVSLYLIVRnlkvknysgtgrCTRKCMYPFGYGLPAVIVITSAASApnsygtpyhCWLnpDNGFRWNFLGP 545
gi 602665517  169 ACFVWMFLEAVNLYLIVRnlkvanysgaskYMKISMYLCGYGLPVLIVAISAGINpgafgtqyyCWL--NPDFIWSFMGP 246
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                              #  #               #   #   
gi 290457673  758 VCTVIVINSLLLTWTLWILRQRLSsvnaevstlkDTRLLTFKAFAQLFILGCSWVLGIFQIGpv----aGVMAYLFTIIN 833
gi 44887876   345 VAVIILINLVFYFQVLWILRSKLSslnkevstiqDTRVMTFKAISQLFILGCSWGLGFFMVEevgktigSIIAYSFTIIN 424
gi 23397681   692 VCAIFSVNLVLFLVTLWILKNRLSslnsevstlrNTRMLAFKATAQLFILGCTWCLGILQVGpa----aRVMAYLFTIIN 767
gi 512875582  636 VCVFITINTTLLVLTFWILRAKLAslnanvsslkNTRLLAFKALVQLFILGSTWILGFFQCGpg----aIVASYLFTICN 711
gi 530659080  407 VCAIILINITFFALTLWILRNRLSslnadvstlrDHRLLTFKAIAQLFILGCTWSLGLLQVGpa----aTVMAYLFTIVN 482
gi 529432539  414 VCVIILVNLLFFLTTLWILRDKLSslnadvtalkSTRLMTFKALAQICILGCTWGLGLLQAQgd----nIVVAFIFTIVN 489
gi 558121705  884 VCVIVGISSVIFAVTLWMLQRKLSslnsevstlkDTRLLTFKAIAQVFILGCTWIFGLFQTGpa----aVVMAYLFTILN 959
gi 557026708  267 VCTIIGINSILFVVILWILRRNLStlntdvatlkNNRSITLKAIAQCVILGCTWIVGIFHVQke----tLVLAYLFTIFN 342
gi 637294160  464 VCAIIVINLVLLCLILINLHQKFAslnkevstfrNTRALILKALAHVFILGVSWCLGLFLYGpl----aTVMAYLFTITN 539
gi 557000448  531 VCLIILVNLTLFIVIIWILKEKLAsldkdvstvkESRSLTFKVMAQFLILGCTWMFGLFHVGqg----tLIMAYVFTILN 606
gi 586477049  984 VCVVVVINLIFYLTTLWILRDRLSslnkevskmkNTRMLTFKAIAQLFLLGCXWSLGFFLAEsvkesfrSVIAYAFTITN 1063
gi 591378062  546 VCAVVVINFVFFCLTLKLLREHLSslnaelstlrNTRSLTFKALAHLLVLGLTWGLGTFQFGpl----aTVMGYLFTITN 621
gi 602665517  247 VCALIVVNLVLFCLILKNLHEKLAslnseissvrNTRSLIFKAIAHVFILGVTWCFGLFQYGll----dEFMAYLFTITS 322
                         250       260
                  ....*....|....*....|....*...
Feature 1                                     
gi 290457673  834 SLQGAFIFLIHCLLNGQVREEYKRWITG 861
gi 44887876   425 TLQGVLLFVVHCLLNRQVRLIILSVISL 452
gi 23397681   768 SLQGVFIFLVYCLLSQQVREQYGKWSKG 795
gi 512875582  712 SLQGAFIFLVHCLLNHQVREEYRKVFHR 739
gi 530659080  483 SLQGAFIFLVHCLLNRQVREEYRRWIKG 510
gi 529432539  490 SLQGAFIFLVHCVLNRQVTEQYRRWFRV 517
gi 558121705  960 SLQGVFIFLVHCLLNRQVQEEYKRWFTC 987
gi 557026708  343 SLQGTAIFTIHCVLNRQVREEYRKYLKG 370
gi 637294160  540 SVQGVFIFLVHCLFNKKVRETYLRWICC 567
gi 557000448  607 SFQGLFIFLVYCVLNRQGTSTSASTPVQ 634
gi 586477049 1064 VLQGVYIYGVHCLLNRQVREEYKRWLTR 1091
gi 591378062  622 SMLGTFIFVVHCLLNRKVREEYWKLFTR 649
gi 602665517  323 SVQGVFIFLVHCLLNQKVREAYWRWICC 350

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