Conserved Protein Domain Family
7tmB2_BAI3

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cd15989: 7tmB2_BAI3 
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 family of seven-transmembrane G protein-coupled receptors
Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all 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. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediates direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.
Statistics
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PSSM-Id: 320655
View PSSM: cd15989
Aligned: 4 rows
Threshold Bit Score: 533.108
Threshold Setting Gi: 141796897
Created: 25-Jun-2014
Updated: 18-Aug-2016
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 311033353  872 ESSGTPSVTLIVGSGLSCLALITLAVVYAALWRYIRSERSIILINFCLSIISSNILILVGQTQTHNKSICTTTTAFLHFF 951
gi 512841635  871 ESSGTPSVTLIIGCGLSCLALITLAVVYAALWRYIKSERSIILINFCLSIISSNILILVGQTQIHNKGICTMTTAFLHFF 950
gi 141796897    2 EYSGVPSVTLIVGCGLSCLALITLAVVYAVLWRYIRSERSIILINFCLSIICSNILILVGQTQTHNAGICTMTTAFLHFF 81
gi 449283602  605 ESSGTPSVTLIVGSGLSCLALITLAVVYAALWRYIRSERSIILINFCLSIISSNILILVGQTQTHNKGICTTTTAFLHFF 684
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                              ## # #     
gi 311033353  952 FLASFCWVLTEAWQSYMAVTGKIRTRLIRKRFLCLGWGLPALVVATSVGFTRTKGYGTdHYCWLSLEGGLLYAFVGPAAA 1031
gi 512841635  951 FLASFCWVLTEAWQSYMAVTGKIRTRVIRKRFLCLGWGLPALVVAISMGFTKAKGYGTpHYCWLSLEGGLLYAFVGPAAA 1030
gi 141796897   82 FLASFCWVLTEAWQSYMAVTGKVRTRLIRKRFLCLGWGLPALVVAISMGFTKAKGYGTpQYCWLSLEGGLLYAFVGPAAA 161
gi 449283602  685 FLASFCWVLTEAWQSYMAVTGKIRTRLIRKRFLCLGWGLPALVVAISIGFTKTKGYGTaHYCWLSLEGGLLYAFVGPAAA 764
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 311033353 1032 VVLVNMVIGILVFNKLVSRDGILDKKLKHRAGQMSEPHSGLTLKCAKCGVVSTTALSATTASNAMASLWSSCVVLPLLAL 1111
gi 512841635 1031 VVLVNMVIGILVFNKLVSRDGILDKKLKHRAGQMSEPHSGLTLKCAKCGVVSTTALSATTASNAMASLWSSCVVLPLLAL 1110
gi 141796897  162 VVLVNMVIGILVFNKLVSRDGILDKKLKHRAGQMSEPHTGLTLKCAKCGVVSTTALSATTASNAMASLWSSCVVLPLLAL 241
gi 449283602  765 VVLVNMVIGILVFNKLVSRDGILDKKLKHRAGQMSEPHSGLTLKCAKCGVVSTTALSATTASNAMASLWSSCVVLPLLAL 844
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
Feature 1          #  #            #   #                               
gi 311033353 1112 TWMSAVLAMTDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFRCRLRN 1164
gi 512841635 1111 TWMSAVLAMTDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFRCRLRN 1163
gi 141796897  242 TWMSAVLAMTDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFRCRLRN 294
gi 449283602  845 TWMSAVLAMTDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFRCRLRN 897

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