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Conserved domains on  [gi|229093087|ref|NP_740746|]
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adhesion G protein-coupled receptor G3 isoform 1 precursor [Homo sapiens]

Protein Classification

adhesion G protein-coupled receptor( domain architecture ID 12027400)

adhesion G protein-coupled receptor (GPCR) is involved in cell adhesion and cell-cell interactions; GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins by binding to an extracellular agonist, which induces conformational changes that lead to the activation of heterotrimeric G proteins, which then bind to and activate numerous downstream effector proteins

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
265-527 2.24e-154

orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR97 is an orphan receptor that has been classified into the group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR112, GPR114, and GPR126. 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. 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.


:

Pssm-ID: 320558 [Multi-domain]  Cd Length: 277  Bit Score: 442.32  E-value: 2.24e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 265 VHILTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAV 344
Cdd:cd15442    1 AQTLVTISSAGCGVSMVFLIFTIILYFFLRFTYQKFKSEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKALGGV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 345 FHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSANSYGLYTIRDRENRTSLELCWFRE 424
Cdd:cd15442   81 THYFLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLCLVGWGFPALVVTITGSINSYGAYTIMDMANRTTLHLCWINS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 425 GtTMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPL--GLST 502
Cdd:cd15442  161 K-HLTVHYITVCGYFGLTFLFNTVVLGLVAWKIFHLQSATAGKEKCQAWKGGLTVLGLSCLLGVTWGLAFFTYGsmSVPT 239
                        250       260
                 ....*....|....*....|....*
gi 229093087 503 VYIFALFNSLQGVFICCWFTILYLP 527
Cdd:cd15442  240 VYIFALLNSLQGLFIFIWFVILYYP 264
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
214-255 5.65e-15

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.


:

Pssm-ID: 460350  Cd Length: 44  Bit Score: 68.87  E-value: 5.65e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 229093087  214 TCVFWDVTKGTTGDWSSEGCSTEVRPEG-TVCCCDHLTFFALL 255
Cdd:pfam01825   2 QCVFWDFTNSTTGRWSTEGCTTVSLNDThTVCSCNHLTSFAVL 44
 
Name Accession Description Interval E-value
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
265-527 2.24e-154

orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR97 is an orphan receptor that has been classified into the group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR112, GPR114, and GPR126. 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. 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.


Pssm-ID: 320558 [Multi-domain]  Cd Length: 277  Bit Score: 442.32  E-value: 2.24e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 265 VHILTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAV 344
Cdd:cd15442    1 AQTLVTISSAGCGVSMVFLIFTIILYFFLRFTYQKFKSEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKALGGV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 345 FHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSANSYGLYTIRDRENRTSLELCWFRE 424
Cdd:cd15442   81 THYFLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLCLVGWGFPALVVTITGSINSYGAYTIMDMANRTTLHLCWINS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 425 GtTMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPL--GLST 502
Cdd:cd15442  161 K-HLTVHYITVCGYFGLTFLFNTVVLGLVAWKIFHLQSATAGKEKCQAWKGGLTVLGLSCLLGVTWGLAFFTYGsmSVPT 239
                        250       260
                 ....*....|....*....|....*
gi 229093087 503 VYIFALFNSLQGVFICCWFTILYLP 527
Cdd:cd15442  240 VYIFALLNSLQGLFIFIWFVILYYP 264
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
268-517 2.56e-34

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.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 130.09  E-value: 2.56e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087  268 LTRISQAGCGVSMIFLAFTIILYAFLR-LSRERfksedaPKIHVALGGSLFLLNLAFLV------NVGSGSKGSDAACWA 340
Cdd:pfam00002   4 LKVIYTVGYSLSLVALLLAIAIFLLFRkLHCTR------NYIHLNLFASFILRALLFLVgdavlfNKQDLDHCSWVGCKV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087  341 RGAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGhYFLKLSLVGWGLPALMVIGTGSANSYGLYTIrdrenrtslELC 420
Cdd:pfam00002  78 VAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERK-YFWWYLLIGWGVPALVVGIWAGVDPKGYGED---------DGC 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087  421 WFRegtTMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRAT--AVKERGKNRKKVLTLLGLSSLVGVTWGLAIF--- 495
Cdd:pfam00002 148 WLS---NENGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETnmGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFafn 224
                         250       260
                  ....*....|....*....|....
gi 229093087  496 --TPLGLSTVYIFALFNSLQGVFI 517
Cdd:pfam00002 225 peNTLRVVFLYLFLILNSFQGFFV 248
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
214-255 5.65e-15

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.


Pssm-ID: 460350  Cd Length: 44  Bit Score: 68.87  E-value: 5.65e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 229093087  214 TCVFWDVTKGTTGDWSSEGCSTEVRPEG-TVCCCDHLTFFALL 255
Cdd:pfam01825   2 QCVFWDFTNSTTGRWSTEGCTTVSLNDThTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
212-256 6.24e-09

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


Pssm-ID: 197639  Cd Length: 49  Bit Score: 52.00  E-value: 6.24e-09
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 229093087   212 TLTCVFWDvtkGTTGDWSSEGCSTEVRPEG-TVCCCDHLTFFALLL 256
Cdd:smart00303   2 NPICVFWD---ESSGEWSTRGCELLETNGThTTCSCNHLTTFAVLM 44
 
Name Accession Description Interval E-value
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
265-527 2.24e-154

orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR97 is an orphan receptor that has been classified into the group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR112, GPR114, and GPR126. 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. 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.


Pssm-ID: 320558 [Multi-domain]  Cd Length: 277  Bit Score: 442.32  E-value: 2.24e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 265 VHILTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAV 344
Cdd:cd15442    1 AQTLVTISSAGCGVSMVFLIFTIILYFFLRFTYQKFKSEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKALGGV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 345 FHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSANSYGLYTIRDRENRTSLELCWFRE 424
Cdd:cd15442   81 THYFLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLCLVGWGFPALVVTITGSINSYGAYTIMDMANRTTLHLCWINS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 425 GtTMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPL--GLST 502
Cdd:cd15442  161 K-HLTVHYITVCGYFGLTFLFNTVVLGLVAWKIFHLQSATAGKEKCQAWKGGLTVLGLSCLLGVTWGLAFFTYGsmSVPT 239
                        250       260
                 ....*....|....*....|....*
gi 229093087 503 VYIFALFNSLQGVFICCWFTILYLP 527
Cdd:cd15442  240 VYIFALLNSLQGLFIFIWFVILYYP 264
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
265-527 2.33e-127

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 over-expressed 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.


Pssm-ID: 320386 [Multi-domain]  Cd Length: 267  Bit Score: 373.29  E-value: 2.33e-127
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 265 VHILTRISQAGCGVSMIFLAFTIILYAFLRLSRErfksEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAV 344
Cdd:cd15258    1 LHILTFISYVGCGISAIFLAITILTYIAFRKLRR----DYPSKIHMNLCAALLLLNLAFLLSSWIASFGSDGLCIAVAVA 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 345 FHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSANSYGLYTIRD--RENRTSLELCWF 422
Cdd:cd15258   77 LHYFLLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPITIpnGEGFQNDSFCWI 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 423 REgttMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFT--PLGL 500
Cdd:cd15258  157 RD---PVVFYITVVGYFGLTFLFNMVMLATVLVQICRLREKAQATPRKRALHDLLTLLGLTFLLGLTWGLAFFAwgPFNL 233
                        250       260
                 ....*....|....*....|....*..
gi 229093087 501 STVYIFALFNSLQGVFICCWFTILYLP 527
Cdd:cd15258  234 PFLYLFAIFNSLQGFFIFIWYCSMKEN 260
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
266-525 2.76e-73

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.


Pssm-ID: 320168 [Multi-domain]  Cd Length: 253  Bit Score: 233.62  E-value: 2.76e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 266 HILTRISQAGCGVSMIFLAFTIILYAFLRLSRERFksedAPKIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVF 345
Cdd:cd15040    2 KALSIITYIGCGLSLLGLLLTIITYILFRKLRKRK----PTKILLNLCLALLLANLLFLF--GINSTDNPVLCTAVAALL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 346 HYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSANSYGLYtirdrenrTSLELCWFReg 425
Cdd:cd15040   76 HYFLLASFMWMLVEALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYG--------NSSGYCWLS-- 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 426 tTMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPLGLSTV-- 503
Cdd:cd15040  146 -NGNGLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQLRAAVSLFFLLGLTWIFGILAIFGARVVfq 224
                        250       260
                 ....*....|....*....|..
gi 229093087 504 YIFALFNSLQGVFICCWFTILY 525
Cdd:cd15040  225 YLFAIFNSLQGFFIFIFHCLRN 246
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
267-524 2.56e-59

class B family of seven-transmembrane G protein-coupled receptors; The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 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. 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. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.


Pssm-ID: 410627 [Multi-domain]  Cd Length: 260  Bit Score: 197.43  E-value: 2.56e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRLSRERfksedAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVFH 346
Cdd:cd13952    3 ALSIITYIGCSLSLVGLLLTIITYLLFPKLRNL-----RGKILINLCLSLLLAQLLFLIGQLLTSSDRPVLCKALAILLH 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSANSYGLYTIRDRENrtslELCWFregT 426
Cdd:cd13952   78 YFLLASFFWMLVEAFDLYRTFVKVFGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYGG----EYCWL---S 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 427 TMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATA-VKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPLGLSTV-- 503
Cdd:cd13952  151 NGNALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPkQSERKSDRKQLRAYLKLFPLMGLTWIFGILAPFVGGSLvf 230
                        250       260
                 ....*....|....*....|..
gi 229093087 504 -YIFALFNSLQGVFICCWFTIL 524
Cdd:cd13952  231 wYLFDILNSLQGFFIFLIFCLK 252
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
268-521 2.24e-56

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR114 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR97, GPR112, and GPR126. 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.


Pssm-ID: 320559 [Multi-domain]  Cd Length: 268  Bit Score: 189.97  E-value: 2.24e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLRlsreRFKSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVFHY 347
Cdd:cd15443    4 LTYISIVGCSISAAASLLTILLHFFSR----KQPKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQSTWLCRAAAALLHY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 348 FLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSA--NSYGLYTIRDRENRTSLELCWFREG 425
Cdd:cd15443   80 SLLCCLTWMAIEGFHLYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFkrEAYGPHTIPTGTGYQNASMCWITSS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 426 TTMYALyitVHGYFLITFLFGMVVLALVVWKIFTLsRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFT--PLGLSTV 503
Cdd:cd15443  160 KVHYVL---VLGYAGLTSLFNLVVLAWVVRMLRRL-RSRKQELGERARRDWVTVLGLTCLLGTTWALAFFSfgVFLIPQL 235
                        250
                 ....*....|....*...
gi 229093087 504 YIFALFNSLQGVFICCWF 521
Cdd:cd15443  236 FLFTIINSLYGFFICLWY 253
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
267-517 5.28e-54

Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR112 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR64, GPR97, GPR114, and GPR126. GPR112 is specifically expressed in normal enterochromatin cells and gastrointestinal neuroendocrine carcinoma cells, but its biological function is unknown. 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.


Pssm-ID: 320663  Cd Length: 269  Bit Score: 183.71  E-value: 5.28e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYaflrLSRERFKSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVFH 346
Cdd:cd15997    3 ILTLITYLGCGISSIFLGITLVTY----LAFEKLRRDYPSKILINLCTALLMLNLVFLLNSWLSSFNNYGLCITVAAFLH 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSAN--SYGLYTIRDRENRTSLeLCWFRE 424
Cdd:cd15997   79 YFLLASFTWMGLEAVHMYFALVKVFNIYIPNYILKFCIAGWGIPAVVVALVLAINkdFYGNELSSDSLHPSTP-FCWIQD 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 425 GTtmyALYITVHGYFLITFLFGMVVLALVVWKIftlsRATAVKERGKNRKKVL-----TLLGLSSLVGVTWGLAIFT--P 497
Cdd:cd15997  158 DV---VFYISVVAYFCLIFLCNISMFITVLIQI----RSMKAKKPSRNWKQGFlhdlkSVASLTFLLGLTWGFAFFAwgP 230
                        250       260
                 ....*....|....*....|
gi 229093087 498 LGLSTVYIFALFNSLQGVFI 517
Cdd:cd15997  231 VRIFFLYLFSICNTLQGFFI 250
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
267-517 1.48e-50

orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B secretin-like receptors of seven-transmembrane G protein-coupled receptors; GPR64 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR97, GPR112, GPR114, and GPR126. 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 over-expressed 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. 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.


Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 174.63  E-value: 1.48e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYaflrLSRERFKSEDAPKIHVALGGSLFLLNLAFLVNVGSG-SKGSDAACWARGAVF 345
Cdd:cd15444    3 ILTFITYIGCGLSAIFLSVTLVTY----IAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIAlYKDIVGLCISVAVFL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 346 HYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMV--IGTGSANSYGLYTIRDRENRTSLELCWFR 423
Cdd:cd15444   79 HYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVaiVLAVSKDNYGLGSYGKSPNGSTDDFCWIN 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 424 EGTtmyALYITVHGYFLITFLFGMVVLALVvwkIFTLSRATAVKERGKNRKKVL----TLLGLSSLVGVTWGLAIFT--P 497
Cdd:cd15444  159 NNI---VFYITVVGYFCVIFLLNISMFIVV---LVQLCRIKKQKQLGAQRKTSLqdlrSVAGITFLLGITWGFAFFAwgP 232
                        250       260
                 ....*....|....*....|
gi 229093087 498 LGLSTVYIFALFNSLQGVFI 517
Cdd:cd15444  233 VNLAFMYLFAIFNTLQGFFI 252
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
266-521 7.39e-48

orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR56 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as 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. 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.


Pssm-ID: 320661  Cd Length: 269  Bit Score: 167.31  E-value: 7.39e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 266 HILTRISQAGCGVSMIFLAFTIILYaflrLSRERFKSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVF 345
Cdd:cd15995    2 HYLTILTYVGCIISALASVFTIAFY----LCSRRKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGGMFL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 346 HYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMV--IGTGSANSYGLYTI---RDRENRTSLELC 420
Cdd:cd15995   78 HFSLLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVtlIFLVDQDNYGPIILavhRSPEKVTYATIC 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 421 WFREGTTMyalYITVHGYFLITFLFGMVVLALVVWKIFTLsratavKERGKNRKKVLTLLGLSSLVGVTWGLAIFT---- 496
Cdd:cd15995  158 WITDSLIS---NITNLGLFSLVFLFNMAMLATMVVEILRL------RPRTHKWSHVLTLLGLSLVLGIPWALAFFSfasg 228
                        250       260
                 ....*....|....*....|....*
gi 229093087 497 PLGLSTVYIFALFNSLQGVFICCWF 521
Cdd:cd15995  229 TFQLVIVYLFTIINSLQGFLIFLWY 253
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
267-517 5.58e-45

orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR126 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR64, GPR97, GPR112, and GPR114. GPR126 is required in Schwann cells for proper differentiation and myelination via G-Protein Activation. GPR126 is believed to couple to G(s)-protein, which leads to activation of adenylate cyclase for cAMP production. 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.


Pssm-ID: 320662  Cd Length: 271  Bit Score: 159.67  E-value: 5.58e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILY-AFLRLSRerfkseDAP-KIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAV 344
Cdd:cd15996    3 VLTFITYIGCGISAIFSAATLLTYiAFEKLRR------DYPsKILMNLSTALLFLNLVFLLDGWIASFEIDELCITVAVL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 345 FHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPAL---MVIGTGSANSYGLYTIRDRENRTSLELCW 421
Cdd:cd15996   77 LHFFLLATFTWMGLEAIHMYIALVKVFNTYIRRYILKFCIIGWGLPALivsIVLASTNDNYGYGYYGKDKDGQGGDEFCW 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 422 FREGTTmyaLYITVHGYFLITFLFGMVVLALVVWKIF----TLSRATAVKERGKNRKKVLTllgLSSLVGVTWGLAIFT- 496
Cdd:cd15996  157 IKNPVV---FYVTCAAYFGIMFLMNVAMFIVVMVQICgrngKRSNRTLREEILRNLRSVVS---LTFLLGMTWGFAFFAw 230
                        250       260
                 ....*....|....*....|..
gi 229093087 497 -PLGLSTVYIFALFNSLQGVFI 517
Cdd:cd15996  231 gPVNLAFMYLFTIFNSLQGLFI 252
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
267-517 9.35e-35

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.


Pssm-ID: 320599 [Multi-domain]  Cd Length: 252  Bit Score: 131.30  E-value: 9.35e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRLSR-ERFKsedapkIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVF 345
Cdd:cd15933    3 ALSIISYIGCGISIACLALTLIIFLVLRVLSsDRFQ------IHKNLCVALLLAQILLLA--GEWAEGNKVACKVVAILL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 346 HYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGH--YFlklsLVGWGLPALMVIGTGSAN--SYGLYTIrdrenrtslelCW 421
Cdd:cd15933   75 HFFFMAAFSWMLVEGLHLYLMIVKVFNYKSKMryYY----FIGWGLPAIIVAISLAILfdDYGSPNV-----------CW 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 422 FREGTTMYALYItvhGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNR------KKVLTLLglsSLVGVTWGLAIF 495
Cdd:cd15933  140 LSLDDGLIWAFV---GPVIFIITVNTVILILVVKITVSLSTNDAKKSQGTLAqikstaKASVVLL---PILGLTWLFGVL 213
                        250       260
                 ....*....|....*....|....
gi 229093087 496 TPLGLSTV--YIFALFNSLQGVFI 517
Cdd:cd15933  214 VVNSQTIVfqYIFVILNSLQGLMI 237
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
268-517 2.56e-34

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.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 130.09  E-value: 2.56e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087  268 LTRISQAGCGVSMIFLAFTIILYAFLR-LSRERfksedaPKIHVALGGSLFLLNLAFLV------NVGSGSKGSDAACWA 340
Cdd:pfam00002   4 LKVIYTVGYSLSLVALLLAIAIFLLFRkLHCTR------NYIHLNLFASFILRALLFLVgdavlfNKQDLDHCSWVGCKV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087  341 RGAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGhYFLKLSLVGWGLPALMVIGTGSANSYGLYTIrdrenrtslELC 420
Cdd:pfam00002  78 VAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERK-YFWWYLLIGWGVPALVVGIWAGVDPKGYGED---------DGC 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087  421 WFRegtTMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRAT--AVKERGKNRKKVLTLLGLSSLVGVTWGLAIF--- 495
Cdd:pfam00002 148 WLS---NENGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETnmGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFafn 224
                         250       260
                  ....*....|....*....|....
gi 229093087  496 --TPLGLSTVYIFALFNSLQGVFI 517
Cdd:pfam00002 225 peNTLRVVFLYLFLILNSFQGFFV 248
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
267-518 3.90e-27

Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G protein-coupled receptors; The subfamily B3 of class B GPCRs consists of Methuselah (Mth) and its closely related proteins found in bilateria. Mth was originally identified in Drosophila as a GPCR affecting stress resistance and aging. In addition to the seven transmembrane helices, Mth contains an N-terminal extracellular domain involved in ligand binding, and a third intracellular loop (IC3) required for the specificity of G-protein coupling. Drosophila Mth mutants showed an increase in average lifespan by 35% and greater resistance to a variety of stress factors, including starvation, high temperature, and paraquat-induced oxidative toxicity. Moreover, mutations in two endogenous peptide ligands of Methuselah, Stunted A and B, showed an increased in lifespan and resistance to oxidative stress induced by dietary paraquat. These results strongly suggest that the Stunted-Methuselah system plays important roles in stress response and aging.


Pssm-ID: 410632 [Multi-domain]  Cd Length: 270  Bit Score: 110.39  E-value: 3.90e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRLSRerfksedapKIH----VALGGSLFLLNLAFLVNVGSGSkGSDAACWARG 342
Cdd:cd15039    3 ILGILTLIGLIISLVFLLLTLAVYALLPELR---------NLHgkclMCLVLSLFVAYLLLLIGQLLSS-GDSTLCVALG 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 343 AVFHYFLLCAFTWMGLEAFHLYL----LAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSAN----------SYGLYTi 408
Cdd:cd15039   73 ILLHFFFLAAFFWLNVMSFDIWRtfrgKRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDfspntdslrpGYGEGS- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 409 rdrenrtslelCWFREGttmYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAV--KERGKNRKKVLTLLGLSSLV 486
Cdd:cd15039  152 -----------CWISNP---WALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKvqSRLRSDKQRFRLYLKLFVIM 217
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 229093087 487 GVTWGLAIFTPL-GLSTV--YIFALFNSLQGVFIC 518
Cdd:cd15039  218 GVTWILEIISWFvGGSSVlwYIFDILNGLQGVFIF 252
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
268-517 6.63e-26

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.


Pssm-ID: 320556 [Multi-domain]  Cd Length: 259  Bit Score: 106.58  E-value: 6.63e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLR-LSRERFKsedapkIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFH 346
Cdd:cd15440    4 LTFITYIGCIISIVCLLLAFITFTCFRnLQCDRNT------IHKNLCLCLLIAEIVFLL--GIDQTENRTLCGVIAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLsLVGWGLPALMVIGTGSANSYGLYTIRdrenrtsleLCWFRegT 426
Cdd:cd15440   76 YFFLAAFSWMLLEGFQLYVMLVEVFEPEKSRIKWYY-LFGYGLPALIVAVSAGVDPTGYGTED---------HCWLS--T 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 427 TMYALYITVhGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLT----LLGLSSLVGVTWGLAIFTPLGLST 502
Cdd:cd15440  144 ENGFIWSFV-GPVIVVLLANLVFLGMAIYVMCRHSSRSASKKDASKLKNIRGwlkgSIVLVVLLGLTWTFGLLFINQESI 222
                        250
                 ....*....|....*..
gi 229093087 503 V--YIFALFNSLQGVFI 517
Cdd:cd15440  223 VmaYIFTILNSLQGLFI 239
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
268-517 1.45e-22

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.


Pssm-ID: 320554 [Multi-domain]  Cd Length: 261  Bit Score: 97.14  E-value: 1.45e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSedapkIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFHY 347
Cdd:cd15438    4 LTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNT-----IHLHLCLSLFLAHLIFLL--GINNTNNQVACAVVAGLLHY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 348 FLLCAFTWMGLEAFHLYLLAVRVFNTY-FGHYFlkLSLVGWGLPALMVIGTGSANSYGLYTIRDrenrtslelCWF-REG 425
Cdd:cd15438   77 FFLAAFCWMSLEGVELYLMVVQVFNTQsLKKRY--LLLIGYGVPLVIVAISAAVNSKGYGTQRH---------CWLsLER 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 426 TTMYALYitvhGYFLITFLFGMVVLALVVWKIfTLSRATAVKERGKNRK-KVLTLLGLSSL--VGVTW--GLAIFTPLGL 500
Cdd:cd15438  146 GFLWSFL----GPVCLIILVNAIIFVITVWKL-AEKFSSINPDMEKLRKiRALTITAIAQLciLGCTWifGFFQFSDSTL 220
                        250
                 ....*....|....*..
gi 229093087 501 STVYIFALFNSLQGVFI 517
Cdd:cd15438  221 VMSYLFTILNSLQGLFI 237
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
267-517 3.15e-22

Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; Group I adhesion GPCRs consist of latrophilins (also called lectomedins or latrotoxin receptors) and 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 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.


Pssm-ID: 320380 [Multi-domain]  Cd Length: 257  Bit Score: 96.04  E-value: 3.15e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRlsreRFKSeDAPKIHVALGGSLFLLNLAFLVNVGSGSkgSDAACWARGAVFH 346
Cdd:cd15252    3 ILTRITQVGIIISLVCLAICIFTFWFFR----GLQS-DRTTIHKNLCISLFLAELVFLIGINTTT--NKIFCSVIAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLAVRVFntYFGHYFLK-LSLVGWGLPALmVIGTGSANSYGLYtirdrenrTSLELCWFReg 425
Cdd:cd15252   76 YFFLAAFAWMFIEGIQLYLMLVEVF--ENEGSRHKnFYIFGYGSPAV-IVGVSAALGYRYY--------GTTKVCWLS-- 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 426 TTMYALYITVHGYFLItFLFGMVVLALVVWKIFTLSrATAVKERG---KNRKKVLTLLGLSSLVGVTW--GLAIFTPLGL 500
Cdd:cd15252  143 TENYFIWSFIGPATLI-ILLNLIFLGVAIYKMFRHT-AGLKPEVScleNIRSWARGAIALLFLLGLTWifGVLHINHASV 220
                        250
                 ....*....|....*..
gi 229093087 501 STVYIFALFNSLQGVFI 517
Cdd:cd15252  221 VMAYLFTVSNSLQGMFI 237
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
268-522 8.14e-22

orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR128 is an orphan receptor of the adhesion family (subclass B2) that belongs to the class B GPCRs. Expression of GPR128 was detected in the mouse intestinal mucosa and is thought to be involved in energy balance, as its knockout mice showed a decrease in body weight gain and an increase in intestinal contraction frequency compared to wild-type controls. 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. 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.


Pssm-ID: 320385 [Multi-domain]  Cd Length: 303  Bit Score: 96.10  E-value: 8.14e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLRLSRerfKSEDApKIHVALGGSLFLLNLAFLVNVGSGSK--------------- 332
Cdd:cd15257    4 LDIISTIGCVLSIAGLVITIIFHLHTRKLR---KSSVT-WVLLNLCSSLLLFNIIFTSGVENTNNdyeistvpdretntv 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 333 --------GSDAACWARGAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMV-IGTGSANSY 403
Cdd:cd15257   80 llseeyvePDTDVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQASAIGWGIPAVVVaITLGATYRF 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 404 GLYTIRDRENRTSLELCWFR--------EGTTMYALYITVHgyflITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKK 475
Cdd:cd15257  160 PTSLPVFTRTYRQEEFCWLAaldknfdiKKPLLWGFLLPVG----LILITNVILFIMTSQKVLKKNNKKLTTKKRSYMKK 235
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 229093087 476 VLTLLGLSSLVGVTWGLAIFTPLG-----LSTVYIFALFNSLQGVFICCWFT 522
Cdd:cd15257  236 IYITVSVAVVFGITWILGYLMLVNndlskLVFSYIFCITNTTQGVQIFILYT 287
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
267-517 3.39e-21

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.


Pssm-ID: 320555 [Multi-domain]  Cd Length: 263  Bit Score: 93.17  E-value: 3.39e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSedapkIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFH 346
Cdd:cd15439    3 ALTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTS-----LHLQLSLCLFLADLLFLV--GIDRTDNKVLCSIIAGFLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLA--VRVFNTYFGHYFLKLS--LVGWGLPALMVIGTGSANSYGLYTirdrenrtsLELCWF 422
Cdd:cd15439   76 YLFLACFAWMFLEAVHLFLTVrnLKVVNYFSSHRFKKRFmyPVGYGLPAVIVAISAAVNPQGYGT---------PKHCWL 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 423 R-EGTTMYALYITVHGYFLITFLFGMVVLALVVWKIFTL-SRATAVKErgknrKKVLTLLGLSSLV--GVTWGLAIFT-- 496
Cdd:cd15439  147 SmEKGFIWSFLGPVCVIIVINLVLFCLTLWILREKLSSLnAEVSTLKN-----TRLLTFKAIAQLFilGCTWILGLFQvg 221
                        250       260
                 ....*....|....*....|.
gi 229093087 497 PLGLSTVYIFALFNSLQGVFI 517
Cdd:cd15439  222 PVATVMAYLFTITNSLQGVFI 242
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
267-517 9.51e-21

Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled receptors; 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 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.


Pssm-ID: 320673 [Multi-domain]  Cd Length: 258  Bit Score: 91.91  E-value: 9.51e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRLSRErfkseDAPKIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFH 346
Cdd:cd16007    3 LLSVITWVGIVISLVCLAICISTFCFLRGLQT-----DRNTIHKNLCINLFLAELLFLI--GIDKTQYQIACPIFAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLAVRVFNTYFG---HYFlklsLVGWGLPALmVIGTGSANSYGLYTIRdrenrtslELCWFR 423
Cdd:cd16007   76 FFFLAAFSWLCLEGVQLYLMLVEVFESEYSrkkYYY----LCGYCFPAL-VVGISAAIDYRSYGTE--------KACWLR 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 424 egttmyalyitVHGYFLITFLfGMVVLALVVWKIFTLS------RATAV----KERGKNRKK-VLTLLGLSSLVGVTW-- 490
Cdd:cd16007  143 -----------VDNYFIWSFI-GPVSFVIVVNLVFLMVtlhkmiRSSSVlkpdSSRLDNIKSwALGAITLLFLLGLTWaf 210
                        250       260
                 ....*....|....*....|....*..
gi 229093087 491 GLAIFTPLGLSTVYIFALFNSLQGVFI 517
Cdd:cd16007  211 GLLFINKESVVMAYLFTTFNAFQGMFI 237
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
266-524 1.24e-18

Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; member of the class B2 family of seven-transmembrane G protein-coupled receptors; ETL (EGF-TM7-latrophilin-related protein) belongs to Group I adhesion GPCRs, which also include latrophilins (also called lectomedins or latrotoxin receptors). 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. ETL, for instance, contains EGF-like repeats, which also present in other EGF-TM7 adhesion GPCRs, such as Cadherin EGF LAG seven-pass G-type receptors (CELSR1-3), EGF-like module receptors (EMR1-3), CD97, and Flamingo. ETL is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. 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.


Pssm-ID: 320553 [Multi-domain]  Cd Length: 258  Bit Score: 85.70  E-value: 1.24e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 266 HILTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSedapkIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVF 345
Cdd:cd15437    2 NVLTRITQLGIIISLICLSMCIFTFWFFSEIQSTRTT-----IHKNLCCSLFLAELIFLI--GINMNANKLFCSIIAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 346 HYFLLCAFTWMGLEAFHLYLLAVRV-FNTYFGHYflKLSLVGWGLPALmVIGTGSANSYGLYtirdrenrTSLELCWFRE 424
Cdd:cd15437   75 HYFFLAAFAWMCIEGIHLYLIVVGViYNKGFLHK--NFYIFGYGSPAV-VVGISAALGYKYY--------GTTKVCWLST 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 425 GTTMYALYItvhGYFLITFLFGMVVLALVVWKIFtlsRATAVKERGKN-----RKKVLTLLGLSSLVGVTWGLAIFTPLG 499
Cdd:cd15437  144 ENNFIWSFI---GPACLIILVNLLAFGVIIYKVF---RHTAMLKPEVScyeniRSCARGALALLFLLGATWIFGVLHVVY 217
                        250       260
                 ....*....|....*....|....*..
gi 229093087 500 LSTV--YIFALFNSLQGVFICCWFTIL 524
Cdd:cd15437  218 GSVVtaYLFTISNAFQGMFIFIFLCVL 244
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
267-524 5.10e-17

Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled receptors; 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 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.


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 81.14  E-value: 5.10e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRLSRErfkseDAPKIHVALGGSLFLLNLAFLVNVGSGSKgsDAACWARGAVFH 346
Cdd:cd16005    3 LLDVITWVGILLSLVCLLICIFTFCFFRGLQS-----DRNTIHKNLCISLFVAELLFLIGINRTDQ--PIACAVFAALLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLAVRVFNTYFGH--YFLklsLVGWGLPALMVIGTGSAN--SYGlytirdrenrtSLELCWF 422
Cdd:cd16005   76 FFFLAAFTWMFLEGVQLYIMLVEVFESEHSRrkYFY---LVGYGMPALIVAVSAAVDyrSYG-----------TDKVCWL 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 423 REGTTMYALYItvhGYFLITFLFGMVVLALVVWKIFTLSrATAVKERG---KNRKKVLTLLGLSSLVGVTW--GLAIFTP 497
Cdd:cd16005  142 RLDTYFIWSFI---GPATLIIMLNVIFLGIALYKMFHHT-AILKPESGcldNIKSWVIGAIALLCLLGLTWafGLMYINE 217
                        250       260
                 ....*....|....*....|....*..
gi 229093087 498 LGLSTVYIFALFNSLQGVFICCWFTIL 524
Cdd:cd16005  218 STVIMAYLFTIFNSLQGMFIFIFHCVL 244
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
267-517 1.07e-16

Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled receptors; 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 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.


Pssm-ID: 320672 [Multi-domain]  Cd Length: 258  Bit Score: 79.96  E-value: 1.07e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRLSRErfkseDAPKIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFH 346
Cdd:cd16006    3 LLTVITWVGIVISLVCLAICIFTFCFFRGLQS-----DRNTIHKNLCINLFIAEFIFLI--GIDKTEYKIACPIFAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLAVRVFNTYFG---HYFLKlslvGWGLPAlMVIGTGSANSYGLYTIRdrenrtslELCWFR 423
Cdd:cd16006   76 FFFLAAFAWMCLEGVQLYLMLVEVFESEYSrkkYYYVA----GYLFPA-TVVGVSAAIDYKSYGTE--------KACWLR 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 424 egttmyalyitVHGYFL------ITFLFGMVVLALVVWKIFTLSRATAVK----ERGKNRKKVLTLLGLSSLVGVTW--G 491
Cdd:cd16006  143 -----------VDNYFIwsfigpVTFIILLNLIFLVITLCKMVKHSNTLKpdssRLENIKSWVLGAFALLCLLGLTWsfG 211
                        250       260
                 ....*....|....*....|....*.
gi 229093087 492 LAIFTPLGLSTVYIFALFNSLQGVFI 517
Cdd:cd16006  212 LLFINEETIVMAYLFTIFNAFQGMFI 237
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
267-517 1.45e-16

Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; 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 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.


Pssm-ID: 320552 [Multi-domain]  Cd Length: 258  Bit Score: 79.84  E-value: 1.45e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRLSRErfkseDAPKIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFH 346
Cdd:cd15436    3 LLFVITWVGIVISLVCLLICIFTFCFFRGLQT-----DRNTIHKNLCINLFIAELLFLI--GINRTQYTIACPIFAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 347 YFLLCAFTWMGLEAFHLYLLAVRVFNTYFGH--YFLklsLVGWGLPALmVIGTGSANSYGLYtirdrenrTSLELCWFRe 424
Cdd:cd15436   76 FFFLAAFCWLCLEGVQLYLLLVEVFESEYSRrkYFY---LCGYSFPAL-VVAVSAAIDYRSY--------GTEKACWLR- 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 425 gttmyalyitVHGYFLITFL--FGMVVLALVVWKIFTLSR----ATAVKERGKN----RKKVLTLLGLSSLVGVTW--GL 492
Cdd:cd15436  143 ----------VDNYFIWSFIgpVTFVITLNLVFLVITLHKmvshSDLLKPDSSRldniKSWALGAIALLFLLGLTWsfGL 212
                        250       260
                 ....*....|....*....|....*
gi 229093087 493 AIFTPLGLSTVYIFALFNSLQGVFI 517
Cdd:cd15436  213 MFINEESVVMAYLFTIFNAFQGVFI 237
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
281-517 3.28e-16

cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. 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. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. 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. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuron migration and axon guidance in the CNS.


Pssm-ID: 320557 [Multi-domain]  Cd Length: 254  Bit Score: 78.45  E-value: 3.28e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 281 IFLAFTIILYAFLRLSRERFKSEDAPKIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFHYFLLCAFTWMGLEA 360
Cdd:cd15441   12 IGISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELLFLL--GINQTENLFPCKLIAILLHYFYLSAFSWLLVES 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 361 FHLYLLAVRVFNTYFGH---YFlklsLVGWGLPALMVigtgsANSYGLYTirdrENRTSLELCWfregttmyalyITVHG 437
Cdd:cd15441   90 LHLYRMLTEPRDINHGHmrfYY----LLGYGIPAIIV-----GLSVGLRP----DGYGNPDFCW-----------LSVNE 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 438 YFLITF---LFGMVVLALVVWkIFTLSRATAVKERGKNRKKVLTLLGLSS----LVGVTWGLAIFTPLGLSTV--YIFAL 508
Cdd:cd15441  146 TLIWSFagpIAFVIVITLIIF-ILALRASCTLKRHVLEKASVRTDLRSSFlllpLLGATWVFGLLAVNEDSELlhYLFAG 224

                 ....*....
gi 229093087 509 FNSLQGVFI 517
Cdd:cd15441  225 LNFLQGLFI 233
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
268-517 1.08e-15

Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. 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. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. 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.


Pssm-ID: 320657 [Multi-domain]  Cd Length: 254  Bit Score: 77.19  E-value: 1.08e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSedapkIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFHY 347
Cdd:cd15991    4 LKIITYTTVSLSLVALLITFILLVLIRTLRSNLHS-----IHKNLVAALFFSELIFLI--GINQTENPFVCTVVAILLHY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 348 FLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLkLSLVGWGLPALMVigtgsansyGLYTIRDRENRTSLELCWfregtt 427
Cdd:cd15991   77 FYMSTFAWMFVEGLHIYRMLTEVRNINTGHMRF-YYVVGWGIPAIIT---------GLAVGLDPQGYGNPDFCW------ 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 428 myalyITVHGYFLITFLFGMVVLALVVWKIFTLSRATAV--KERGKNRKKVLTLLG----LSSLVGVTW--GLAIFTPLG 499
Cdd:cd15991  141 -----LSVQDTLIWSFAGPIGIVVIINTVIFVLAAKASCgrRQRYFEKSGVISMLRtaflLLLLISATWllGLMAVNSDT 215
                        250
                 ....*....|....*...
gi 229093087 500 LSTVYIFALFNSLQGVFI 517
Cdd:cd15991  216 LSFHYLFAIFSCLQGIFI 233
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
268-517 1.57e-15

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.


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 76.50  E-value: 1.57e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLR----LSRERFKsedapkIHVALGGSLFLLNLAFLVNVGSGSkgSDAACWARGA 343
Cdd:cd15256    4 LSSITYVGCSLSIFCLAITLVTFAVLSsvstIRNQRYH------IHANLSFAVLVAQILLLISFRFEP--GTLPCKIMAI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 344 VFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSlVGWGLPALM-VIGTGSA-NSYGlytirDRENrtslelCW 421
Cdd:cd15256   76 LLHFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYG-IGWGSPLLIcIISLTSAlDSYG-----ESDN------CW 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 422 FR-EGTTMYAlyitvhgyFLITFLFGMVV---LALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSL---VGVTWGLAI 494
Cdd:cd15256  144 LSlENGAIWA--------FVAPALFVIVVnigILIAVTRVISRISADNYKVHGDANAFKLTAKAVAVLlpiLGSSWVFGV 215
                        250       260
                 ....*....|....*....|....*
gi 229093087 495 FTPLGLSTV--YIFALFNSLQGVFI 517
Cdd:cd15256  216 LAVNTHALVfqYMFAIFNSLQGFFI 240
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
265-517 2.17e-15

The subfamily B1 of hormone receptors (secretin-like), member of the class B family seven-transmembrane G protein-coupled receptors; The B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of this subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. Moreover, the B1 subfamily receptors play key roles in hormone homeostasis and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzheimer###s and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression). Furthermore, the subfamilies B2 and B3 consist of receptors that are capable of interacting with epidermal growth factors (EGF) and the Drosophila melanogaster Methuselah gene product (Mth), respectively. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 341321 [Multi-domain]  Cd Length: 273  Bit Score: 76.49  E-value: 2.17e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 265 VHILTRISQAGCGVSMIFLAFTI-ILYAFLRLSRERFKsedapkIHVALGGSL-----------FLLNLAFLVNVGSGSK 332
Cdd:cd15041    1 LLVVYYIYLVGYSLSLVALLPAIvIFLYFRSLRCTRIR------LHINLFLSFilravfwiiwdLLVVYDRLTSSGVETV 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 333 GSDAACWARGAVF--HYFLLCAFTWMGLEAFHLYLLAVRVFNTYfGHYFLKLSLVGWGLPALMVIgtgsANSYGLYTIRD 410
Cdd:cd15041   75 LMQNPVGCKLLSVlkRYFKSANYFWMLCEGLYLHRLIVVAFFSE-PSSLKLYYAIGWGLPLVIVV----IWAIVRALLSN 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 411 renrtslELCWfREGTTMYALYItVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTW 490
Cdd:cd15041  150 -------ESCW-ISYNNGHYEWI-LYGPNLLALLVNLFFLINILRILLTKLRSHPNAEPSNYRKAVKATLILIPLFGIQY 220
                        250       260       270
                 ....*....|....*....|....*....|..
gi 229093087 491 GLAIFTP---LGLSTVYIF--ALFNSLQGVFI 517
Cdd:cd15041  221 LLTIYRPpdgSEGELVYEYfnAILNSSQGFFV 252
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
267-524 2.54e-15

orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group VI adhesion GPCRs consist of orphan receptors GPR110, GPR111, GPR113, GPR115, GPR116, and closely related proteins. 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. GPR110 possesses a SEA box in the N-terminal has been identified as an oncogene over-expressed in lung and prostate cancer. GPR113 contains a hormone binding domain and one EGF (epidermal grown factor) domain. GPR112 has extremely long N-terminus (about 2,400 amino acids) containing a number of Ser/Thr-rich glycosylation sites and a pentraxin (PTX) domain. GPR116 has two C2-set immunoglobulin-like repeats, which is found in the members of the immunoglobulin superfamily of cell surface proteins, and a SEA (sea urchin sperm protein, enterokinase, and a grin)-box, which is present in the extracellular domain of the transmembrane mucin (MUC) family and known to enhance O-glycosylation. 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.


Pssm-ID: 320598 [Multi-domain]  Cd Length: 268  Bit Score: 76.20  E-value: 2.54e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRlsRERFKSEDAPKIHVAL---GGSLFLLNLAFLVNVG-SGSKGSDAACWARG 342
Cdd:cd15932    3 ALDYITYVGLGISILSLVLCLIIEALVW--KSVTKNKTSYMRHVCLvniALSLLIADIWFIIGAAiSTPPNPSPACTAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 343 AVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSL-VGWGLPALM-VIGTGSANSYGLYTirdRENrtsleLC 420
Cdd:cd15932   81 FFIHFFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIAFsLGYGCPLIIaIITVAATAPQGGYT---RKG-----VC 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 421 WFREGTTM--YALYITVhgyfLITFLFGMVVLALVvwkIFTLSRATAVKERGKNRKKVL-----TLLGLSSLVGVTWGLA 493
Cdd:cd15932  153 WLNWDKTKalLAFVIPA----LAIVVVNFIILIVV---IFKLLRPSVGERPSKDEKNALvqigkSVAILTPLLGLTWGFG 225
                        250       260       270
                 ....*....|....*....|....*....|....
gi 229093087 494 IFT---PLGLSTVYIFALFNSLQGVFICCWFTIL 524
Cdd:cd15932  226 LGTmidPKSLAFHIIFAILNSFQGFFILVFGTLL 259
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
214-255 5.65e-15

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.


Pssm-ID: 460350  Cd Length: 44  Bit Score: 68.87  E-value: 5.65e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 229093087  214 TCVFWDVTKGTTGDWSSEGCSTEVRPEG-TVCCCDHLTFFALL 255
Cdd:pfam01825   2 QCVFWDFTNSTTGRWSTEGCTTVSLNDThTVCSCNHLTSFAVL 44
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
268-517 9.28e-14

orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR113 is an orphan receptor that belongs to group VI adhesion-GPCRs along with GPR110, GPR111, GPR115, and GPR116. 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. GPR113 contains a hormone binding domain and one EGF (epidermal grown factor) domain, and is primarily expressed in a subset of taste receptor cells. 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.


Pssm-ID: 320381 [Multi-domain]  Cd Length: 271  Bit Score: 71.72  E-value: 9.28e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKS---EDAPKIHVALggSLFLLNLAFLVNVGSGSKGSDAACWARGAV 344
Cdd:cd15253    4 LDFLSQVGLGASILALLLCLGIYRLVWRSVVRNKIsyfRHMTLVNIAF--SLLLADTCFLGATFLSAGHESPLCLAAAFL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 345 FHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSL-VGWGLPALMVIGTgsansYGLYTIRDRENRTSLelCWFR 423
Cdd:cd15253   82 CHFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVtLGYLCPLLIAAAT-----VAYYYPKRQYLHEGA--CWLN 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 424 -EGTTMYALYITVhgyfLITFLFGMVVLALVVWKIF--TLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPLGL 500
Cdd:cd15253  155 gESGAIYAFSIPV----LAIVLVNLLVLFVVLMKLMrpSVSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLTGE 230
                        250       260
                 ....*....|....*....|
gi 229093087 501 S---TVYIFALFNSLQGVFI 517
Cdd:cd15253  231 SsqvSHYGFAILNAFQGVFI 250
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
266-517 8.78e-13

corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320392 [Multi-domain]  Cd Length: 265  Bit Score: 68.60  E-value: 8.78e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 266 HILTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSedapkIHVALGGSLFLLNLAFLV--NVGSGSKGSDAACWAR-- 341
Cdd:cd15264    2 KVALIIYYLGFSISLVALAVALIIFLYFRSLRCLRNN-----IHCNLIVTFILRNVTWFImqNTLTEIHHQSNQWVCRli 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 342 GAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNT---YFGHYFLklslVGWGLPALMVIGTGSANSYglytirdRENrtslE 418
Cdd:cd15264   77 VTVYNYFQVTNFFWMFVEGLYLHTMIVWAYSAdkiRFWYYIV----IGWCIPCPFVLAWAIVKLL-------YEN----E 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 419 LCWFREGTTMYALYItVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPL 498
Cdd:cd15264  142 HCWLPKSENSYYDYI-YQGPILLVLLINFIFLFNIVWVLITKLRASNTLETIQYRKAVKATLVLLPLLGITYMLFFINPG 220
                        250       260
                 ....*....|....*....|....
gi 229093087 499 GLSTVYI-FALFN----SLQGVFI 517
Cdd:cd15264  221 DDKTSRLvFIYFNtflqSFQGLFV 244
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
271-521 2.50e-12

insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Nilaparvata lugens (brown planthopper) and its closely related proteins from mollusks and annelid worms. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320388 [Multi-domain]  Cd Length: 267  Bit Score: 67.30  E-value: 2.50e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 271 ISQAGCGVSMIFLAFT-IILYAF--LRLSRERfksedapkIHV------ALGGSLFLLNLAFLVNVGSGSKGSDAACWAR 341
Cdd:cd15260    7 VYIGGYSVSLIALIISlAIFFSFrsLRCTRIT--------IHMnlfisfALNNLLWIVWYKLVVDNPEVLLENPIWCQAL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 342 GAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTyfGHYFLKLSLV-GWGLPALMV-IGTGSANSYGLYTIRdrenrtslel 419
Cdd:cd15260   79 HVLLQYFMVCNYFWMFCEGLYLHTVLVVAFIS--EKSLMRWFIAiGWGVPLVITaIYAGVRASLPDDTER---------- 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 420 CWFREGTTMYALYITVHGYFLITFLFGMVVLALVVWKiftLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPLG 499
Cdd:cd15260  147 CWMEESSYQWILIVPVVLSLLINLIFLINIVRVLLTK---LRATSPNPAPAGLRKAVRATLILIPLLGLQFLLIPFRPEP 223
                        250       260
                 ....*....|....*....|....*..
gi 229093087 500 ---LSTVY--IFALFNSLQGVFICCWF 521
Cdd:cd15260  224 gapLETIYqyVSALLTSLQGLCVAVLF 250
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
268-517 2.85e-12

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.


Pssm-ID: 320597 [Multi-domain]  Cd Length: 262  Bit Score: 67.15  E-value: 2.85e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLRLSRerfKSEDAPKIHVALggSLFLLNLAFLVNVGSgsKGSDAACWARGAVFHY 347
Cdd:cd15931    4 LEWINRVGVIVSLFCLGLAIFTFLLCRWIP---KINTTAHLHLCL--CLSMSHTLFLAGIEY--VENELACTVMAGLLHY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 348 FLLCAFTWMGLEAFHLYLLAVRVFNTYF----GHYFLKLSLVGWGLPALMVIGTGSANSYGLytirDRENRtslelCWFR 423
Cdd:cd15931   77 LFLASFVWMLLEALQLHLLVRRLTKVQViqrdGLPRPLLCLIGYGVPFLIVGVSALVYSDGY----GEAKM-----CWLS 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 424 EGTTMYALYItvhGYFLITFLFGMVVLALVVWKIF-TLSRATA-VKERGKNRKKVLTLLGLSSLVGVTW--GLAIFTPLG 499
Cdd:cd15931  148 QERGFNWSFL---GPVIAIIGINWILFCATLWCLRqTLSNMNSdISQLKDTRLLTFKAVAQLFILGCTWvlGLFQTNPVA 224
                        250
                 ....*....|....*...
gi 229093087 500 LSTVYIFALFNSLQGVFI 517
Cdd:cd15931  225 LVFQYLFTILNSLQGAFL 242
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
271-517 1.18e-11

Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. 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. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. 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.


Pssm-ID: 320658  Cd Length: 255  Bit Score: 65.23  E-value: 1.18e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 271 ISQAGCGVSMIFLAFTIILYAFLRLSRERFKSedapkIHVALGGSLFLLNLAFLVNVGSGSkgSDAACWARGAVFHYFLL 350
Cdd:cd15992    7 LTWSSVGVTLGFLLLTFLFLLCLRALRSNKTS-----IRKNGATALFLSELVFILGINQAD--NPFACTVIAILLHFFYL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 351 CAFTWMGLEAFHLYLLAVRVFNTYFG---HYFlklsLVGWGLPALMVigtgsansyGLYTIRDRENRTSLELCWFregtt 427
Cdd:cd15992   80 CTFSWLFLEGLHIYRMLSEVRDINYGpmrFYY----LIGWGVPAFIT---------GLAVGLDPEGYGNPDFCWL----- 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 428 myALYITVHGYFL--ITFLFGMVVLALVVwkiftLSRATAVKERGKNRKKVLTLLGLSS------LVGVTWGLAIFTPLG 499
Cdd:cd15992  142 --SIYDTLIWSFAgpVAFAVSMNVFLYIL-----SSRASCSAQQQSFEKKKGPVSGLRTaftvllLVSVTCLLALLSVNS 214
                        250       260
                 ....*....|....*....|
gi 229093087 500 LSTV--YIFALFNSLQGVFI 517
Cdd:cd15992  215 DVILfhYLFAGFNCLQGPFI 234
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
265-518 1.61e-11

insect diuretic hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors that specifically bind to insect diuretic hormones found in Manduca sexta (moth) and Acheta domesticus (the house cricket), among others. Insect diuretic hormone and their GPCRs play critical roles in the regulation of water and ion balance. Thus they are attractive targets for developing new insecticides. Activation of the diuretic hormone receptors stimulate adenylate cyclase, thereby increasing cAMP levels in Malpighian tube. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of Gs family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx.


Pssm-ID: 320391 [Multi-domain]  Cd Length: 272  Bit Score: 65.08  E-value: 1.61e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 265 VHILTRISQAGCGVSMIFLAFTIILYAF---LRLSRERfksedapkIHVALGGSLFLLNLAFLVN-VGSGSKGSD-AACW 339
Cdd:cd15263    1 VEVTTTIYFIGYSLSLVALSLALWIFLYfkdLRCLRNT--------IHTNLMFTYILADLTWILTlTLQVSIGEDqKSCI 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 340 ARGAVFHYFLLCAFTWMGLEAFHLYLLAVRVF---NTYFGHYflklSLVGWGLPALMVIGTGSANSYG-LYTIRDRENRT 415
Cdd:cd15263   73 ILVVLLHYFHLTNFFWMFVEGLYLYMLVVETFsgeNIKLRVY----AFIGWGIPAVVIVIWAIVKALApTAPNTALDPNG 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 416 SLELC-WFREgttmyALYITVHGYFLITFLF-GMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLA 493
Cdd:cd15263  149 LLKHCpWMAE-----HIVDWIFQGPAILVLAvNLVFLVRIMWVLITKLRSANTVETQQYRKAAKALLVLIPLLGITYILV 223
                        250       260       270
                 ....*....|....*....|....*....|...
gi 229093087 494 IFTPLGLSTVYIF----ALFNSLQG----VFIC 518
Cdd:cd15263  224 IAGPTEGIAANIFeyvrAVLLSTQGftvaLFYC 256
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
275-524 1.26e-10

brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, 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 mediate 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.


Pssm-ID: 320379  Cd Length: 253  Bit Score: 61.89  E-value: 1.26e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 275 GCGVS-MIFLAFTIILYAFLRLsrerFKSEDAPkihVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVFHYFLLCAF 353
Cdd:cd15251   11 GCGVScLALLTLLAIYAAFWRY----IRSERSI---ILINFCLSIISSNILILVGQTQTLNKGVCTMTAAFLHFFFLSSF 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 354 TWMGLEAFHLYLLAV-RVFNTYFGHYFLKLslvGWGLPALMV---IGTGSANSYGlytirdrenrtSLELCWFR-EGTTM 428
Cdd:cd15251   84 CWVLTEAWQSYMAVTgRMRTRLIRKRFLCL---GWGLPALVVavsVGFTRTKGYG-----------TSSYCWLSlEGGLL 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 429 YALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKErgkNRKKVLTLLGLSSLVGVtwgLAIFTPLGLSTVYIFAL 508
Cdd:cd15251  150 YAFVGPAAAVVLVNMVIGILVFNKLVSRDGISDNAMASLW---SSCVVLPLLALTWMSAV---LAMTDRRSVLFQILFAV 223
                        250
                 ....*....|....*.
gi 229093087 509 FNSLQGVFICCWFTIL 524
Cdd:cd15251  224 FDSLQGFVIVMVHCIL 239
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
212-256 6.24e-09

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


Pssm-ID: 197639  Cd Length: 49  Bit Score: 52.00  E-value: 6.24e-09
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 229093087   212 TLTCVFWDvtkGTTGDWSSEGCSTEVRPEG-TVCCCDHLTFFALLL 256
Cdd:smart00303   2 NPICVFWD---ESSGEWSTRGCELLETNGThTTCSCNHLTTFAVLM 44
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
260-524 9.25e-09

brain-specific angiogenesis inhibitor 1, 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.


Pssm-ID: 320656  Cd Length: 267  Bit Score: 56.54  E-value: 9.25e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 260 LDQSTVHILTRIsqAGCGVSMIFLAFTIILYaflrLSRERFKSEDAPKIHVALGGSLFLLNLafLVNVGSGSKGSDAACW 339
Cdd:cd15990    1 MEKALLPSVTLI--VGCGVSSLTLLLLIIIY----VSVWRYIRSERSVILINFCLSIISSNA--LILIGQTQTRNKVVCT 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 340 ARGAVFHYFLLCAFTWMGLEAFHLYLLAV-RVFNTYFGHYFLKLslvGWGLPALMV---IGTGSANSYGlytirdrenrt 415
Cdd:cd15990   73 LVAAFLHFFFLSSFCWVLTEAWQSYMAVTgRLRNRIIRKRFLCL---GWGLPALVVaisVGFTKAKGYG----------- 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 416 SLELCWFR-EGTTMYALYitvhGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAI 494
Cdd:cd15990  139 TVNYCWLSlEGGLLYAFV----GPAAAVVLVNMVIGILVFNKLVSKDGITDKKLKERAGASLWSSCVVLPLLALTWMSAV 214
                        250       260       270
                 ....*....|....*....|....*....|...
gi 229093087 495 FTPLGLSTVY---IFALFNSLQGVFICCWFTIL 524
Cdd:cd15990  215 LAITDRRSALfqiLFAVFDSLEGFVIVMVHCIL 247
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
262-517 9.83e-09

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR144 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR133. 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.


Pssm-ID: 320383 [Multi-domain]  Cd Length: 263  Bit Score: 56.40  E-value: 9.83e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 262 QSTVHILTRIsqaGCGVSMIFLAFTIILYAFLRLSRErfkseDAPKIHVALggsLFLLNLA-FLVNVGSGSKGSDAACWA 340
Cdd:cd15255    1 EATLRTLSFI---GCGVSLCALIVTFILFLAVGVPKS-----ERTTVHKNL---IFALAAAeFLLMFSEWAKGNQVACWA 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 341 RGAVFHYFLLCAFTWMGLEAFHLYLLAVRVfNTYFGHYFLKLSLVGWGLPaLMVIGTGSANSYGLYTIRDRenrtslelC 420
Cdd:cd15255   70 VTALLHLFFLAAFSWMLVEGLLLWSKVVAV-NMSEDRRMKFYYVTGWGLP-VVIVAVTLATSFNKYVADQH--------C 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 421 WFREGTTMYALYItvhGYFLITFLFGMVVLALVVwkIFTLS----RATAVKERGKNRKKVLTL--------LGLSSLVGV 488
Cdd:cd15255  140 WLNVQTDIIWAFV---GPVLFVLTVNTFVLFRVV--MVTVSsarrRAKMLTPSSDLEKQIGIQiwatakpvLVLLPVLGL 214
                        250       260
                 ....*....|....*....|....*....
gi 229093087 489 TWGLAIFTPLGLSTVYIFALFNSLQGVFI 517
Cdd:cd15255  215 TWLCGVLVHLSDVWAYVFITLNSFQGLYI 243
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
275-450 9.91e-09

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.


Pssm-ID: 320654 [Multi-domain]  Cd Length: 291  Bit Score: 56.89  E-value: 9.91e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 275 GCGVS-MIFLAFTIILYAFLRLsrerFKSEDAPkihVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVFHYFLLCAF 353
Cdd:cd15988   11 GCAVScMALLILLAIYAAFWRF----IRSERSI---ILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFLSSF 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 354 TWMGLEAFHLYLLAV-RVFNTYFGHYFLKLslvGWGLPALMV---IGTGSANSYGlytirdrenrtSLELCWFR-EGTTM 428
Cdd:cd15988   84 CWVLTEAWQSYLAVIgRMRTRLVRKRFLCL---GWGLPALVVavsVGFTRTKGYG-----------TASYCWLSlEGGLL 149
                        170       180
                 ....*....|....*....|..
gi 229093087 429 YALYITVHGYFLITFLFGMVVL 450
Cdd:cd15988  150 YAFVGPAAVIVLVNMLIGIIVF 171
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
268-524 1.43e-08

Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuronal migration and axon guidance in the CNS. 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. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. 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.


Pssm-ID: 320659 [Multi-domain]  Cd Length: 254  Bit Score: 56.00  E-value: 1.43e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLRLSRERFKSedapkIHVALGGSLFLLNLAFLVnvGSGSKGSDAACWARGAVFHY 347
Cdd:cd15993    4 LAIVTYSSVSASLAALVLTFSVLTCLRGLKSNTRG-----IHSNIAAALFLSELLFLL--GINRTENQFLCTVVAILLHY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 348 FLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLvGWGLPALMVigtgsansyGLYTIRDRENRTSLELCWfregtt 427
Cdd:cd15993   77 FFLSTFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAI-GWGVPAIIT---------GLAVGLDPEGYGNPDFCW------ 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 428 myalyITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSS------LVGVTW--GLAIFTPLG 499
Cdd:cd15993  141 -----ISIHDKLVWSFAGPIVVVIVMNGVMFLLVARMSCSPGQKETKKTSVLMTLRSsfllllLISATWlfGLLAVNNSV 215
                        250       260
                 ....*....|....*....|....*
gi 229093087 500 LSTVYIFALFNSLQGVFICCWFTIL 524
Cdd:cd15993  216 LAFHYLHAILCCLQGLAVLLLFCVL 240
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
266-524 4.56e-08

corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320561 [Multi-domain]  Cd Length: 265  Bit Score: 54.56  E-value: 4.56e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 266 HILTRISQAGCGVSMIFLAFTIILyaFLRLSRERFKSEdapKIHVALGGSLFLLNLA-FLVNVGSGSKGSDA-ACWAR-- 341
Cdd:cd15445    2 HIAVIINYLGHCISLVALLVAFVL--FLRLRSIRCLRN---IIHWNLITAFILRNATwFVVQLTMSPEVHQSnVVWCRlv 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 342 GAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSlVGWGLPALMVIGTGSANSYglytiRDRENrtslelCW 421
Cdd:cd15445   77 TAAYNYFHVTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFIC-IGWCIPFPIIVAWAIGKLY-----YDNEK------CW 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 422 FREGTTMYALYItVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTP---- 497
Cdd:cd15445  145 FGKRAGVYTDYI-YQGPMILVLLINFIFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPgede 223
                        250       260
                 ....*....|....*....|....*...
gi 229093087 498 -LGLSTVYIFALFNSLQGVFICCWFTIL 524
Cdd:cd15445  224 iSRIVFIYFNSFLESFQGFFVSVFYCFL 251
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
339-524 5.22e-07

corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 51.11  E-value: 5.22e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 339 WAR--GAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLsLVGWGLPALMVIGTGSANSYglytirdRENrts 416
Cdd:cd15446   71 WCRciTTIYNYFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFL-FIGWCIPCPIIVAWAIGKLY-------YEN--- 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 417 lELCWFREGTTMYALYItVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFT 496
Cdd:cd15446  140 -EQCWFGKEPGKYIDYI-YQGPVILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVN 217
                        170       180       190
                 ....*....|....*....|....*....|...
gi 229093087 497 P-----LGLSTVYIFALFNSLQGVFICCWFTIL 524
Cdd:cd15446  218 PgeddiSQIVFIYFNSFLQSFQGFFVSVFYCFL 250
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
315-517 4.68e-06

parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone 2 receptor (PTH2R), one of the three subtypes of PTH receptor family, is found in mammals and fish, but not in chicken or frog. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39) but not by PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs. These results suggest that TIP-39 is a natural ligand for PTH2R. Conversely, PTH1R is activated by PTH and PTHrP, but not by TIP-39. The PTH family receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320648 [Multi-domain]  Cd Length: 289  Bit Score: 48.39  E-value: 4.68e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 315 SLFLLNLAFLVNVGSGSKGSDAACWARGAVFHYFLLCAFTWMGLEAFHLYLLavrVFNTYFG--HYFLKLSLVGWGLPAL 392
Cdd:cd15982   72 AVLMNDFQNAVDAPPVDKSQYVGCKIAVVMFIYFLATNYYWILVEGLYLHSL---IFVAFFSdtKYLWGFTLIGWGFPAV 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 393 MVIGTGSANSyglyTIRDREnrtslelCWFREGTTMYALY----ITVHGYFLITFLFGMVVLALVVWKiftlSRATAVKE 468
Cdd:cd15982  149 FVAAWAVVRA----TLADAR-------CWELSAGDIKWIYqapiLAAIGLNFILFLNTVRVLATKIWE----TNAVGYDT 213
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 229093087 469 RGKNRKKVLTLLGLSSLVGVTWGLAI-----FTPLGLST-VYIFALFNSLQGVFI 517
Cdd:cd15982  214 RKQYRKLAKSTLVLVLVFGVHYIVFVclphtFTGLGWEIrMHCELFFNSFQGFFV 268
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
320-517 1.07e-05

parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone (PTH) receptor family has three subtypes: PTH1R, PTH2R and PTH3R. PTH1R is expressed in bone and kidney and is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to G(s)-protein that in turn activates adenylate cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple intracellular signaling pathways. PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. PTH3R is found in chicken and fish, but it is absent in mammals. The PTH receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320650 [Multi-domain]  Cd Length: 290  Bit Score: 47.25  E-value: 1.07e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 320 NLAFLVNVGSGSKGSDAACWARGAVFHYFLLCAFTWMGLEAFHLYLLavrVFNTYFGH--YFLKLSLVGWGLPALMVIGT 397
Cdd:cd15984   77 DLKSITEAPPADKAQFVGCKVAVTFFLYFLATNYYWILVEGLYLHSL---IFMAFFSEkkYLWGFTLFGWGLPAVFVTIW 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 398 GSANSyglyTIRDREnrtslelCW-FREGTTMYALYITVHGYFLITFLFGMVVLALVVWKIFTlSRATAVKERGKNRKKV 476
Cdd:cd15984  154 ASVRA----TLADTG-------CWdLSAGNLKWIIQVPILAAIVVNFILFINIVRVLATKLRE-TNAGRCDTRQQYRKLL 221
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 229093087 477 LTLLGLSSLVGVTWGLAIFTP-------LGLSTVYIFALFNSLQGVFI 517
Cdd:cd15984  222 KSTLVLMPLFGVHYIVFMAMPytevsgiLWQVQMHYEMLFNSFQGFFV 269
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
274-523 1.30e-05

orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group III adhesion GPCRs include orphan GPR123, GPR124, GPR125, and their closely related proteins. 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. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 also interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Furthermore, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl.


Pssm-ID: 320387 [Multi-domain]  Cd Length: 260  Bit Score: 46.98  E-value: 1.30e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 274 AGCGVSMIFLAFTIILYA----FLRLSRERFksedapkiHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVFHYFL 349
Cdd:cd15259   10 AGAALCLLCLLATIITYIvfhrLIRISRKGR--------HMLVNLCLHLLLTCVVFVGGINRTANQLVCQAVGILLHYST 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 350 LCAFTWMGLEAFHLY-------------LLAVRVFNTYFGHYflklsLVGWGLPaLMVIGTGSANSYGLYTIRDrenrts 416
Cdd:cd15259   82 LCTLLWVGVTARNMYkqvtktakppqdeDQPPRPPKPMLRFY-----LIGWGIP-LIICGITAAVNLDNYSTYD------ 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 417 leLCWFREGTTMYALYITVHgyfLITFLFGMVVLalvvwKIFTLSRATAVKERGKNRKKVLTLLglssLVGVTWGLAIFT 496
Cdd:cd15259  150 --YCWLAWDPSLGAFYGPAA---LIVLVNCIYFL-----RIYCQLKGAPVSFQSQLRGAVITLF----LYVAMWACGALA 215
                        250       260       270
                 ....*....|....*....|....*....|..
gi 229093087 497 -----PLGLSTVYIFALFNSLQGVFICCWFTI 523
Cdd:cd15259  216 vsqryFLDLVFSCLYGATCSSLGLFVLIHHCL 247
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
267-524 2.90e-05

orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR111 and GPR115 are highly homologous orphan receptors that belong to group VI adhesion-GPCRs along with GPR110, GPR113, and GPR116. 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. Both GPR111 and GPR5 are present only in land-living animals and are predominantly expressed in the developing skin.


Pssm-ID: 320660 [Multi-domain]  Cd Length: 267  Bit Score: 45.99  E-value: 2.90e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFLAFTIILYAFLRlsRERFKSEDAPKIHVAL---GGSLFLLNLAFLVNVGSGSKGSD-AACWARG 342
Cdd:cd15994    3 VLDYITRIGLGLSIFSLALCLTIEAVVW--SHVTKTEITYMRHVCIvniATSLLIADVWFILASIVHNTALNyPLCVAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 343 AVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSL-VGWGLPALMVIGTGSANSYGLYTIRDrenrtslELCW 421
Cdd:cd15994   81 FFLHFFYLSLFFWMLTKALLILYGILLVFFKITKSVFIATAFsIGYGCPLVIAVLTVAITEPKKGYLRP-------EACW 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 422 FREGTTMYALYITVHGYFLItfLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLG-LSSLVGVTWGLAIFTPL-- 498
Cdd:cd15994  154 LNWDETKALLAFIIPALSIV--VVNLIVVGVVVVKTQRSSIGESCKQDVSNIIRISKNVAiLTPLLGLTWGFGLATIIds 231
                        250       260
                 ....*....|....*....|....*..
gi 229093087 499 -GLSTVYIFALFNSLQGVFICCWFTIL 524
Cdd:cd15994  232 rSLPFHIIFALLNAFQGFFILLFGTIL 258
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
268-517 3.40e-05

The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR116 (also known as Ig-hepta) is an orphan receptor that belongs to group VI adhesion-GPCRs along with GPR110, GPR111, GPR113, and GPR115. 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. GPR116 has four I-set immunoglobulin-like repeats, which is found in the members of the immunoglobulin superfamily of cell surface proteins, and a SEA (sea urchin sperm protein, enterokinase, and a grin)-box, which is present in the extracellular domain of the transmembrane mucin (MUC) family and known to enhance O-glycosylation. GPR116 is highly expressed in fetal and adult lung, and it has been shown to regulate lung surfactant levels as well as to stimulate breast cancer metastasis through a G(q)-p63-RhoGEF-Rho GTPase signaling pathway. 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.


Pssm-ID: 320382 [Multi-domain]  Cd Length: 275  Bit Score: 45.95  E-value: 3.40e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 268 LTRISQAGCGVSMIFLAFTIILYAFLRLSRErfKSEDAPKIHVAL---GGSLFLLNLAFLVNVGSGSKG---SDAACWAR 341
Cdd:cd15254    4 LDYITYIGLSISILSLAICIVIESLVWKSVT--KNRTSYMRHVCIlniAVSLLIADIWFIVVAAIQDQNyavNGNVCVAA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 342 GAVFHYFLLCAFTWM---GLEAFhlYLLAVRVFNTYFGHYFLKLSLVGWGLP-ALMVIGTGSANSYGLYTirdRENrtsl 417
Cdd:cd15254   82 TFFIHFFYLCVFFWMlalGLMLF--YRLVFILHDTSKTIQKAVAFCLGYGCPlIISVITIAVTLPRDSYT---RKK---- 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 418 eLCW--FREGTTMYALYITVhgyfLITFLFGMVVLALVVWKIftlSRATAVKERGKNRKKVLTLLG-----LSSLVGVTW 490
Cdd:cd15254  153 -VCWlnWEDSKALLAFVIPA----LIIVAVNSIITVVVIVKI---LRPSIGEKPSKQERSSLFQIIksigvLTPLLGLTW 224
                        250       260       270
                 ....*....|....*....|....*....|
gi 229093087 491 GLAIFTPL-GLSTVY--IFALFNSLQGVFI 517
Cdd:cd15254  225 GFGLATVIkGSSIVFhiLFTLLNAFQGLFI 254
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
275-519 6.42e-05

The pigment dispersing factor receptor, member of the class B seven-transmembrane G protein-coupled receptors; The pigment dispersing factor receptor (PDFR) is a G protein-coupled receptor that binds the circadian clock neuropeptide PDF, a functional ortholog of the mammalian vasoactive intestinal peptide (VIP), on the pacemaker neurons. The PDFR is implicated in regulating flight circuit development and in modulating acute flight In Drosophila melanogaster. The PDFR activation stimulates adenylate cyclase, thereby increasing cAMP levels in many different pacemakers, and the receptor signaling has been shown to regulate behavioral circadian rhythms and geotaxis in Drosophila. The PDFR belongs to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. . These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. They play key roles in hormone homeostasis in mammals and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzheimer###s and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression).


Pssm-ID: 320389 [Multi-domain]  Cd Length: 282  Bit Score: 45.05  E-value: 6.42e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 275 GCGVSMIFLAFTIIL---YAFLRLSRERfksedapkIHVALGGSLFLLNLAFLVN------VGSGSKGSDAACWARGAVF 345
Cdd:cd15261   11 GLCLSLVSLIISLFIfsyFRTLRNHRTR--------IHKNLFLAILLQVIIRLVLyidqaiTRSRGSHTNAATTEGRTIN 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 346 HYFLLC-------------AFTWMGLEAFHLY-LLAVRVFNTYFghYFLKLSLVGWGLPALMVIgtgsanSYGLYTIrdr 411
Cdd:cd15261   83 STPILCegfyvlleyaktvMFMWMFIEGLYLHnIIVVSVFSGKP--NYLFYYILGWGIPIVHTS------AWAIVTL--- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 412 eNRTSLELCWFREGTTMYalYITVHG----YFLITFLFGMVVLALVVWKIftlsRATAVKERGKNRKKVLTLLGLSSLVG 487
Cdd:cd15261  152 -IKMKVNRCWFGYYLTPY--YWILEGprlaVILINLFFLLNIIRVLVSKL----RESHSREIEQVRKAVKAAIVLLPLLG 224
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 229093087 488 VTWGLAIFTPLGLSTVYIFALFN-------SLQGVFICC 519
Cdd:cd15261  225 ITNILQMIPPPLTSVIVGFAVWSysthfltSFQGFFVAL 263
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
263-395 3.52e-04

growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor (GHRHR) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide. These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. GHRH is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. GHRHR is found in mammals as well as zebrafish and chicken, whereas the GHRHR type 2, an ortholog of the GHRHR, has only been identified in ray-finned fish, chicken and Xenopus. Xenopus laevis GHRHR2 has been shown to interact with both endogenous GHRH and PACAP-related peptide (PRP).


Pssm-ID: 320398 [Multi-domain]  Cd Length: 268  Bit Score: 42.48  E-value: 3.52e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 263 STVHIltrISQAGCGVSMIFLAFTI-ILYAFLRLSRERfksedaPKIHVALGGSLFLLNLAFLVNVGSGSKGSD------ 335
Cdd:cd15270    2 STVKI---IYTVGYSISIVSLCVAVaILVAFRRLHCPR------NYIHIQLFFTFILKAIAVFIKDAALFQEDDtdhcsm 72
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 229093087 336 --AACWARGAVFHYFLLCAFTWMGLEAFHLYLLAVRVFnTYFGHYFLKLSLVGWGLPALMVI 395
Cdd:cd15270   73 stVLCKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSF-PRGKRYFWWLVLLGWGLPTLCTG 133
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
265-524 4.65e-04

invertebrate parathyroid hormone-related receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes parathyroid hormone (PTH)-related receptors found in invertebrates such as mollusks and annelid worms. The PTH family receptors are members of the B1 subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. The parathyroid hormone type 1 receptor (PTH1R) is found in all vertebrate species and is activated by two polypeptide ligands: parathyroid hormone (PTH), an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to G(s)- protein that in turn activates adenylyl cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple signaling pathways.


Pssm-ID: 320400 [Multi-domain]  Cd Length: 285  Bit Score: 42.38  E-value: 4.65e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 265 VHILTRIsqaGCGVSMIFL--AFTIILYaFLRLSRERfksedaPKIHVALGGS-------------LFLLNLAFLVNVGS 329
Cdd:cd15272    4 IRLMYNI---GYGLSLVSLliAVIIMLY-FKKLHCPR------NTIHINLFVSfilravlsfikenLLVQGVGFPGDVYY 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 330 GSKG--------SDAACWARGAVFHYFLLCAFTWMGLEAFHLY-LLAVRVF--NTYFGHYFlklsLVGWGLPALMVIgtg 398
Cdd:cd15272   74 DSNGviefkdegSHWECKLFFTMFNYILGANYMWIFVEGLYLHmLIFVAVFseNSRVKWYI----LLGWLSPLLFVL--- 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 399 sansyGLYTIRDRENRTsleLCWfreGTTMYALYI-TVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVL 477
Cdd:cd15272  147 -----PWVFVRATLEDT---LCW---NTNTNKGYFwIIRGPIVISIAINFLFFINIVRVLFTKLKASNTQESRPFRYRKL 215
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 229093087 478 --TLLGLSSLVGVTWGLAIFTPLGLST-------VYIFALFNSLQGVFICCWFTIL 524
Cdd:cd15272  216 akSTLVLIPLFGVHYMVFVVLPDSMSSdeaelvwLYFEMFFNSFQGFIVALLFCFL 271
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
334-394 6.85e-04

secretin receptor-like group of hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group represents G protein-coupled receptors for structurally similar peptide hormones that include secretin, growth-hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide (VIP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Secretin, a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion. Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptors, which are expressed in the brain, pancreas, stomach, kidney, and liver. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. All B1 subfamily GPCRs are able to increase intracellular cAMP levels by coupling to adenylate cyclase via a stimulatory Gs protein. However, depending on its cellular location, some members of subfamily B1 are also capable of coupling to additional G proteins such as G(i/o) and/or G(q) proteins, thereby leading to activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320596 [Multi-domain]  Cd Length: 268  Bit Score: 41.65  E-value: 6.85e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 229093087 334 SDAACWARGAVFHYFLLCAFTWMGLEAFHLYLLAVRVFnTYFGHYFLKLSLVGWGLPALMV 394
Cdd:cd15930   73 STVGCKASMVFFQYCVMANFFWLLVEGLYLHTLLVISF-FSERRYFWWYVLIGWGAPTVFV 132
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
275-454 9.00e-04

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.


Pssm-ID: 320655 [Multi-domain]  Cd Length: 293  Bit Score: 41.59  E-value: 9.00e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 275 GCGVSMIFLAFTIILYAFLrlsrerFKSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVFHYFLLCAFT 354
Cdd:cd15989   13 GCGLSCLALITLAVVYAAL------WRYIRSERSIILINFCLSIISSNILILVGQTQTHNKGICTMTTAFLHFFFLASFC 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 355 WMGLEAFHLYLLAV-RVFNTYFGHYFLKLslvGWGLPALMV---IGTGSANSYGlytirdrenrtSLELCWFR-EGTTMY 429
Cdd:cd15989   87 WVLTEAWQSYMAVTgKIRTRLIRKRFLCL---GWGLPALVVaisMGFTKAKGYG-----------TPHYCWLSlEGGLLY 152
                        170       180
                 ....*....|....*....|....*
gi 229093087 430 ALYITVHGYFLITFLFGMVVLALVV 454
Cdd:cd15989  153 AFVGPAAAVVLVNMVIGILVFNKLV 177
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
328-517 2.31e-03

parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone 3 receptor (PTH3R), one of the three subtypes of PTH receptor family, is found in chicken and fish, but it is absent in mammals. On the other hand, the PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. PTH1R is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39), but not by PTHrP. PTH also strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs, suggesting that TIP-39 is a natural ligand for PTH2R. Conversely, PTH3R binds and responds to both PTH and PTHrP, but not the TIP-39. The PTH family receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320649 [Multi-domain]  Cd Length: 285  Bit Score: 40.29  E-value: 2.31e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 328 GSGSKGSDAACWARGAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYfGHYFLKLSLVGWGLPALMVIGTGSAnsyglyt 407
Cdd:cd15983   80 SPGTRLQWVGCKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSD-KNYLWALTIIGWGLPAVFVSVWASV------- 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 408 irdrenRTSL--ELCWFREGTTMYALY------ITVHGYFLitFLFGMVVLALVVWKiftlSRATAVKERGKNRKKVLTL 479
Cdd:cd15983  152 ------RVSLadTQCWDLSAGNLKWIYqvpilaAILVNFFL--FLNIVRVLASKLWE----TNTGKLDPRQQYRKLLKST 219
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 229093087 480 LGLSSLVGVTWGLAIFTPLGLSTVYIFA-------LFNSLQGVFI 517
Cdd:cd15983  220 LVLMPLFGVHYVLFMAMPYTDVTGLLWQiqmhyemLFNSSQGFFV 264
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
331-457 2.61e-03

glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G protein-coupled receptors; This group represents the glucagon receptor family of G protein-coupled receptors, which includes glucagon receptor (GCGR), glucagon-like peptide-1 receptor (GLP1R), GLP2R, and closely related receptors. These receptors are activated by the members of the glucagon (GCG) peptide family including GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from the large proglucagon precursor. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. Receptors in this group belong to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 341353 [Multi-domain]  Cd Length: 279  Bit Score: 40.11  E-value: 2.61e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 331 SKGSDAACWARGAVFHYFLLCAFTWMGLEAFHLY-LLAVRVFN--TYFGHYFlklsLVGWGLPALMVIGTGSANSygLYt 407
Cdd:cd15929   79 SNQASLGCRVAQVLMQYCVAANYYWLLVEGLYLHtLLVLAVFSerSIFRLYL----LLGWGAPVLFVVPWGIVKY--LY- 151
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 229093087 408 irdrENrtslELCWFREGTTMYALYITVHGYF--LITFLFGMVVLALVVWKI 457
Cdd:cd15929  152 ----EN----TGCWTRNDNMAYWWIIRLPILLaiLINFFIFVRILKILVSKL 195
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
265-521 3.41e-03

calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors for calcitonin (CT) and calcitonin gene-related peptides (CGRPs). Calcitonin, a 32-amino acid peptide hormone, is involved in calcium metabolism in many mammalian species and acts to reduce blood calcium levels and directly inhibits bone resorption by acting on osteoclast. Thus, CT acts as an antagonist to parathyroid hormone and is commonly used in the treatment of bone disorders. The CT receptor is predominantly found in osteoclasts, kidney, and brain, and is primarily coupled to stimulatory G(s) protein, which leads to activation of adenylate cyclase, thereby increasing cAMP production. CGRP, a member of the calcitonin family of peptides, is a potent vasodilator and may contribute to migraine. It is expressed in the peripheral and central nervous system and exists in two forms in humans (alpha-CGRP and beta-CGRP). CGRP meditates its physiological effects through calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), a single transmembrane domain protein. Thus, the CRLR/RAMP1 complex serves as a functional CGRP receptor. On the other hand, the CRLR/RAMP2 and CRLR/RAMP3 complexes function as adrenomedullin-specific receptors. The CT and CGRP receptors belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide.


Pssm-ID: 341343 [Multi-domain]  Cd Length: 274  Bit Score: 39.37  E-value: 3.41e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 265 VHILTRISQAGCGVSMIFLAFTIILYAFLR-LSRERFKSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGA 343
Cdd:cd15274    1 AYNLYYLAIVGHSLSIATLLISLGIFFFFRsLSCQRVTLHKNLFLSYILNSIIIIIHLVAVVPNGELVARNPVSCKILHF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 344 VFHYFLLCAFTWMGLEAFHLY-LLAVRVFNTyfGHYFLKLSLVGWGLPALMVIGTGSANSYglytiRDRENrtslelCWF 422
Cdd:cd15274   81 IHQYMMGCNYFWMLCEGIYLHtLIVVAVFAE--KQRLMWYYLLGWGFPLIPTTIHAITRAV-----YYNDN------CWL 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 423 reGTTMYALYItVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVGVTWGLAIFTPLGLST 502
Cdd:cd15274  148 --SSETHLLYI-IHGPIMAALVVNFFFLLNIVRVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQFVLFPWRPSGKIL 224
                        250       260
                 ....*....|....*....|....*.
gi 229093087 503 V----YIFALFNSLQGVF---ICCWF 521
Cdd:cd15274  225 GkiydYVMHSLIHFQGFFvatIFCFC 250
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
267-517 3.91e-03

insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Nilaparvata lugens (brown planthopper) and its closely related proteins from invertebrates. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320401 [Multi-domain]  Cd Length: 285  Bit Score: 39.28  E-value: 3.91e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 267 ILTRISQAGCGVSMIFL--AFTIIL-YAFLRLSRER-----FKSEDAPKIHVALGGSLFLLNLAFLVNVGS--------- 329
Cdd:cd15273    3 IIKGISQIGYIVSLITLiiAFAIFLsFKKLHCARNKlhmhlFASFILRAFMTLLKDSLFIDGLGLLADIVErngggnevi 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 330 GSKGSDAACWARGAVFHYFLLCAFTWMGLEAFHLYLLAVRVFNTYFGHYFLKLSLvGWGLPALMVIgtgsanSYGLYTIR 409
Cdd:cd15273   83 ANIGSNWVCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILL-GWGLPLIFVV------PWIVARIL 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 410 DRENrtsleLCWfregTT--MYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLLGLSSLVG 487
Cdd:cd15273  156 FENS-----LCW----TTnsNLLNFLIIRIPIMISVLINFILFLNIVRVLLVKLRSSVNEDSRRYKKWAKSTLVLVPLFG 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 229093087 488 VTWglAIFtpLGLS----------TVYIF--ALFNSLQGVFI 517
Cdd:cd15273  227 VHY--TIF--LILSylddtneaveLIWLFcdQLFASFQGFFV 264
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
344-525 4.67e-03

parathyroid hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone (PTH) receptor family has three subtypes: PTH1R, PTH2R and PTH3R. PTH1R is expressed in bone and kidney and is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to a G(s)-protein that in turn activates adenylate cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple intracellular signaling pathways. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39), but not by PTHrP. PTH also strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs, suggesting that TIP-39 is a natural ligand for PTH2R. On the other hand, PTH3R binds and responds to both PTH and PTHrP, but not the TIP-39. Moreover, the PTH3R is more closely related to the PTH1R than PTH2R. PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. The PTH3R is found in chicken and fish, but it is absent in mammals. The PTH receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320393 [Multi-domain]  Cd Length: 289  Bit Score: 39.28  E-value: 4.67e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 344 VFHYFLLCAFTWMGLEAFHLYLLavrVFNTYFG--HYFLKLSLVGWGLPALMVIGTGSANSyglyTIRDRE--NRTSLEL 419
Cdd:cd15265  101 LFLYFLATNYYWILVEGLYLHSL---IFMAFFSdkKYLWGFTLIGWGFPAVFVIPWASVRA----TLADTRcwDLSAGNY 173
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093087 420 CWFREGTTMYALYITvhgyfLITFLFGMVVLALVVWKIFTLSRATavkeRGKNRKKVLTLLGLSSLVGVTWGLAIFTPLG 499
Cdd:cd15265  174 KWIYQVPILAAIVVN-----FILFLNIVRVLATKLRETNAGRCDT----RQQYRKLAKSTLVLIPLFGVHYIVFMGMPYT 244
                        170       180       190
                 ....*....|....*....|....*....|..
gi 229093087 500 LSTV------YIFALFNSLQGVFIccwfTILY 525
Cdd:cd15265  245 EVGLlwqirmHYELFFNSFQGFFV----AIIY 272
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
334-395 5.80e-03

growth-hormone-releasing hormone receptor type 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor type 2 (GHRHR2) is found in non-mammalian vertebrates such as chicken and frog. It is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide, and mammalian growth hormone-releasing hormone. These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Mammalian GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. Mammalian GHRH is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. GHRHR is found in mammals as well as zebrafish and chicken, whereas the GHRHR type 2, an ortholog of the GHRHR, has only been identified in ray-finned fish, chicken and Xenopus. Xenopus laevis GHRHR2 has been shown to interact with both endogenous GHRH and PACAP-related peptide (PRP).


Pssm-ID: 320399 [Multi-domain]  Cd Length: 267  Bit Score: 38.94  E-value: 5.80e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 229093087 334 SDAACWARGAVFHYFLLCAFTWMGLEAFHLYLLAVRVFnTYFGHYFLKLSLVGWGLPALMVI 395
Cdd:cd15271   73 STVACKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTF-TSDRKYFWWYILIGWGAPSVTVT 133
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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