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Conserved domains on  [gi|767989595|ref|XP_011521252|]
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adhesion G-protein coupled receptor G5 isoform X4 [Homo sapiens]

Protein Classification

adhesion G protein-coupled receptor( domain architecture ID 12027402)

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_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
245-518 8.13e-138

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: 399.13  E-value: 8.13e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 245 LAPLTYISLVGCSISIVASLITVLLHFHFRKQS-DSLTRIHMNLHASVLLLNIAFLLSPAFAMSPvPGSACTALAAALHY 323
Cdd:cd15443    1 LEPLTYISIVGCSISAAASLLTILLHFFSRKQPkDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQ-STWLCRAAAALLHY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 324 ALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGPCTIPVfdswenGTGFQNMSI 403
Cdd:cd15443   80 SLLCCLTWMAIEGFHLYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFKREAYGPHTIPT------GTGYQNASM 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 404 CWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAPSVRACHDTVTVLGLTVLLGTTWALAFFSFGVFLLP 483
Cdd:cd15443  154 CWITSSKVHYVLVLGYAGLTSLFNLVVLAWVVRMLRRLRSRKQELGERARRDWVTVLGLTCLLGTTWALAFFSFGVFLIP 233
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 767989595 484 QLFLFTILNSLYGFFLFLWFCSQRCRSEAEAKAQI 518
Cdd:cd15443  234 QLFLFTIINSLYGFFICLWYCTQRRRSDASAKSST 268
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
188-232 1.77e-13

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: 64.64  E-value: 1.77e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 767989595  188 TCVFWKEGARKqpWGGWSPEGCRTEQPSHSQVLCRCNHLTYFAVL 232
Cdd:pfam01825   2 QCVFWDFTNST--TGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
 
Name Accession Description Interval E-value
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
245-518 8.13e-138

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: 399.13  E-value: 8.13e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 245 LAPLTYISLVGCSISIVASLITVLLHFHFRKQS-DSLTRIHMNLHASVLLLNIAFLLSPAFAMSPvPGSACTALAAALHY 323
Cdd:cd15443    1 LEPLTYISIVGCSISAAASLLTILLHFFSRKQPkDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQ-STWLCRAAAALLHY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 324 ALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGPCTIPVfdswenGTGFQNMSI 403
Cdd:cd15443   80 SLLCCLTWMAIEGFHLYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFKREAYGPHTIPT------GTGYQNASM 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 404 CWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAPSVRACHDTVTVLGLTVLLGTTWALAFFSFGVFLLP 483
Cdd:cd15443  154 CWITSSKVHYVLVLGYAGLTSLFNLVVLAWVVRMLRRLRSRKQELGERARRDWVTVLGLTCLLGTTWALAFFSFGVFLIP 233
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 767989595 484 QLFLFTILNSLYGFFLFLWFCSQRCRSEAEAKAQI 518
Cdd:cd15443  234 QLFLFTIINSLYGFFICLWYCTQRRRSDASAKSST 268
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
247-499 4.48e-22

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: 95.42  E-value: 4.48e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595  247 PLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPGS-----ACTALAAAL 321
Cdd:pfam00002   3 SLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLDhcswvGCKVVAVFL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595  322 HYALLSCLTWMAIEGFNLYLLLGRVYNIYiRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNM 401
Cdd:pfam00002  83 HYFFLANFFWMLVEGLYLYTLLVEVFFSE-RKYFWWYLLIGWGVPALVVGIWAGVDPKGYG-----------------ED 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595  402 SICWVRS----------PVVHSVLVmgyggltslfNLVVLAWALWTL-RRLRERADAPSVR--ACHDTVTVLGLTVLLGT 468
Cdd:pfam00002 145 DGCWLSNenglwwiirgPILLIILV----------NFIIFINIVRILvQKLRETNMGKSDLkqYRRLAKSTLLLLPLLGI 214
                         250       260       270
                  ....*....|....*....|....*....|....
gi 767989595  469 TWALAFFSFG---VFLLPQLFLFTILNSLYGFFL 499
Cdd:pfam00002 215 TWVFGLFAFNpenTLRVVFLYLFLILNSFQGFFV 248
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
188-232 1.77e-13

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: 64.64  E-value: 1.77e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 767989595  188 TCVFWKEGARKqpWGGWSPEGCRTEQPSHSQVLCRCNHLTYFAVL 232
Cdd:pfam01825   2 QCVFWDFTNST--TGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
185-237 6.57e-12

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: 60.09  E-value: 6.57e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 767989595   185 YTLTCVFWKEGArkqpwGGWSPEGCRTEQPSHSQVLCRCNHLTYFAVLMQLSP 237
Cdd:smart00303   1 FNPICVFWDESS-----GEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPP 48
 
Name Accession Description Interval E-value
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
245-518 8.13e-138

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: 399.13  E-value: 8.13e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 245 LAPLTYISLVGCSISIVASLITVLLHFHFRKQS-DSLTRIHMNLHASVLLLNIAFLLSPAFAMSPvPGSACTALAAALHY 323
Cdd:cd15443    1 LEPLTYISIVGCSISAAASLLTILLHFFSRKQPkDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQ-STWLCRAAAALLHY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 324 ALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGPCTIPVfdswenGTGFQNMSI 403
Cdd:cd15443   80 SLLCCLTWMAIEGFHLYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFKREAYGPHTIPT------GTGYQNASM 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 404 CWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAPSVRACHDTVTVLGLTVLLGTTWALAFFSFGVFLLP 483
Cdd:cd15443  154 CWITSSKVHYVLVLGYAGLTSLFNLVVLAWVVRMLRRLRSRKQELGERARRDWVTVLGLTCLLGTTWALAFFSFGVFLIP 233
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 767989595 484 QLFLFTILNSLYGFFLFLWFCSQRCRSEAEAKAQI 518
Cdd:cd15443  234 QLFLFTIINSLYGFFICLWYCTQRRRSDASAKSST 268
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
245-516 3.61e-114

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: 338.62  E-value: 3.61e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 245 LAPLTYISLVGCSISIVASLITVLLHFHFRKQS-DSLTRIHMNLHASVLLLNIAFLLSPAFAMSPvPGSACTALAAALHY 323
Cdd:cd15258    1 LHILTFISYVGCGISAIFLAITILTYIAFRKLRrDYPSKIHMNLCAALLLLNLAFLLSSWIASFG-SDGLCIAVAVALHY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 324 ALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGPCTIPvfdsweNGTGFQNMSI 403
Cdd:cd15258   80 FLLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPITIP------NGEGFQNDSF 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 404 CWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADA-PSVRACHDTVTVLGLTVLLGTTWALAFFSFGVFLL 482
Cdd:cd15258  154 CWIRDPVVFYITVVGYFGLTFLFNMVMLATVLVQICRLREKAQAtPRKRALHDLLTLLGLTFLLGLTWGLAFFAWGPFNL 233
                        250       260       270
                 ....*....|....*....|....*....|....
gi 767989595 483 PQLFLFTILNSLYGFFLFLWFCSQRCRSEAEAKA 516
Cdd:cd15258  234 PFLYLFAIFNSLQGFFIFIWYCSMKENVRKQWRA 267
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
248-510 3.46e-54

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: 183.88  E-value: 3.46e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHF-HFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPvPGSACTALAAALHYALL 326
Cdd:cd15995    4 LTILTYVGCIISALASVFTIAFYLcSRRKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTG-SEAACRAGGMFLHFSLL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGPCTIPVFDSWEngtGFQNMSICWV 406
Cdd:cd15995   83 ACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHRSPE---KVTYATICWI 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAPSvrachDTVTVLGLTVLLGTTWALAFFSF--GVFLLPQ 484
Cdd:cd15995  160 TDSLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTHKWS-----HVLTLLGLSLVLGIPWALAFFSFasGTFQLVI 234
                        250       260
                 ....*....|....*....|....*.
gi 767989595 485 LFLFTILNSLYGFFLFLWFCSQRCRS 510
Cdd:cd15995  235 VYLFTIINSLQGFLIFLWYWSMVLQA 260
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
248-503 6.32e-52

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: 178.07  E-value: 6.32e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRK-----QSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPGsACTALAAALH 322
Cdd:cd15442    4 LVTISSAGCGVSMVFLIFTIILYFFLRFtyqkfKSEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHPG-LCKALGGVTH 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 323 YALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPAllVLLSLSVKSSVYGPCTIpvfDSWENGTgfqNMS 402
Cdd:cd15442   83 YFLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLCLVGWGFPA--LVVTITGSINSYGAYTI---MDMANRT---TLH 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 403 ICWVRSP--VVHSVLVMGYGGLTSLFNLVVL---AWALWTLRRLreRADAPSVRACHDTVTVLGLTVLLGTTWALAFFSF 477
Cdd:cd15442  155 LCWINSKhlTVHYITVCGYFGLTFLFNTVVLglvAWKIFHLQSA--TAGKEKCQAWKGGLTVLGLSCLLGVTWGLAFFTY 232
                        250       260
                 ....*....|....*....|....*.
gi 767989595 478 GVFLLPQLFLFTILNSLYGFFLFLWF 503
Cdd:cd15442  233 GSMSVPTVYIFALLNSLQGLFIFIWF 258
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
248-504 1.31e-41

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: 150.20  E-value: 1.31e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRK-QSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPGsACTALAAALHYALL 326
Cdd:cd15997    4 LTLITYLGCGISSIFLGITLVTYLAFEKlRRDYPSKILINLCTALLMLNLVFLLNSWLSSFNNYG-LCITVAAFLHYFLL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGpcTIPVFDSWENGTGFqnmsiCWV 406
Cdd:cd15997   83 ASFTWMGLEAVHMYFALVKVFNIYIPNYILKFCIAGWGIPAVVVALVLAINKDFYG--NELSSDSLHPSTPF-----CWI 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAPSVRA--CHDTVTVLGLTVLLGTTWALAFFSFGVFLLPQ 484
Cdd:cd15997  156 QDDVVFYISVVAYFCLIFLCNISMFITVLIQIRSMKAKKPSRNWKQgfLHDLKSVASLTFLLGLTWGFAFFAWGPVRIFF 235
                        250       260
                 ....*....|....*....|
gi 767989595 485 LFLFTILNSLYGFFLFLWFC 504
Cdd:cd15997  236 LYLFSICNTLQGFFIFVFHC 255
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
248-504 2.28e-37

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: 138.81  E-value: 2.28e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRK-QSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPGSACTALAAALHYALL 326
Cdd:cd15444    4 LTFITYIGCGLSAIFLSVTLVTYIAFEKiRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKDIVGLCISVAVFLHYFLL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGpctipvFDSWENGTGFQNMSICWV 406
Cdd:cd15444   84 VSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYG------LGSYGKSPNGSTDDFCWI 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAPSVR--ACHDTVTVLGLTVLLGTTWALAFFSFGVFLLPQ 484
Cdd:cd15444  158 NNNIVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRktSLQDLRSVAGITFLLGITWGFAFFAWGPVNLAF 237
                        250       260
                 ....*....|....*....|
gi 767989595 485 LFLFTILNSLYGFFLFLWFC 504
Cdd:cd15444  238 MYLFAIFNTLQGFFIFIFYC 257
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
248-504 6.44e-37

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: 136.93  E-value: 6.44e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRK-QSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALL 326
Cdd:cd15040    4 LSIITYIGCGLSLLGLLLTIITYILFRKlRKRKPTKILLNLCLALLLANLLFLFGINSTDNPV---LCTAVAALLHYFLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPAllvllslsvkssvyGPCTIPVFDSWENGTGfqNMSICWV 406
Cdd:cd15040   81 ASFMWMLVEALLLYLRLVKVFGTYPRHFILKYALIGWGLPL--------------IIVIITLAVDPDSYGN--SSGYCWL 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAP-------SVRAchdtvtVLGLTVLLGTTWALAFFSFGV 479
Cdd:cd15040  145 SNGNGLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKkrkktkaQLRA------AVSLFFLLGLTWIFGILAIFG 218
                        250       260
                 ....*....|....*....|....*
gi 767989595 480 FLLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15040  219 ARVVFQYLFAIFNSLQGFFIFIFHC 243
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
248-507 3.73e-35

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: 132.70  E-value: 3.73e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRK-QSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPGsACTALAAALHYALL 326
Cdd:cd15996    4 LTFITYIGCGISAIFSAATLLTYIAFEKlRRDYPSKILMNLSTALLFLNLVFLLDGWIASFEIDE-LCITVAVLLHFFLL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGPCTIPVFDSWENGTGFqnmsiCWV 406
Cdd:cd15996   83 ATFTWMGLEAIHMYIALVKVFNTYIRRYILKFCIIGWGLPALIVSIVLASTNDNYGYGYYGKDKDGQGGDEF-----CWI 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RSPVVHSVLVMGYGGLTSLFNlvvLAWALWTLRRLRERADAPSVRACHDTV-----TVLGLTVLLGTTWALAFFSFGVFL 481
Cdd:cd15996  158 KNPVVFYVTCAAYFGIMFLMN---VAMFIVVMVQICGRNGKRSNRTLREEIlrnlrSVVSLTFLLGMTWGFAFFAWGPVN 234
                        250       260
                 ....*....|....*....|....*.
gi 767989595 482 LPQLFLFTILNSLYGFFLFLWFCSQR 507
Cdd:cd15996  235 LAFMYLFTIFNSLQGLFIFVFHCALK 260
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
248-504 5.09e-34

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: 129.25  E-value: 5.09e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSpAFAMSPVPGSACTALAAALHYALLS 327
Cdd:cd13952    4 LSIITYIGCSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIG-QLLTSSDRPVLCKALAILLHYFLLA 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 328 CLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGPctipvfdswengTGFQNMSICWVR 407
Cdd:cd13952   83 SFFWMLVEAFDLYRTFVKVFGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGP------------SPGYGGEYCWLS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 408 SPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRlRERADAPSVRACHDTVTV---LGLTVLLGTTWALAFFSFGVFLLPQ 484
Cdd:cd13952  151 NGNALLWAFYGPVLLILLVNLVFFILTVRILLR-KLRETPKQSERKSDRKQLrayLKLFPLMGLTWIFGILAPFVGGSLV 229
                        250       260
                 ....*....|....*....|.
gi 767989595 485 L-FLFTILNSLYGFFLFLWFC 504
Cdd:cd13952  230 FwYLFDILNSLQGFFIFLIFC 250
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
247-499 4.48e-22

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: 95.42  E-value: 4.48e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595  247 PLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPGS-----ACTALAAAL 321
Cdd:pfam00002   3 SLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLDhcswvGCKVVAVFL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595  322 HYALLSCLTWMAIEGFNLYLLLGRVYNIYiRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNM 401
Cdd:pfam00002  83 HYFFLANFFWMLVEGLYLYTLLVEVFFSE-RKYFWWYLLIGWGVPALVVGIWAGVDPKGYG-----------------ED 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595  402 SICWVRS----------PVVHSVLVmgyggltslfNLVVLAWALWTL-RRLRERADAPSVR--ACHDTVTVLGLTVLLGT 468
Cdd:pfam00002 145 DGCWLSNenglwwiirgPILLIILV----------NFIIFINIVRILvQKLRETNMGKSDLkqYRRLAKSTLLLLPLLGI 214
                         250       260       270
                  ....*....|....*....|....*....|....
gi 767989595  469 TWALAFFSFG---VFLLPQLFLFTILNSLYGFFL 499
Cdd:pfam00002 215 TWVFGLFAFNpenTLRVVFLYLFLILNSFQGFFV 248
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
247-504 1.06e-20

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: 91.56  E-value: 1.06e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 247 PLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLspafAMSPVPGSA-CTALAAALHYAL 325
Cdd:cd15440    3 ALTFITYIGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLCLCLLIAEIVFLL----GIDQTENRTlCGVIAGLLHYFF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 326 LSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVlGWGAPALlvllslsvkssvygpctIPVFDSWENGTGFQNMSICW 405
Cdd:cd15440   79 LAAFSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLF-GYGLPAL-----------------IVAVSAGVDPTGYGTEDHCW 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 406 VRS----------PVvhsVLVMgyggltsLFNLVVLAWALWTLRRLRERADAPSVRACHDTVTV-----LGLTVLLGTTW 470
Cdd:cd15440  141 LSTengfiwsfvgPV---IVVL-------LANLVFLGMAIYVMCRHSSRSASKKDASKLKNIRGwlkgsIVLVVLLGLTW 210
                        250       260       270
                 ....*....|....*....|....*....|....
gi 767989595 471 ALAFFSFGVFLLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15440  211 TFGLLFINQESIVMAYIFTILNSLQGLFIFIFHC 244
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
245-511 4.95e-20

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: 89.69  E-value: 4.95e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 245 LAPLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYA 324
Cdd:cd15933    1 ERALSIISYIGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGNKV---ACKVVAILLHFF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 325 LLSCLTWMAIEGFNLYLLLGRVYNIYIRR--YVFklgvLGWGAPALLVLLSLSVKSSVYGPCTIpvfdSWENgtgFQNMS 402
Cdd:cd15933   78 FMAAFSWMLVEGLHLYLMIVKVFNYKSKMryYYF----IGWGLPAIIVAISLAILFDDYGSPNV----CWLS---LDDGL 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 403 IcWVRSPVVHSVLVMgyggltslfNLVVLAWALWTLRRLRERADAP----------SVRAchdtvtVLGLTVLLGTTWAL 472
Cdd:cd15933  147 I-WAFVGPVIFIITV---------NTVILILVVKITVSLSTNDAKKsqgtlaqiksTAKA------SVVLLPILGLTWLF 210
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 767989595 473 AFFSFGVFLLPQLFLFTILNSLYGFFLFLWFCsqRCRSE 511
Cdd:cd15933  211 GVLVVNSQTIVFQYIFVILNSLQGLMIFLFHC--VLNSE 247
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
248-506 1.35e-16

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: 79.47  E-value: 1.35e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALLS 327
Cdd:cd15252    4 LTRITQVGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFLAELVFLIGINTTTNKI---FCSVIAGLLHYFFLA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 328 CLTWMAIEGFNLYLLL-GRVYNIYIRRYVFKLgvLGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNMSICWV 406
Cdd:cd15252   81 AFAWMFIEGIQLYLMLvEVFENEGSRHKNFYI--FGYGSPAVIVGVSAALGYRYYG-----------------TTKVCWL 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLrrLRERADAPSVRACHDTVT-----VLGLTVLLGTTWALAFFSFGVFL 481
Cdd:cd15252  142 STENYFIWSFIGPATLIILLNLIFLGVAIYKM--FRHTAGLKPEVSCLENIRswargAIALLFLLGLTWIFGVLHINHAS 219
                        250       260
                 ....*....|....*....|....*
gi 767989595 482 LPQLFLFTILNSLYGFFLFLWFCSQ 506
Cdd:cd15252  220 VVMAYLFTVSNSLQGMFIFLFHCVL 244
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
247-503 1.19e-15

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: 77.61  E-value: 1.19e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 247 PLTYISLVGCSISIVASLITVLLHFHFRK-QSDSLTRIHMNLHASVLLLNIAFL----------------------LSPA 303
Cdd:cd15257    3 TLDIISTIGCVLSIAGLVITIIFHLHTRKlRKSSVTWVLLNLCSSLLLFNIIFTsgventnndyeistvpdretntVLLS 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 304 FAMSPVPGSACTALAAALHYALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSSVYGP 383
Cdd:cd15257   83 EEYVEPDTDVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQASAIGWGIPAVVVAITLGATYRFPTS 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 384 ctIPVFDswengTGFQNMSICWV---------RSPVVHSVLVMgyGGLTSLFNLVVLAW----ALWTLRRLRERADAPSV 450
Cdd:cd15257  163 --LPVFT-----RTYRQEEFCWLaaldknfdiKKPLLWGFLLP--VGLILITNVILFIMtsqkVLKKNNKKLTTKKRSYM 233
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767989595 451 RACHDTVTVlglTVLLGTTWALAFFSFGVFLLPQL---FLFTILNSLYGFFLFLWF 503
Cdd:cd15257  234 KKIYITVSV---AVVFGITWILGYLMLVNNDLSKLvfsYIFCITNTTQGVQIFILY 286
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
247-507 1.37e-13

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: 71.10  E-value: 1.37e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 247 PLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAfaMSPVPGSACTALAAALHYALL 326
Cdd:cd15039    3 ILGILTLIGLIISLVFLLLTLAVYALLPELRNLHGKCLMCLVLSLFVAYLLLLIGQL--LSSGDSTLCVALGILLHFFFL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLG----RVYNIYIRRYVFKLGVLGWGAPALLVLLSLSVKSsvygpctIPVFDSWENGTGFQNms 402
Cdd:cd15039   81 AAFFWLNVMSFDIWRTFRgkrsSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDF-------SPNTDSLRPGYGEGS-- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 403 iCWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAPSVRACHDTVTV---LGLTVLLGTTWALAFFSFGV 479
Cdd:cd15039  152 -CWISNPWALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKVQSRLRSDKQRFrlyLKLFVIMGVTWILEIISWFV 230
                        250       260
                 ....*....|....*....|....*....
gi 767989595 480 FLLPQL-FLFTILNSLYGFFLFLWFCSQR 507
Cdd:cd15039  231 GGSSVLwYIFDILNGLQGVFIFLIFVCKR 259
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
188-232 1.77e-13

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: 64.64  E-value: 1.77e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 767989595  188 TCVFWKEGARKqpWGGWSPEGCRTEQPSHSQVLCRCNHLTYFAVL 232
Cdd:pfam01825   2 QCVFWDFTNST--TGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
248-504 7.69e-13

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: 68.80  E-value: 7.69e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISI---VASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPgsaCTALAAALHYA 324
Cdd:cd15256    4 LSSITYVGCSLSIfclAITLVTFAVLSSVSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLP---CKIMAILLHFF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 325 LLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGVlGWGAPALLVLLSLSVKSSVYGPctipVFDSWengTGFQNMSIC 404
Cdd:cd15256   81 FLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGI-GWGSPLLICIISLTSALDSYGE----SDNCW---LSLENGAIW 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 405 WVRSPVVHsVLVMGYGGLTSLFNLVVLAWAlwtlRRLRERADAPSVRACHDTVTVLglTVLLGTTWALAFFSFGVFLLPQ 484
Cdd:cd15256  153 AFVAPALF-VIVVNIGILIAVTRVISRISA----DNYKVHGDANAFKLTAKAVAVL--LPILGSSWVFGVLAVNTHALVF 225
                        250       260
                 ....*....|....*....|
gi 767989595 485 LFLFTILNSLYGFFLFLWFC 504
Cdd:cd15256  226 QYMFAIFNSLQGFFIFLFHC 245
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
247-511 1.04e-12

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: 68.25  E-value: 1.04e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 247 PLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALL 326
Cdd:cd15438    3 PLTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQV---ACAVVAGLLHYFFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYNIYI--RRYVFklgVLGWGAPALlvllslsvkssvygpctIPVFDSWENGTGFQNMSIC 404
Cdd:cd15438   80 AAFCWMSLEGVELYLMVVQVFNTQSlkKRYLL---LIGYGVPLV-----------------IVAISAAVNSKGYGTQRHC 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 405 WVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRER--ADAPSVRACHD-TVTVLGLTVLLGTTWALAFFSFGVFL 481
Cdd:cd15438  140 WLSLERGFLWSFLGPVCLIILVNAIIFVITVWKLAEKFSSinPDMEKLRKIRAlTITAIAQLCILGCTWIFGFFQFSDST 219
                        250       260       270
                 ....*....|....*....|....*....|..
gi 767989595 482 LPQLFLFTILNSLYGFFLFLWFC--SQRCRSE 511
Cdd:cd15438  220 LVMSYLFTILNSLQGLFIFLLHCllSKQVREE 251
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
248-504 1.21e-12

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: 68.05  E-value: 1.21e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALLS 327
Cdd:cd16005    4 LDVITWVGILLSLVCLLICIFTFCFFRGLQSDRNTIHKNLCISLFVAELLFLIGINRTDQPI---ACAVFAALLHFFFLA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 328 CLTWMAIEGFNLYLLLGRVY-NIYIRRYVFKLgvLGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNMSICWV 406
Cdd:cd16005   81 AFTWMFLEGVQLYIMLVEVFeSEHSRRKYFYL--VGYGMPALIVAVSAAVDYRSYG-----------------TDKVCWL 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLrrLRERADAPSVRACHDTVT-----VLGLTVLLGTTWALAFFSFGVFL 481
Cdd:cd16005  142 RLDTYFIWSFIGPATLIIMLNVIFLGIALYKM--FHHTAILKPESGCLDNIKswvigAIALLCLLGLTWAFGLMYINEST 219
                        250       260
                 ....*....|....*....|...
gi 767989595 482 LPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd16005  220 VIMAYLFTIFNSLQGMFIFIFHC 242
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
185-237 6.57e-12

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: 60.09  E-value: 6.57e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 767989595   185 YTLTCVFWKEGArkqpwGGWSPEGCRTEQPSHSQVLCRCNHLTYFAVLMQLSP 237
Cdd:smart00303   1 FNPICVFWDESS-----GEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPP 48
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
247-504 8.16e-12

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: 65.64  E-value: 8.16e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 247 PLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALL 326
Cdd:cd15991    3 PLKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIGINQTENPF---VCTVVAILLHYFYM 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYNI---YIRRYVfklgVLGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNMSI 403
Cdd:cd15991   80 STFAWMFVEGLHIYRMLTEVRNIntgHMRFYY----VVGWGIPAIITGLAVGLDPQGYG-----------------NPDF 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 404 CWVRspvVHSVLVMGYGG---LTSLFNLVVLAWALWTLRRLRERADAPSvRACHDTVTVLGLTVLLGTTWALAFFSFGVF 480
Cdd:cd15991  139 CWLS---VQDTLIWSFAGpigIVVIINTVIFVLAAKASCGRRQRYFEKS-GVISMLRTAFLLLLLISATWLLGLMAVNSD 214
                        250       260
                 ....*....|....*....|....
gi 767989595 481 LLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15991  215 TLSFHYLFAIFSCLQGIFIFFFHC 238
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
247-504 1.49e-11

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: 64.67  E-value: 1.49e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 247 PLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALL 326
Cdd:cd15439    3 ALTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQLSLCLFLADLLFLVGIDRTDNKV---LCSIIAGFLHYLFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLL---LGRVYNIYIRRYVFKLGVL-GWGAPALLVLLSLSVKSSVYgpctipvfdswenGTGFQnms 402
Cdd:cd15439   80 ACFAWMFLEAVHLFLTvrnLKVVNYFSSHRFKKRFMYPvGYGLPAVIVAISAAVNPQGY-------------GTPKH--- 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 403 iCWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLR-RLRE-RADAPSVRACHD-TVTVLGLTVLLGTTWALAFFSFGV 479
Cdd:cd15439  144 -CWLSMEKGFIWSFLGPVCVIIVINLVLFCLTLWILReKLSSlNAEVSTLKNTRLlTFKAIAQLFILGCTWILGLFQVGP 222
                        250       260
                 ....*....|....*....|....*
gi 767989595 480 FLLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15439  223 VATVMAYLFTITNSLQGVFIFLVHC 247
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
243-505 3.63e-11

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: 63.66  E-value: 3.63e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 243 ELLapLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALH 322
Cdd:cd15436    1 ELL--LFVITWVGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFIAELLFLIGINRTQYTI---ACPIFAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 323 YALLSCLTWMAIEGFNLYLLLGRVY-NIYIRRYVFKLGvlGWGAPALLVLLSLSVKSSVYGPCTipvfdswengtgfqnm 401
Cdd:cd15436   76 FFFLAAFCWLCLEGVQLYLLLVEVFeSEYSRRKYFYLC--GYSFPALVVAVSAAIDYRSYGTEK---------------- 137
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 402 sICWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWtlRRLRERADAPSVRACHD-----TVTVLGLTVLLGTTWALAFFS 476
Cdd:cd15436  138 -ACWLRVDNYFIWSFIGPVTFVITLNLVFLVITLH--KMVSHSDLLKPDSSRLDnikswALGAIALLFLLGLTWSFGLMF 214
                        250       260
                 ....*....|....*....|....*....
gi 767989595 477 FGVFLLPQLFLFTILNSLYGFFLFLWFCS 505
Cdd:cd15436  215 INEESVVMAYLFTIFNAFQGVFIFIFHCA 243
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
248-504 7.82e-10

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: 59.84  E-value: 7.82e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALLS 327
Cdd:cd15931    4 LEWINRVGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSMSHTLFLAGIEYVENEL---ACTVMAGLLHYLFLA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 328 CLTWMAIEGFNLYLLLGRVYNI-YIRRYVFK---LGVLGWGAPAllvllslsvkssvygpcTIPVFDSWENGTGFQNMSI 403
Cdd:cd15931   81 SFVWMLLEALQLHLLVRRLTKVqVIQRDGLPrplLCLIGYGVPF-----------------LIVGVSALVYSDGYGEAKM 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 404 CWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLR-RLRE-RADAPSVRACHD-TVTVLGLTVLLGTTWALAFFSFGVF 480
Cdd:cd15931  144 CWLSQERGFNWSFLGPVIAIIGINWILFCATLWCLRqTLSNmNSDISQLKDTRLlTFKAVAQLFILGCTWVLGLFQTNPV 223
                        250       260
                 ....*....|....*....|....
gi 767989595 481 LLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15931  224 ALVFQYLFTILNSLQGAFLFLVHC 247
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
243-505 9.14e-10

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: 59.55  E-value: 9.14e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 243 ELLapLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALH 322
Cdd:cd16007    1 ELL--LSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLIGIDKTQYQI---ACPIFAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 323 YALLSCLTWMAIEGFNLYLLLGRVYNI-YIRRYVFKLGvlGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNM 401
Cdd:cd16007   76 FFFLAAFSWLCLEGVQLYLMLVEVFESeYSRKKYYYLC--GYCFPALVVGISAAIDYRSYG-----------------TE 136
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 402 SICWVRspvVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADA---PSVRACHDTVTVLG---LTVLLGTTWALAFF 475
Cdd:cd16007  137 KACWLR---VDNYFIWSFIGPVSFVIVVNLVFLMVTLHKMIRSSSVlkpDSSRLDNIKSWALGaitLLFLLGLTWAFGLL 213
                        250       260       270
                 ....*....|....*....|....*....|
gi 767989595 476 SFGVFLLPQLFLFTILNSLYGFFLFLWFCS 505
Cdd:cd16007  214 FINKESVVMAYLFTTFNAFQGMFIFIFHCA 243
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
248-504 3.02e-09

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: 57.96  E-value: 3.02e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALLS 327
Cdd:cd15437    4 LTRITQLGIIISLICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELIFLIGINMNANKL---FCSIIAGLLHYFFLA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 328 CLTWMAIEGFNLYLLLGRVynIYIRRYVFK-LGVLGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNMSICWV 406
Cdd:cd15437   81 AFAWMCIEGIHLYLIVVGV--IYNKGFLHKnFYIFGYGSPAVVVGISAALGYKYYG-----------------TTKVCWL 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RSPVVHSVLVMGYGGLTSLFNLvvLAWALWTLRRLRERADAPSVRACHDTVT-----VLGLTVLLGTTWAlaffsFGVFL 481
Cdd:cd15437  142 STENNFIWSFIGPACLIILVNL--LAFGVIIYKVFRHTAMLKPEVSCYENIRscargALALLFLLGATWI-----FGVLH 214
                        250       260
                 ....*....|....*....|....*...
gi 767989595 482 LPQ-----LFLFTILNSLYGFFLFLWFC 504
Cdd:cd15437  215 VVYgsvvtAYLFTISNAFQGMFIFIFLC 242
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
244-504 7.55e-09

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: 56.49  E-value: 7.55e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 244 LLAPLTYISLvgcSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPgsaCTALAAALHY 323
Cdd:cd15441    3 LLKIVTYIGI---GISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELLFLLGINQTENLFP---CKLIAILLHY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 324 ALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGvLGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNMSI 403
Cdd:cd15441   77 FYLSAFSWLLVESLHLYRMLTEPRDINHGHMRFYYL-LGYGIPAIIVGLSVGLRPDGYG-----------------NPDF 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 404 CWVRspvVHSVLVMGYGG---LTSLFNLVVLAWALWTLRRLRER-ADAPSVRAchDTVTVLGLTVLLGTTWALAFFSFGV 479
Cdd:cd15441  139 CWLS---VNETLIWSFAGpiaFVIVITLIIFILALRASCTLKRHvLEKASVRT--DLRSSFLLLPLLGATWVFGLLAVNE 213
                        250       260
                 ....*....|....*....|....*
gi 767989595 480 FLLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15441  214 DSELLHYLFAGLNFLQGLFIFLFYC 238
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
243-504 8.10e-08

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: 53.38  E-value: 8.10e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 243 ELLapLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMspvPGSACTALAAALH 322
Cdd:cd16006    1 ELL--LTVITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIGIDKTE---YKIACPIFAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 323 YALLSCLTWMAIEGFNLYLLLGRVY-NIYIRRYVFKLGvlGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNM 401
Cdd:cd16006   76 FFFLAAFAWMCLEGVQLYLMLVEVFeSEYSRKKYYYVA--GYLFPATVVGVSAAIDYKSYG-----------------TE 136
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 402 SICWVRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTLRRLRERADAPSVRACHDTVTVLG---LTVLLGTTWALAFFSFG 478
Cdd:cd16006  137 KACWLRVDNYFIWSFIGPVTFIILLNLIFLVITLCKMVKHSNTLKPDSSRLENIKSWVLGafaLLCLLGLTWSFGLLFIN 216
                        250       260
                 ....*....|....*....|....*.
gi 767989595 479 VFLLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd16006  217 EETIVMAYLFTIFNAFQGMFIFIFHC 242
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
247-504 1.52e-07

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: 52.70  E-value: 1.52e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 247 PLTYISLVGCSISIVASLITVLLHF----HFRKQSDSLTRiH---MNLHASVLLLNIAFLLSPAFAMSPVPGSACTALAA 319
Cdd:cd15932    3 ALDYITYVGLGISILSLVLCLIIEAlvwkSVTKNKTSYMR-HvclVNIALSLLIADIWFIIGAAISTPPNPSPACTAATF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 320 ALHYALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGV-LGWGAPALLvllslsvkssvygpcTIPVFDSWENGTGF 398
Cdd:cd15932   82 FIHFFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIAFsLGYGCPLII---------------AIITVAATAPQGGY 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 399 QNMSICWVRSPVVHSVLVMGYGGLT-SLFNLVVLAWALWTLRR--LRERADAPSVRACHDTV-TVLGLTVLLGTTWAlaf 474
Cdd:cd15932  147 TRKGVCWLNWDKTKALLAFVIPALAiVVVNFIILIVVIFKLLRpsVGERPSKDEKNALVQIGkSVAILTPLLGLTWG--- 223
                        250       260       270
                 ....*....|....*....|....*....|....
gi 767989595 475 FSFGVFLLPQ----LFLFTILNSLYGFFLFLWFC 504
Cdd:cd15932  224 FGLGTMIDPKslafHIIFAILNSFQGFFILVFGT 257
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
248-504 1.84e-07

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: 52.61  E-value: 1.84e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 248 LTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLS-----PAFAMSPVPGSA-------CT 315
Cdd:cd15041    4 VYYIYLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFLSFILRAVFWIIWdllvvYDRLTSSGVETVlmqnpvgCK 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 316 ALAAALHYALLSCLTWMAIEGFNLYLLLGRVyNIYIRRYVFKLGVLGWGAPAllvllslsVKSSVYGPCTIPVFDS--WE 393
Cdd:cd15041   84 LLSVLKRYFKSANYFWMLCEGLYLHRLIVVA-FFSEPSSLKLYYAIGWGLPL--------VIVVIWAIVRALLSNEscWI 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 394 NGTgfqNMSICWV-RSPVVHSVLVmgyggltslfNLVVLAWALWTL-RRLRER-ADAPS-----VRAchdtvtVLGLTVL 465
Cdd:cd15041  155 SYN---NGHYEWIlYGPNLLALLV----------NLFFLINILRILlTKLRSHpNAEPSnyrkaVKA------TLILIPL 215
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 767989595 466 LGTTWALAFFSF---GVFLLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15041  216 FGIQYLLTIYRPpdgSEGELVYEYFNAILNSSQGFFVAVIYC 257
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
251-504 9.25e-06

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: 47.41  E-value: 9.25e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 251 ISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFL-----LSPAFAMSPVPgsACTALAAALHYAL 325
Cdd:cd15264    7 IYYLGFSISLVALAVALIIFLYFRSLRCLRNNIHCNLIVTFILRNVTWFimqntLTEIHHQSNQW--VCRLIVTVYNYFQ 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 326 LSCLTWMAIEGFNLYLLLGRVYNI-YIRRYVFKlgVLGWGAPallvllslsvkssvygpctIPVFDSWENGTGFQNMSIC 404
Cdd:cd15264   85 VTNFFWMFVEGLYLHTMIVWAYSAdKIRFWYYI--VIGWCIP-------------------CPFVLAWAIVKLLYENEHC 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 405 W--VRSPVVHSVLVMGYGGLTSLFNLVVLAWALWTL-RRLRERADAPSVRACHDTVTVLGLTVLLGTTWALAFFSFGVFL 481
Cdd:cd15264  144 WlpKSENSYYDYIYQGPILLVLLINFIFLFNIVWVLiTKLRASNTLETIQYRKAVKATLVLLPLLGITYMLFFINPGDDK 223
                        250       260
                 ....*....|....*....|....*.
gi 767989595 482 LPQL-FLF--TILNSLYGFFLFLWFC 504
Cdd:cd15264  224 TSRLvFIYfnTFLQSFQGLFVAVFYC 249
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
249-367 1.47e-05

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: 46.59  E-value: 1.47e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 249 TYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPGS-ACTALAAALHYALLS 327
Cdd:cd15263    5 TTIYFIGYSLSLVALSLALWIFLYFKDLRCLRNTIHTNLMFTYILADLTWILTLTLQVSIGEDQkSCIILVVLLHYFHLT 84
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 767989595 328 CLTWMAIEGFNLYLLLGRVY---NIYIRRYVFklgvLGWGAPA 367
Cdd:cd15263   85 NFFWMFVEGLYLYMLVVETFsgeNIKLRVYAF----IGWGIPA 123
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
250-367 2.45e-04

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: 43.03  E-value: 2.45e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 250 YISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAM--------SPVpgsACTALAAAL 321
Cdd:cd15260    6 YVYIGGYSVSLIALIISLAIFFSFRSLRCTRITIHMNLFISFALNNLLWIVWYKLVVdnpevlleNPI---WCQALHVLL 82
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 767989595 322 HYALLSCLTWMAIEGFNLYLLLGRVYnIYIRRYVFKLGVLGWGAPA 367
Cdd:cd15260   83 QYFMVCNYFWMFCEGLYLHTVLVVAF-ISEKSLMRWFIAIGWGVPL 127
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
251-504 2.55e-04

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: 43.00  E-value: 2.55e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 251 ISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFL-----LSPAFAMSPVpgSACTALAAALHYAL 325
Cdd:cd15445    7 INYLGHCISLVALLVAFVLFLRLRSIRCLRNIIHWNLITAFILRNATWFvvqltMSPEVHQSNV--VWCRLVTAAYNYFH 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 326 LSCLTWMAIEGFNLYLLLGRVYNI-YIRRYVFKlgVLGWGAPallvllslsvkssvygpctIPVFDSWENGTGFQNMSIC 404
Cdd:cd15445   85 VTNFFWMFGEGCYLHTAIVLTYSTdKLRKWMFI--CIGWCIP-------------------FPIIVAWAIGKLYYDNEKC 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 405 WV--RSPVVHSVLVMGYGGLTSLFNLVVLAWALWTL-RRLRERADAPSVRACHDTVTVLGLTVLLGTTWALAFFSFG--- 478
Cdd:cd15445  144 WFgkRAGVYTDYIYQGPMILVLLINFIFLFNIVRILmTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGede 223
                        250       260
                 ....*....|....*....|....*.
gi 767989595 479 VFLLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15445  224 ISRIVFIYFNSFLESFQGFFVSVFYC 249
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
243-504 6.59e-04

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: 41.75  E-value: 6.59e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 243 ELLAPLTYISLvgcSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALH 322
Cdd:cd15993    2 ETLAIVTYSSV---SASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLGINRTENQF---LCTVVAILLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 323 YALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGvLGWGAPALLVLLSLSVkssvygpctipvfdsweNGTGFQNMS 402
Cdd:cd15993   76 YFFLSTFAWLFVQGLHIYRMQTEARNVNFGAMRFYYA-IGWGVPAIITGLAVGL-----------------DPEGYGNPD 137
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 403 ICWVRSpvvHSVLVMGYGGLTSLFNLVVLAWALWTLRRL-----RERADAPSVRACHDTVTVLgltVLLGTTWALAFFSF 477
Cdd:cd15993  138 FCWISI---HDKLVWSFAGPIVVVIVMNGVMFLLVARMScspgqKETKKTSVLMTLRSSFLLL---LLISATWLFGLLAV 211
                        250       260
                 ....*....|....*....|....*..
gi 767989595 478 GVFLLPQLFLFTILNSLYGFFLFLWFC 504
Cdd:cd15993  212 NNSVLAFHYLHAILCCLQGLAVLLLFC 238
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
254-366 8.24e-04

pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PACAP-R1) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), 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. 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. PACAP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level.


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 41.49  E-value: 8.24e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 254 VGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPGSAC---TALAAALHYALLSCLT 330
Cdd:cd15987   10 VGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQDSDHCfvsTVECKAVMVFFHYCVM 89
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 767989595 331 ----WMAIEGFNLYLLLGRVYnIYIRRYVFKLGVLGWGAP 366
Cdd:cd15987   90 snyfWLFIEGLYLFTLLVETF-FPERRYFYWYTIIGWGTP 128
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
254-367 2.22e-03

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: 40.11  E-value: 2.22e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 254 VGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMS-------PVPGSACTALAAALHYALL 326
Cdd:cd15930   10 VGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKDAVLFSsedvdhcFVSTVGCKASMVFFQYCVM 89
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYnIYIRRYVFKLGVLGWGAPA 367
Cdd:cd15930   90 ANFFWLLVEGLYLHTLLVISF-FSERRYFWWYVLIGWGAPT 129
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
247-501 4.84e-03

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: 39.03  E-value: 4.84e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 247 PLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVpgsACTALAAALHYALL 326
Cdd:cd15992    3 PLKTLTWSSVGVTLGFLLLTFLFLLCLRALRSNKTSIRKNGATALFLSELVFILGINQADNPF---ACTVIAILLHFFYL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 327 SCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLgVLGWGAPALLVLLSLSVKSSVYGpctipvfdswengtgfqNMSICWV 406
Cdd:cd15992   80 CTFSWLFLEGLHIYRMLSEVRDINYGPMRFYY-LIGWGVPAFITGLAVGLDPEGYG-----------------NPDFCWL 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 407 RspvVHSVLVMGYGG------LTSLFNLVVLAWALWTLRRLRERADAPSVRACHDTVTVLgltVLLGTTWALAFFSFGVF 480
Cdd:cd15992  142 S---IYDTLIWSFAGpvafavSMNVFLYILSSRASCSAQQQSFEKKKGPVSGLRTAFTVL---LLVSVTCLLALLSVNSD 215
                        250       260
                 ....*....|....*....|.
gi 767989595 481 LLPQLFLFTILNSLYGFFLFL 501
Cdd:cd15992  216 VILFHYLFAGFNCLQGPFIFL 236
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
245-367 7.95e-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: 38.18  E-value: 7.95e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 245 LAPLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPVPG------------- 311
Cdd:cd15929    1 LSSLQVMYTVGYSLSLAALVLALAILLGLRKLHCTRNYIHANLFASFILRALSVLVKDALLPRRYSQkgdqdlwstllsn 80
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 312 ---SACTALAAALHYALLSCLTWMAIEGFNLYLLLgrVYNIYIRRYVFKLGV-LGWGAPA 367
Cdd:cd15929   81 qasLGCRVAQVLMQYCVAANYYWLLVEGLYLHTLL--VLAVFSERSIFRLYLlLGWGAPV 138
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
253-367 9.45e-03

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: 38.01  E-value: 9.45e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767989595 253 LVGCSISIVASLITVLLHFHF-RKQSDSLTRIHMNLHASVLLLNIAFLLSPAFAMSPvpgSACTALAAALHYALLSCLTW 331
Cdd:cd15988    9 MIGCAVSCMALLILLAIYAAFwRFIRSERSIILLNFCLSILASNILILVGQSQTLSK---GVCTMTAAFLHFFFLSSFCW 85
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 767989595 332 MAIEGFNLYL-LLGRVYNIYIRRyvfKLGVLGWGAPA 367
Cdd:cd15988   86 VLTEAWQSYLaVIGRMRTRLVRK---RFLCLGWGLPA 119
 
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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