brain-specific angiogenesis inhibitor 2, 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  917 AGSPSVPLVIGCAVSCMALLTLLAIYAAFWRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFL 996
Cdd:cd15988      1 TGSPSVPLMIGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  997 SSFCWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAVIV 1076
Cdd:cd15988     81 SSFCWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTASYCWLSLEGGLLYAFVGPAAVIV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1077 LVNMLIGIIVFNKLMARDGISDKSKKQRAGSERCPWASLLLPCSACGAVPSPLLSSASARNAMASLWSSCVVLPLLALTW 1156
Cdd:cd15988    161 LVNMLIGIIVFNKLMSRDGISDKSKKQRAGSEAEPCSSLLLKCSKCGVVSSAAMSSATASSAMASLWSSCVVLPLLALTW 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1370454047 1157 MSAVLAMTDRRSVLFQALFAVFNSAQGFVITAVHCFLRREVQDVVKCQMGV 1207
Cdd:cd15988    241 MSAVLAMTDRRSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVVKCQMGG 291

GPCR-Autoproteolysis INducing (GAIN) domain; The GAIN a domain of alpha-helices and beta-strands that is found in cell-adhesion GPCRs and precedes the GPS motif where the autoproteolysis occurs, family, pfam01825. The full GAIN domain, comprises the GPS and the GAIN, in cell-adhesion GPCRs, and is the functional unit for autoproteolysis. The GPS motif at the end of the GAIN domain is an ancient domain that exists in primitive ancestor organizms, and the full GAIN + GPS is conserved in all cell-adhesion GPCRs and all PKD1-related proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  602 GMSQVVRSLQELLARRTYYSGDLLFSVDILRNVTDTFKRATYVPSADDVQRFFQVVSFMVDAENKEKWDDAQQVSPGSVH 681
Cdd:pfam16489    1 GAKELARELRNATRHGPLYGGDVLTAVELLSQLFDLLATQDATLSNAFLENFVQTVSNLLDPENRESWEDLQQTERGTAA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  682 --LLRVVEDFIHLVGDALKAFQSSLIVTDNLVISIQRE--PVSAVSSDITFPMRGRRGmkdwvrHSEDRLFLPKEVLSLS 757
Cdd:pfam16489   81 tkLLRTLEEYALLLAQNMKYLTPFTIVTPNIVLSVDRLdtHNFKGARFPRFPMKGERP------KDEDSVKLPPKAFKPP 154

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1370454047   858 TDPHCASWDYSRadassGDWDTENCQTLETQAAHTRCQCQHLSTFAVLAQPPKD 911
Cdd:smart00303    1 FNPICVFWDESS-----GEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1370454047   466 WGPWNAWSLCSKTCDTGWQRRFRMC--QATGTQGYPCEGTGEEVKPCSEKRCP 516
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCcsPPPQNGGGPCTGEDVETRACNEQPCP 53

Domain present in hormone receptors;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370454047   519 HEMCRDEYVMLMTWKKAAAGEIIYNKCPPNASG-----SASRRCLLSAQgvayWGL--PSFARCISHEYRYL 583
Cdd:smart00008    2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGfsyktGASRNCTENGG----WSPpfPNYSNCTSNDYEEL 69

brain-specific angiogenesis inhibitor 2, 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  917 AGSPSVPLVIGCAVSCMALLTLLAIYAAFWRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFL 996
Cdd:cd15988      1 TGSPSVPLMIGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  997 SSFCWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAVIV 1076
Cdd:cd15988     81 SSFCWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTASYCWLSLEGGLLYAFVGPAAVIV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1077 LVNMLIGIIVFNKLMARDGISDKSKKQRAGSERCPWASLLLPCSACGAVPSPLLSSASARNAMASLWSSCVVLPLLALTW 1156
Cdd:cd15988    161 LVNMLIGIIVFNKLMSRDGISDKSKKQRAGSEAEPCSSLLLKCSKCGVVSSAAMSSATASSAMASLWSSCVVLPLLALTW 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1370454047 1157 MSAVLAMTDRRSVLFQALFAVFNSAQGFVITAVHCFLRREVQDVVKCQMGV 1207
Cdd:cd15988    241 MSAVLAMTDRRSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVVKCQMGG 291

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  917 AGSPSVPLVIGCAVSCMALLTLLAIYAAFwRFIKSERSIILLNFCLSILASNILILVGQSRVLSKG--------VCTMTA 988
Cdd:pfam00002    1 ALSLKVIYTVGYSLSLVALLLAIAIFLLF-RKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQdldhcswvGCKVVA 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  989 AFLHFFFLSSFCWVLTEAWQSYLA-VIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTrTKGYGTSSYCWLSLEGGLLYA 1067
Cdd:pfam00002   80 VFLHYFFLANFFWMLVEGLYLYTLlVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVD-PKGYGEDDGCWLSNENGLWWI 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1068 FVGPAAVIVLVNMLIGIIVFNKLMARDGISDKSKKQRagsercpwaslllpcsacgavpspllssasaRNAMASLWSSCV 1147
Cdd:pfam00002  159 IRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDL-------------------------------KQYRRLAKSTLL 207

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1370454047 1148 VLPLLALTWMSAVLAMTDRR--SVLFQALFAVFNSAQGFVI 1186
Cdd:pfam00002  208 LLPLLGITWVFGLFAFNPENtlRVVFLYLFLILNSFQGFFV 248

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1370454047   355 WEEWGSWSLCSRSCGRGSRSRMRTCV--PPQHGGKACEGPELQTKLCSMAACP 405
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCspPPQNGGGPCTGEDVETRACNEQPCP 53

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1370454047  860 PHCASWDYSraDASSGDWDTENCQTLETQAAHTRCQCQHLSTFAVL 905
Cdd:pfam01825    1 PQCVFWDFT--NSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1370454047  357 EWGSWSLCSRSCGRGSRSRMRT-CVPPQHGGKACeGPELQTKLCSMAAC 404
Cdd:pfam19028    5 EWSEWSECSVTCGGGVQTRTRTvIVEPQNGGRPC-PELLERRPCNLPPC 52

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1370454047   410 WLEWGPWGPCSTSCANGTQQRSRKCSVAGPAW--ATCTGALTDTRECSNLECP 460
Cdd:smart00209    1 WSEWSEWSPCSVTCGGGVQTRTRSCCSPPPQNggGPCTGEDVETRACNEQPCP 53

Thrombospondin type 1 domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1370454047  412 EWGPWGPCSTSCANGTQQRSRKCSVAGPAWATCTGALTDTRECSNLEC 459
Cdd:pfam00090    2 PWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49

Thrombospondin type 1 domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1370454047  467 GPWNAWSLCSKTCDTGWQRRFRMCQATGTQGYPCEGTGEEVKPCSEKRC 515
Cdd:pfam00090    1 SPWSPWSPCSVTCGKGIQVRQRTCKSPFPGGEPCTGDDIETQACKMDKC 49

sporozoite surface protein 2 (SSP2); Provisional

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370454047  347 ATCpvhGVWEEWgswSLCSRSCGRGSRSRMRtcvPPQHGGkaCEgPELQTKlCSMAACPVE 407
Cdd:PTZ00441   238 ASC---GPWDEW---TPCSVTCGKGTHSRSR---PILHEG--CT-THMVEE-CEEEECPVE 285

Hormone receptor domain; This extracellular domain contains four conserved cysteines that probably for disulphide bridges. The domain is found in a variety of hormone receptors. It may be a ligand binding domain.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370454047  519 HEMCRDEYVMLMTWKKAAAGEIIYNKCPPNAS-----GSASRRCLLSAQgvayWGLPS---FARCISH 578
Cdd:pfam02793    1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSgfdprGNASRNCTEDGT----WSEHPpsnYSNCTSN 64

brain-specific angiogenesis inhibitor 2, 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  917 AGSPSVPLVIGCAVSCMALLTLLAIYAAFWRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFL 996
Cdd:cd15988      1 TGSPSVPLMIGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  997 SSFCWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAVIV 1076
Cdd:cd15988     81 SSFCWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTASYCWLSLEGGLLYAFVGPAAVIV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1077 LVNMLIGIIVFNKLMARDGISDKSKKQRAGSERCPWASLLLPCSACGAVPSPLLSSASARNAMASLWSSCVVLPLLALTW 1156
Cdd:cd15988    161 LVNMLIGIIVFNKLMSRDGISDKSKKQRAGSEAEPCSSLLLKCSKCGVVSSAAMSSATASSAMASLWSSCVVLPLLALTW 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1370454047 1157 MSAVLAMTDRRSVLFQALFAVFNSAQGFVITAVHCFLRREVQDVVKCQMGV 1207
Cdd:cd15988    241 MSAVLAMTDRRSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVVKCQMGG 291

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  915 ELAGSPSVPLVIGCAVSCMALLTLLAIYAAFWRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFF 994
Cdd:cd15989      1 ESSGTPSVTLIVGCGLSCLALITLAVVYAALWRYIRSERSIILINFCLSIISSNILILVGQTQTHNKGICTMTTAFLHFF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  995 FLSSFCWVLTEAWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAV 1074
Cdd:cd15989     81 FLASFCWVLTEAWQSYMAVTGKIRTRLIRKRFLCLGWGLPALVVAISMGFTKAKGYGTPHYCWLSLEGGLLYAFVGPAAA 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1075 IVLVNMLIGIIVFNKLMARDGISDKSKKQRAGSERCPWASLLLPCSACGAVPSPLLSSASARNAMASLWSSCVVLPLLAL 1154
Cdd:cd15989    161 VVLVNMVIGILVFNKLVSRDGILDKKLKHRAGQMSEPHSGLTLKCAKCGVVSTTALSATTASNAMASLWSSCVVLPLLAL 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1370454047 1155 TWMSAVLAMTDRRSVLFQALFAVFNSAQGFVITAVHCFLRREVQDVVKCQM 1205
Cdd:cd15989    241 TWMSAVLAMTDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFRCRL 291

Adhesion GPCR B N-terminal region; This region is found at the N-terminus of various adhesion G-protein coupled receptor B proteins. This region contains 10 cysteine residues that probably form disulphide bonds.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047   26 SACSALASGVLYGAFSLQDLFPTIASGCSWTLENPDPTKYSLYLRFNRQEQVCAHFAPRLLPLDHYLVNFTclrpspeea 105
Cdd:pfam19188    1 DPCSTLVQGVLYGSFSLRDLFPTNASGCSWTLENPDPTKYTLYLKFTKPTQSCLPFSPRLLQFDHYLENTT--------- 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  106 vaqaESEVGRPEEEEAeaaagLELCSGSGPFTFLHFDKNFVQLCLSAEPSEAPRLLAPAALAFRFVEVLLINNNNSSQFT 185
Cdd:pfam19188   72 ----RTYLGRESFDEV-----VELCDASSPFSFLEFDKNFVQLCLLAEPRGDPESVVPGPSGDFKVEVLVINNENPSQFT 142

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1370454047  186 CGVLCRWSEECGRAA--GRACGFAQPGCSCPGEAG 218
Cdd:pfam19188  143 CGVLCRWLEECLSAStsSRPCGIMQTPCICPGTVP 177

adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G protein-coupled receptors; The B2 subfamily of class B GPCRs consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  926 IGCAVSCMALLTLLAIYAAFWRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFLSSFCWVLTE 1005
Cdd:cd15040     10 IGCGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLFGINSTDNPVLCTAVAALLHYFLLASFMWMLVE 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1006 AWQSYLAVIGRMRT--RLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAFVGPAAVIVLVNMLIG 1083
Cdd:cd15040     90 ALLLYLRLVKVFGTypRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYCWLSNGNGLYYAFLGPVLLIILVNLVIF 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1084 IIVFNKLMARDGISDKSKKQragsercpwaslllpcsacgavpspllssasarNAMASLWSSCVVLPLLALTWMSAVLAM 1163
Cdd:cd15040    170 VLVLRKLLRLSAKRNKKKRK---------------------------------KTKAQLRAAVSLFFLLGLTWIFGILAI 216

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1370454047 1164 TDRRSVlFQALFAVFNSAQGFVITAVHCFLRREVQD 1199
Cdd:cd15040    217 FGARVV-FQYLFAIFNSLQGFFIFIFHCLRNKEVRK 251

orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group V adhesion GPCRs include orphan receptors GPR133, GPR144, and closely related proteins. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the G(s) protein, leading to activation of adenylate cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, 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. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  926 IGCAVSCMALLTLLAIYAaFWRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFLSSFCWVLTE 1005
Cdd:cd15933     10 IGCGISIACLALTLIIFL-VLRVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGNKVACKVVAILLHFFFMAAFSWMLVE 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1006 AWQSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFtRTKGYGTSSYCWLSLEGGLLYAFVGPAAVIVLVNMLIGII 1085
Cdd:cd15933     89 GLHLYLMIVKVFNYKSKMRYYYFIGWGLPAIIVAISLAI-LFDDYGSPNVCWLSLDDGLIWAFVGPVIFIITVNTVILIL 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1086 VFNKLMARDGISDKSKKQRagsercpWASLllpcsacgavpspllsSASARnAMAslwsscVVLPLLALTWMSAVLAMTD 1165
Cdd:cd15933    168 VVKITVSLSTNDAKKSQGT-------LAQI----------------KSTAK-ASV------VLLPILGLTWLFGVLVVNS 217

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1370454047 1166 rRSVLFQALFAVFNSAQGFVITAVHCFLRREVQD 1199
Cdd:cd15933    218 -QTIVFQYIFVILNSLQGLMIFLFHCVLNSEVRS 250

invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors; This subgroup includes latrophilin-like proteins that are found in invertebrates such as insects and worms. Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of vertebrate latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  926 IGCAVSCMALLTLLAIYAAFwRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFLSSFCWVLTE 1005
Cdd:cd15440     10 IGCIISIVCLLLAFITFTCF-RNLQCDRNTIHKNLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFLAAFSWMLLE 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1006 AWQSYL---AVIGRMRTRlvRKRFLCLGWGLPALVVAVSVGFTRTkGYGTSSYCWLSLEGGLLYAFVGPAAVIVLVN-ML 1081
Cdd:cd15440     89 GFQLYVmlvEVFEPEKSR--IKWYYLFGYGLPALIVAVSAGVDPT-GYGTEDHCWLSTENGFIWSFVGPVIVVLLANlVF 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1082 IGIIVFnkLMARDGISDKSKKQRAGSERCPWaslllpcsacgavpspllssasarnamaslW--SSCVVLPLLALTWMSA 1159
Cdd:cd15440    166 LGMAIY--VMCRHSSRSASKKDASKLKNIRG------------------------------WlkGSIVLVVLLGLTWTFG 213

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1370454047 1160 VLAMtDRRSVLFQALFAVFNSAQGFVITAVHCFLRREVQ 1198
Cdd:cd15440    214 LLFI-NQESIVMAYIFTILNSLQGLFIFIFHCVLNEKVR 251

CD97 antigen, member of the 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. 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  926 IGCAVSCMALLtLLAIYAAFWRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFLSSFCWVLTE 1005
Cdd:cd15438     10 VGLSVSLFCLF-LCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLAAFCWMSLE 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1006 AWQSYLAVIGRMRTRLVRKRFLCL-GWGLPALVVAVSVGFTrTKGYGTSSYCWLSLEGGLLYAFVGPAAVIVLVNMLIGI 1084
Cdd:cd15438     89 GVELYLMVVQVFNTQSLKKRYLLLiGYGVPLVIVAISAAVN-SKGYGTQRHCWLSLERGFLWSFLGPVCLIILVNAIIFV 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1085 IVFNKLMAR----DGISDKSKKQRAgsercpwaslllpcsacgavpspLLSSASARnamaslwsscvvLPLLALTWMSAV 1160
Cdd:cd15438    168 ITVWKLAEKfssiNPDMEKLRKIRA-----------------------LTITAIAQ------------LCILGCTWIFGF 212

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1161 LAMTDrRSVLFQALFAVFNSAQGFVITAVHCFLRREV-QDVVKCQMGVCR 1209
Cdd:cd15438    213 FQFSD-STLVMSYLFTILNSLQGLFIFLLHCLLSKQVrEEYSRWLCAIAR 261

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  926 IGCAVS--CM--ALLTLLaiyaaFWRFIKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFLSSFCW 1001
Cdd:cd15439     10 VGLIISllCLflAILTFL-----LCRSIRNTSTSLHLQLSLCLFLADLLFLVGIDRTDNKVLCSIIAGFLHYLFLACFAW 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1002 VLTEAWQSYLAV-----IGRMRTRLVRKRFLCL-GWGLPALVVAVSVGfTRTKGYGTSSYCWLSLEGGLLYAFVGPAAVI 1075
Cdd:cd15439     85 MFLEAVHLFLTVrnlkvVNYFSSHRFKKRFMYPvGYGLPAVIVAISAA-VNPQGYGTPKHCWLSMEKGFIWSFLGPVCVI 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047 1076 VLVNMLIGIIVFNKLMARdgisdkskkqragsercpwaslllpcsacgavpsplLSS-----ASARNAMASLWSSCVVLP 1150
Cdd:cd15439    164 IVINLVLFCLTLWILREK------------------------------------LSSlnaevSTLKNTRLLTFKAIAQLF 207

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1370454047 1151 LLALTWMSAVLAMTDRRSVLfQALFAVFNSAQGFVITAVHCFLRREVQD 1199
Cdd:cd15439    208 ILGCTWILGLFQVGPVATVM-AYLFTITNSLQGVFIFLVHCLLNRQVRE 255

orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR133 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR144. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the Gs protein, leading to activation of adenylyl cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, 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. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370454047  926 IGCAVSCMALLTLLAIYAAFWRF--IKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFLSSFCWVL 1003
Cdd:cd15256     10 VGCSLSIFCLAITLVTFAVLSSVstIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLPCKIMAILLHFFFLSAFAWML 89