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Conserved domains on  [gi|530424522|ref|XP_005256303|]
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adhesion G-protein coupled receptor G1 isoform X2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
400-674 3.08e-156

seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.


The actual alignment was detected with superfamily member cd15995:

Pssm-ID: 475119  Cd Length: 269  Bit Score: 451.98  E-value: 3.08e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASA 479
Cdd:cd15995    1 KHYLTILTYVGCIISALASVFTIAFYLCSR------RKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGG 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 480 IFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAVHRTPEGVIYP 559
Cdd:cd15995   75 MFLHFSLLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHRSPEKVTYA 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 560 SMCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQLVV 639
Cdd:cd15995  155 TICWITDSLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTHKWSHVLTLLGLSLVLGIPWALAFFSFASGTFQLVI 234
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 530424522 640 LYLFSIITSFQGFLIFIWYWSMRLQARGGPSPLKS 674
Cdd:cd15995  235 VYLFTIINSLQGFLIFLWYWSMVLQARGGPSPLKS 269
PLL pfam18587
PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles ...
29-162 6.51e-89

PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. The N-terminal domain of GPR56 has low sequence identity and a fold that likely diverged from the PTX and LNS domains. It also has a conserved motif (HphiC91xxWxxxxG) that was identified among canonical PTX domains. Thus, it is termed the Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL) domain. Truncation-based analyses suggest that the regions of GPR56 responsible for binding TG2 and collagen III are within the PLL domain, most likely in the surface-exposed conserved patch. Furthermore, it is suggested that the conserved patch of the PLL domain mediates an essential function in CNS myelination.


:

Pssm-ID: 436599  Cd Length: 134  Bit Score: 273.77  E-value: 6.51e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522   29 REDFRFCSQRNQTHRSSLHYKPTPDLRISIENSEEALTVHAPFPAAHPASRSFPDPRGLYHFCLYWNRHAGRLHLLYGKR 108
Cdd:pfam18587   1 REDFRFCGQRNQTQNSSLIYEQTPELHISIENSEEALTIKAPFPPNPRASYSLPDPLGLYHFCLYWFRHAGTLHLRYGKQ 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530424522  109 DFLLSDKASSLLCFQHQEESLAQGPPLLATSVTSWWSPQNISLPSAASFTFSFH 162
Cdd:pfam18587  81 DFLLSDDASSLLCFRHQEESLSQGPPLLNVSYSSWWGPQNTSLPSASGYTFSFH 134
GAIN_A pfam18619
GPCR-Autoproteolysis-INducing (GAIN) subdomain A; GPR56 is a a cell-surface G protein-coupled ...
173-220 3.30e-27

GPCR-Autoproteolysis-INducing (GAIN) subdomain A; GPR56 is a a cell-surface G protein-coupled receptor (GPCR) which belongs to the adhesion G protein-coupled receptor (aGPCR) family, a large family of chimeric proteins that have both adhesion and signaling functions and play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. This entry represents GPCR-Autoproteolysis-INducing (GAIN) subdomain A, including PLL-GAIN linker (F161-D175) region.


:

Pssm-ID: 436625  Cd Length: 48  Bit Score: 104.09  E-value: 3.30e-27
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 530424522  173 SVDMCELKRDLQLLSQFLKHPQKASRRPSAAPASQQLQSLESKLTSVR 220
Cdd:pfam18619   1 SVDMCELKRDLQLLSQLLKHPQKASRRPSSTPASQQLQSLESKLTSVR 48
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
345-388 2.51e-15

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


:

Pssm-ID: 460350  Cd Length: 44  Bit Score: 70.03  E-value: 2.51e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 530424522  345 QCVFWveDPTLSSPGHWSSAGCETVR-RETQTSCFCNHLTYFAVL 388
Cdd:pfam01825   2 QCVFW--DFTNSTTGRWSTEGCTTVSlNDTHTVCSCNHLTSFAVL 44
 
Name Accession Description Interval E-value
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
400-674 3.08e-156

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: 451.98  E-value: 3.08e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASA 479
Cdd:cd15995    1 KHYLTILTYVGCIISALASVFTIAFYLCSR------RKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGG 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 480 IFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAVHRTPEGVIYP 559
Cdd:cd15995   75 MFLHFSLLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHRSPEKVTYA 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 560 SMCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQLVV 639
Cdd:cd15995  155 TICWITDSLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTHKWSHVLTLLGLSLVLGIPWALAFFSFASGTFQLVI 234
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 530424522 640 LYLFSIITSFQGFLIFIWYWSMRLQARGGPSPLKS 674
Cdd:cd15995  235 VYLFTIINSLQGFLIFLWYWSMVLQARGGPSPLKS 269
PLL pfam18587
PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles ...
29-162 6.51e-89

PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. The N-terminal domain of GPR56 has low sequence identity and a fold that likely diverged from the PTX and LNS domains. It also has a conserved motif (HphiC91xxWxxxxG) that was identified among canonical PTX domains. Thus, it is termed the Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL) domain. Truncation-based analyses suggest that the regions of GPR56 responsible for binding TG2 and collagen III are within the PLL domain, most likely in the surface-exposed conserved patch. Furthermore, it is suggested that the conserved patch of the PLL domain mediates an essential function in CNS myelination.


Pssm-ID: 436599  Cd Length: 134  Bit Score: 273.77  E-value: 6.51e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522   29 REDFRFCSQRNQTHRSSLHYKPTPDLRISIENSEEALTVHAPFPAAHPASRSFPDPRGLYHFCLYWNRHAGRLHLLYGKR 108
Cdd:pfam18587   1 REDFRFCGQRNQTQNSSLIYEQTPELHISIENSEEALTIKAPFPPNPRASYSLPDPLGLYHFCLYWFRHAGTLHLRYGKQ 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530424522  109 DFLLSDKASSLLCFQHQEESLAQGPPLLATSVTSWWSPQNISLPSAASFTFSFH 162
Cdd:pfam18587  81 DFLLSDDASSLLCFRHQEESLSQGPPLLNVSYSSWWGPQNTSLPSASGYTFSFH 134
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
403-654 8.12e-28

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: 112.76  E-value: 8.12e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522  403 LSLLSYVGCVVSALACLVTIAAYLCSRvPLPCRRkprdytIKVHMNLLLAVFLLDTSFLL------SEPVALTGSEAGCR 476
Cdd:pfam00002   4 LKVIYTVGYSLSLVALLLAIAIFLLFR-KLHCTR------NYIHLNLFASFILRALLFLVgdavlfNKQDLDHCSWVGCK 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522  477 ASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiilavhrtpegv 556
Cdd:pfam00002  77 VVAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERK-YFWWYLLIGWGVPALVVGIWAGVDPKGYG------------- 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522  557 iYPSMCWIRDSLVSYITNLGLFSLVFLFNMAMLaTMVVQIL--RLRPHTQKWSHVLTLLGLSLVLGL-------PWALIF 627
Cdd:pfam00002 143 -EDDGCWLSNENGLWWIIRGPILLIILVNFIIF-INIVRILvqKLRETNMGKSDLKQYRRLAKSTLLllpllgiTWVFGL 220
                         250       260
                  ....*....|....*....|....*...
gi 530424522  628 FSFASGTFQLVV-LYLFSIITSFQGFLI 654
Cdd:pfam00002 221 FAFNPENTLRVVfLYLFLILNSFQGFFV 248
GAIN_A pfam18619
GPCR-Autoproteolysis-INducing (GAIN) subdomain A; GPR56 is a a cell-surface G protein-coupled ...
173-220 3.30e-27

GPCR-Autoproteolysis-INducing (GAIN) subdomain A; GPR56 is a a cell-surface G protein-coupled receptor (GPCR) which belongs to the adhesion G protein-coupled receptor (aGPCR) family, a large family of chimeric proteins that have both adhesion and signaling functions and play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. This entry represents GPCR-Autoproteolysis-INducing (GAIN) subdomain A, including PLL-GAIN linker (F161-D175) region.


Pssm-ID: 436625  Cd Length: 48  Bit Score: 104.09  E-value: 3.30e-27
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 530424522  173 SVDMCELKRDLQLLSQFLKHPQKASRRPSAAPASQQLQSLESKLTSVR 220
Cdd:pfam18619   1 SVDMCELKRDLQLLSQLLKHPQKASRRPSSTPASQQLQSLESKLTSVR 48
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
345-388 2.51e-15

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


Pssm-ID: 460350  Cd Length: 44  Bit Score: 70.03  E-value: 2.51e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 530424522  345 QCVFWveDPTLSSPGHWSSAGCETVR-RETQTSCFCNHLTYFAVL 388
Cdd:pfam01825   2 QCVFW--DFTNSTTGRWSTEGCTTVSlNDTHTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
342-389 8.84e-11

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: 57.40  E-value: 8.84e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 530424522   342 VTLQCVFWVEdptlsSPGHWSSAGCETV-RRETQTSCFCNHLTYFAVLM 389
Cdd:smart00303   1 FNPICVFWDE-----SSGEWSTRGCELLeTNGTHTTCSCNHLTTFAVLM 44
 
Name Accession Description Interval E-value
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
400-674 3.08e-156

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: 451.98  E-value: 3.08e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASA 479
Cdd:cd15995    1 KHYLTILTYVGCIISALASVFTIAFYLCSR------RKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGG 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 480 IFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAVHRTPEGVIYP 559
Cdd:cd15995   75 MFLHFSLLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHRSPEKVTYA 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 560 SMCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQLVV 639
Cdd:cd15995  155 TICWITDSLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTHKWSHVLTLLGLSLVLGIPWALAFFSFASGTFQLVI 234
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 530424522 640 LYLFSIITSFQGFLIFIWYWSMRLQARGGPSPLKS 674
Cdd:cd15995  235 VYLFTIINSLQGFLIFLWYWSMVLQARGGPSPLKS 269
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
400-671 3.40e-121

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: 362.12  E-value: 3.40e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASA 479
Cdd:cd15258    1 LHILTFISYVGCGISAIFLAITILTYIAFR------KLRRDYPSKIHMNLCAALLLLNLAFLLSSWIASFGSDGLCIAVA 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 480 IFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAvhrTPEGVIYP 559
Cdd:cd15258   75 VALHYFLLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPITIP---NGEGFQND 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 560 SMCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQ------KWSHVLTLLGLSLVLGLPWALIFFSFasG 633
Cdd:cd15258  152 SFCWIRDPVVFYITVVGYFGLTFLFNMVMLATVLVQICRLREKAQatprkrALHDLLTLLGLTFLLGLTWGLAFFAW--G 229
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 530424522 634 TFQLVVLYLFSIITSFQGFLIFIWYWSMRLQARGGPSP 671
Cdd:cd15258  230 PFNLPFLYLFAIFNSLQGFFIFIWYCSMKENVRKQWRA 267
PLL pfam18587
PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles ...
29-162 6.51e-89

PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. The N-terminal domain of GPR56 has low sequence identity and a fold that likely diverged from the PTX and LNS domains. It also has a conserved motif (HphiC91xxWxxxxG) that was identified among canonical PTX domains. Thus, it is termed the Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL) domain. Truncation-based analyses suggest that the regions of GPR56 responsible for binding TG2 and collagen III are within the PLL domain, most likely in the surface-exposed conserved patch. Furthermore, it is suggested that the conserved patch of the PLL domain mediates an essential function in CNS myelination.


Pssm-ID: 436599  Cd Length: 134  Bit Score: 273.77  E-value: 6.51e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522   29 REDFRFCSQRNQTHRSSLHYKPTPDLRISIENSEEALTVHAPFPAAHPASRSFPDPRGLYHFCLYWNRHAGRLHLLYGKR 108
Cdd:pfam18587   1 REDFRFCGQRNQTQNSSLIYEQTPELHISIENSEEALTIKAPFPPNPRASYSLPDPLGLYHFCLYWFRHAGTLHLRYGKQ 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530424522  109 DFLLSDKASSLLCFQHQEESLAQGPPLLATSVTSWWSPQNISLPSAASFTFSFH 162
Cdd:pfam18587  81 DFLLSDDASSLLCFRHQEESLSQGPPLLNVSYSSWWGPQNTSLPSASGYTFSFH 134
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
403-668 7.50e-65

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: 215.39  E-value: 7.50e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFL 482
Cdd:cd15443    4 LTYISIVGCSISAAASLLTILLHFFSR------KQPKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQSTWLCRAAAALL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAvhrTPEGVIYPSMC 562
Cdd:cd15443   78 HYSLLCCLTWMAIEGFHLYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFKREAYGPHTIP---TGTGYQNASMC 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 563 WIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGL-----SLVLGLPWALIFFSFasGTFQL 637
Cdd:cd15443  155 WITSSKVHYVLVLGYAGLTSLFNLVVLAWVVRMLRRLRSRKQELGERARRDWVtvlglTCLLGTTWALAFFSF--GVFLI 232
                        250       260       270
                 ....*....|....*....|....*....|.
gi 530424522 638 VVLYLFSIITSFQGFLIFIWYWSMRLQARGG 668
Cdd:cd15443  233 PQLFLFTIINSLYGFFICLWYCTQRRRSDAS 263
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
403-666 1.18e-50

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: 176.61  E-value: 1.18e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPValTGSEAGCRASAIFL 482
Cdd:cd15040    4 LSIITYIGCGLSLLGLLLTIITYILFR------KLRKRKPTKILLNLCLALLLANLLFLFGINS--TDNPVLCTAVAALL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviYPSMC 562
Cdd:cd15040   76 HYFLLASFMWMLVEALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGN-------------SSGYC 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 563 WIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL------PWalIFFSFASGTFQ 636
Cdd:cd15040  143 WLSNGNGLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQLRAAVSLffllglTW--IFGILAIFGAR 220
                        250       260       270
                 ....*....|....*....|....*....|
gi 530424522 637 LVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd15040  221 VVFQYLFAIFNSLQGFFIFIFHCLRNKEVR 250
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
403-666 3.22e-47

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: 167.92  E-value: 3.22e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCsrvplpCRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFL 482
Cdd:cd15997    4 LTLITYLGCGISSIFLGITLVTYLA------FEKLRRDYPSKILINLCTALLMLNLVFLLNSWLSSFNNYGLCITVAAFL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiILAVHRTPEGviYPSMC 562
Cdd:cd15997   78 HYFLLASFTWMGLEAVHMYFALVKVFNIYIPNYILKFCIAGWGIPAVVVALVLAINKDFYG--NELSSDSLHP--STPFC 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 563 WIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQK--WSHVLTLLGLSLVLGL-----PWALIFFSFasGTF 635
Cdd:cd15997  154 WIQDDVVFYISVVAYFCLIFLCNISMFITVLIQIRSMKAKKPSrnWKQGFLHDLKSVASLTfllglTWGFAFFAW--GPV 231
                        250       260       270
                 ....*....|....*....|....*....|.
gi 530424522 636 QLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd15997  232 RIFFLYLFSICNTLQGFFIFVFHCLMKENVR 262
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
401-658 1.97e-46

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: 166.13  E-value: 1.97e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 401 HYLSLLSYVGCVVSALACLVTIAAYLCSRVPLPcRRKPRDyTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAI 480
Cdd:cd15442    2 QTLVTISSAGCGVSMVFLIFTIILYFFLRFTYQ-KFKSED-APKIHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKALGG 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 481 FLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVAlvDVDNYG--PIILAVHRTpegviY 558
Cdd:cd15442   80 VTHYFLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLCLVGWGFPALVVTITG--SINSYGayTIMDMANRT-----T 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 559 PSMCWIRDS--LVSYITNLGLFSLVFLFNMAMLATMVVQILRLR------PHTQKWSHVLTLLGLSLVLGLPWALIFFSF 630
Cdd:cd15442  153 LHLCWINSKhlTVHYITVCGYFGLTFLFNTVVLGLVAWKIFHLQsatagkEKCQAWKGGLTVLGLSCLLGVTWGLAFFTY 232
                        250       260
                 ....*....|....*....|....*...
gi 530424522 631 asGTFQLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15442  233 --GSMSVPTVYIFALLNSLQGLFIFIWF 258
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
403-658 1.12e-45

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: 163.54  E-value: 1.12e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvplpcrrKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFL 482
Cdd:cd13952    4 LSIITYIGCSLSLVGLLLTIITYLLFP-------KLRNLRGKILINLCLSLLLAQLLFLIGQLLTSSDRPVLCKALAILL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIilavhrtpeGVIYPSMC 562
Cdd:cd13952   77 HYFLLASFFWMLVEAFDLYRTFVKVFGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPS---------PGYGGEYC 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 563 WIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL-------PWALIFFSFASGtF 635
Cdd:cd13952  148 WLSNGNALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSDRKQLRAYLKlfplmglTWIFGILAPFVG-G 226
                        250       260
                 ....*....|....*....|...
gi 530424522 636 QLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd13952  227 SLVFWYLFDILNSLQGFFIFLIF 249
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
403-658 1.55e-41

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: 152.29  E-value: 1.55e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAG-CRASAIF 481
Cdd:cd15444    4 LTFITYIGCGLSAIFLSVTLVTYIAFE------KIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKDIVGlCISVAVF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 482 LHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiILAVHRTPEGVIyPSM 561
Cdd:cd15444   78 LHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYG--LGSYGKSPNGST-DDF 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 562 CWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLG-------LPWALIFFSFasGT 634
Cdd:cd15444  155 CWINNNIVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAgitfllgITWGFAFFAW--GP 232
                        250       260
                 ....*....|....*....|....
gi 530424522 635 FQLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15444  233 VNLAFMYLFAIFNTLQGFFIFIFY 256
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
403-662 1.29e-37

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: 141.18  E-value: 1.29e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFL 482
Cdd:cd15996    4 LTFITYIGCGISAIFSAATLLTYIAFE------KLRRDYPSKILMNLSTALLFLNLVFLLDGWIASFEIDELCITVAVLL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAVHRTPEGViyPSMC 562
Cdd:cd15996   78 HFFLLATFTWMGLEAIHMYIALVKVFNTYIRRYILKFCIIGWGLPALIVSIVLASTNDNYGYGYYGKDKDGQGG--DEFC 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 563 WIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQIL---------RLRPHTQKwsHVLTLLGLSLVLGLPWALIFFSFasG 633
Cdd:cd15996  156 WIKNPVVFYVTCAAYFGIMFLMNVAMFIVVMVQICgrngkrsnrTLREEILR--NLRSVVSLTFLLGMTWGFAFFAW--G 231
                        250       260
                 ....*....|....*....|....*....
gi 530424522 634 TFQLVVLYLFSIITSFQGFLIFIWYWSMR 662
Cdd:cd15996  232 PVNLAFMYLFTIFNSLQGLFIFVFHCALK 260
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
403-654 8.12e-28

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: 112.76  E-value: 8.12e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522  403 LSLLSYVGCVVSALACLVTIAAYLCSRvPLPCRRkprdytIKVHMNLLLAVFLLDTSFLL------SEPVALTGSEAGCR 476
Cdd:pfam00002   4 LKVIYTVGYSLSLVALLLAIAIFLLFR-KLHCTR------NYIHLNLFASFILRALLFLVgdavlfNKQDLDHCSWVGCK 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522  477 ASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiilavhrtpegv 556
Cdd:pfam00002  77 VVAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERK-YFWWYLLIGWGVPALVVGIWAGVDPKGYG------------- 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522  557 iYPSMCWIRDSLVSYITNLGLFSLVFLFNMAMLaTMVVQIL--RLRPHTQKWSHVLTLLGLSLVLGL-------PWALIF 627
Cdd:pfam00002 143 -EDDGCWLSNENGLWWIIRGPILLIILVNFIIF-INIVRILvqKLRETNMGKSDLKQYRRLAKSTLLllpllgiTWVFGL 220
                         250       260
                  ....*....|....*....|....*...
gi 530424522  628 FSFASGTFQLVV-LYLFSIITSFQGFLI 654
Cdd:pfam00002 221 FAFNPENTLRVVfLYLFLILNSFQGFFV 248
GAIN_A pfam18619
GPCR-Autoproteolysis-INducing (GAIN) subdomain A; GPR56 is a a cell-surface G protein-coupled ...
173-220 3.30e-27

GPCR-Autoproteolysis-INducing (GAIN) subdomain A; GPR56 is a a cell-surface G protein-coupled receptor (GPCR) which belongs to the adhesion G protein-coupled receptor (aGPCR) family, a large family of chimeric proteins that have both adhesion and signaling functions and play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. This entry represents GPCR-Autoproteolysis-INducing (GAIN) subdomain A, including PLL-GAIN linker (F161-D175) region.


Pssm-ID: 436625  Cd Length: 48  Bit Score: 104.09  E-value: 3.30e-27
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 530424522  173 SVDMCELKRDLQLLSQFLKHPQKASRRPSAAPASQQLQSLESKLTSVR 220
Cdd:pfam18619   1 SVDMCELKRDLQLLSQLLKHPQKASRRPSSTPASQQLQSLESKLTSVR 48
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
403-658 4.42e-26

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: 107.80  E-value: 4.42e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRVPlpcrrkpRDYTIKVHMNLLLAVFLLDTSFLLSEpvALTGSEAGCRASAIFL 482
Cdd:cd15933    4 LSIISYIGCGISIACLALTLIIFLVLRVL-------SSDRFQIHKNLCVALLLAQILLLAGE--WAEGNKVACKVVAILL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTyvpGYLLKL-SAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSM 561
Cdd:cd15933   75 HFFFMAAFSWMLVEGLHLYLMIVKVFNY---KSKMRYyYFIGWGLPAIIVAISLAILFDDYGS--------------PNV 137
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 562 CW--IRDSLVSYITNLGLFslVFLFNMAMLA-----TMVVQILRLRPHTQKWShVLTLLGLSLVLGLP-----WALIFFS 629
Cdd:cd15933  138 CWlsLDDGLIWAFVGPVIF--IITVNTVILIlvvkiTVSLSTNDAKKSQGTLA-QIKSTAKASVVLLPilgltWLFGVLV 214
                        250       260
                 ....*....|....*....|....*....
gi 530424522 630 FASGTfqLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15933  215 VNSQT--IVFQYIFVILNSLQGLMIFLFH 241
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
403-656 5.38e-23

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: 98.87  E-value: 5.38e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvPLPCRRkprdytIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15440    4 LTFITYIGCIISIVCLLLAFITFTCFR-NLQCDR------NTIHKNLCLCLLIAEIVFLLG--IDQTENRTLCGVIAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVF---GTYVPGYLLklsaMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyP 559
Cdd:cd15440   75 HYFFLAAFSWMLLEGFQLYVMLVEVFepeKSRIKWYYL----FGYGLPALIVAVSAGVDPTGYGT--------------E 136
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 560 SMCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLG----------LPWALIFFS 629
Cdd:cd15440  137 DHCWLSTENGFIWSFVGPVIVVLLANLVFLGMAIYVMCRHSSRSASKKDASKLKNIRGWLKgsivlvvllgLTWTFGLLF 216
                        250       260
                 ....*....|....*....|....*..
gi 530424522 630 FASGTfqLVVLYLFSIITSFQGFLIFI 656
Cdd:cd15440  217 INQES--IVMAYIFTILNSLQGLFIFI 241
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
403-658 3.90e-18

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: 84.97  E-value: 3.90e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvPLPCRRkprdytIKVHMNLLLA-------------VFLLDTSFLLSEPVALT 469
Cdd:cd15041    4 VYYIYLVGYSLSLVALLPAIVIFLYFR-SLRCTR------IRLHINLFLSfilravfwiiwdlLVVYDRLTSSGVETVLM 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 470 GSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFgTYVPGYLLKLSAMGWGFPIFLVTLVAlvdvdnygpIILAV 549
Cdd:cd15041   77 QNPVGCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAF-FSEPSSLKLYYAIGWGLPLVIVVIWA---------IVRAL 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 550 HRTpegviypSMCWIRDSLVSY-----ITNLG--LFSLVFLFNmamlatmVVQIL--RLRPHTQKWSHVLTLLGLSLVLG 620
Cdd:cd15041  147 LSN-------ESCWISYNNGHYewilyGPNLLalLVNLFFLIN-------ILRILltKLRSHPNAEPSNYRKAVKATLIL 212
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 530424522 621 LP-----WALIFFSFASG-TFQLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15041  213 IPlfgiqYLLTIYRPPDGsEGELVYEYFNAILNSSQGFFVAVIY 256
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
403-666 4.61e-18

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: 84.43  E-value: 4.61e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15438    4 LTLITKVGLSVSLFCLFLCILTFLFCR-SIRGTRN------TIHLHLCLSLFLAHLIFLLG--INNTNNQVACAVVAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYV--PGYLLklsAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPS 560
Cdd:cd15438   75 HYFFLAAFCWMSLEGVELYLMVVQVFNTQSlkKRYLL---LIGYGVPLVIVAISAAVNSKGYGT--------------QR 137
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 561 MCWI---RDSLVSYitnLGLFSLVFLFNMAMLATMVVQILR----LRPHTQKWSHVLTLLGLSLVLGL----PWALIFFS 629
Cdd:cd15438  138 HCWLsleRGFLWSF---LGPVCLIILVNAIIFVITVWKLAEkfssINPDMEKLRKIRALTITAIAQLCilgcTWIFGFFQ 214
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 530424522 630 FASGTfqLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd15438  215 FSDST--LVMSYLFTILNSLQGLFIFLLHCLLSKQVR 249
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
403-662 9.16e-18

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: 83.82  E-value: 9.16e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSaLACLVTIAAYLCSRVPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd16007    4 LSVITWVGIVIS-LVCLAICISTFCFLRGLQTDRN------TIHKNLCINLFLAELLFLIG--IDKTQYQIACPIFAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGT--------YVPGYLlklsamgwgFPIFLVTLVALVDVDNYGPiilavhrtpe 554
Cdd:cd16007   75 HFFFLAAFSWLCLEGVQLYLMLVEVFESeysrkkyyYLCGYC---------FPALVVGISAAIDYRSYGT---------- 135
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 555 gviyPSMCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHTQK------WSHVLTLLGLSLVLGLPWA 624
Cdd:cd16007  136 ----EKACWLRVDNYFIWSFIGPVSFVIVVNLVFLMVTLHKMIRsssvLKPDSSRldniksWALGAITLLFLLGLTWAFG 211
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 530424522 625 LIFFSFASgtfqLVVLYLFSIITSFQGFLIFIWYWSMR 662
Cdd:cd16007  212 LLFINKES----VVMAYLFTTFNAFQGMFIFIFHCALQ 245
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
402-656 1.28e-17

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: 83.43  E-value: 1.28e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 402 YLSLLSYVGCVVSALACLVTIAAYLCsrvpLPCRRKPRDYTIkvhMNLLLAVFLLDTSFLLSePVALTGSEAGCRASAIF 481
Cdd:cd15039    3 ILGILTLIGLIISLVFLLLTLAVYAL----LPELRNLHGKCL---MCLVLSLFVAYLLLLIG-QLLSSGDSTLCVALGIL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 482 LHFSLLTCLSWMGLEGYNLYRlvveVFGTYVPGY--------LLKLSAMGWGFPIFLVTLVALVD-VDNYGPIILAVhrt 552
Cdd:cd15039   75 LHFFFLAAFFWLNVMSFDIWR----TFRGKRSSSsrskerkrFLRYSLYAWGVPLLLVAVTIIVDfSPNTDSLRPGY--- 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 553 peGVIYpsmCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL--------PWA 624
Cdd:cd15039  148 --GEGS---CWISNPWALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKVQSRLRSDKQRFRLYLklfvimgvTWI 222
                        250       260       270
                 ....*....|....*....|....*....|..
gi 530424522 625 LIFFSFASGTFQlVVLYLFSIITSFQGFLIFI 656
Cdd:cd15039  223 LEIISWFVGGSS-VLWYIFDILNGLQGVFIFL 253
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
345-388 2.51e-15

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


Pssm-ID: 460350  Cd Length: 44  Bit Score: 70.03  E-value: 2.51e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 530424522  345 QCVFWveDPTLSSPGHWSSAGCETVR-RETQTSCFCNHLTYFAVL 388
Cdd:pfam01825   2 QCVFW--DFTNSTTGRWSTEGCTTVSlNDTHTVCSCNHLTSFAVL 44
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
403-666 4.32e-15

orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR133 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR144. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the Gs protein, leading to activation of adenylyl cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 75.73  E-value: 4.32e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCsrvpLPCRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15256    4 LSSITYVGCSLSIFCLAITLVTFAV----LSSVSTIRNQRYHIHANLSFAVLVAQILLLIS--FRFEPGTLPCKIMAILL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLkLSAMGWGFPIFLVTLVALVDVDNYGPIilavhrtpegviypSMC 562
Cdd:cd15256   78 HFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFY-YYGIGWGSPLLICIISLTSALDSYGES--------------DNC 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 563 W--IRDSLVSYITNLGLFslVFLFNMAMLATMVVQILRLRPHTQKW---SHVLTLLGLSLVLGLPW---ALIFFSFASGT 634
Cdd:cd15256  143 WlsLENGAIWAFVAPALF--VIVVNIGILIAVTRVISRISADNYKVhgdANAFKLTAKAVAVLLPIlgsSWVFGVLAVNT 220
                        250       260       270
                 ....*....|....*....|....*....|..
gi 530424522 635 FQLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd15256  221 HALVFQYMFAIFNSLQGFFIFLFHCLLNSEVR 252
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
403-666 4.54e-15

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: 75.84  E-value: 4.54e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCsrvplpCRrKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15439    4 LTVITYVGLIISLLCLFLAILTFLL------CR-SIRNTSTSLHLQLSLCLFLADLLFLVG--IDRTDNKVLCSIIAGFL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLV-----VEVFGTYVPGYLLkLSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegvi 557
Cdd:cd15439   75 HYLFLACFAWMFLEAVHLFLTVrnlkvVNYFSSHRFKKRF-MYPVGYGLPAVIVAISAAVNPQGYGT------------- 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 558 yPSMCWIRDSL-----------VSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTqkwSHVLTLLGLSLVLGLPWALI 626
Cdd:cd15439  141 -PKHCWLSMEKgfiwsflgpvcVIIVINLVLFCLTLWILREKLSSLNAEVSTLKNTR---LLTFKAIAQLFILGCTWILG 216
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 530424522 627 FFSFASGTfqLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd15439  217 LFQVGPVA--TVMAYLFTITNSLQGVFIFLVHCLLNRQVR 254
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
403-658 1.70e-14

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: 73.82  E-value: 1.70e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSaLACLVtiAAYLCsrvpLPCRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15441    4 LKIVTYIGIGIS-LVLLV--IAFLV----LSCLRGLQSNSNSIHKNLVACLLLAELLFLLG--INQTENLFPCKLIAILL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEV-FGTYvpGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSM 561
Cdd:cd15441   75 HYFYLSAFSWLLVESLHLYRMLTEPrDINH--GHMRFYYLLGYGIPAIIVGLSVGLRPDGYGN--------------PDF 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 562 CWIrdslvsYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQLVVL- 640
Cdd:cd15441  139 CWL------SVNETLIWSFAGPIAFVIVITLIIFILALRASCTLKRHVLEKASVRTDLRSSFLLLPLLGATWVFGLLAVn 212
                        250       260
                 ....*....|....*....|....*
gi 530424522 641 -------YLFSIITSFQGFLIFIWY 658
Cdd:cd15441  213 edsellhYLFAGLNFLQGLFIFLFY 237
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
402-656 2.74e-13

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: 70.62  E-value: 2.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 402 YLSLLSYVGCVVSALACLVTIAAYLCsrvplpCRRKPRDYTIkVHMNLLLAVFLLDTSFLLSEpvALTGSEAGCRASAIF 481
Cdd:cd15931    3 FLEWINRVGVIVSLFCLGLAIFTFLL------CRWIPKINTT-AHLHLCLCLSMSHTLFLAGI--EYVENELACTVMAGL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 482 LHFSLLTCLSWMGLEGYNLYRLVVEVF-GTYVPGYLLK---LSAMGWGFPIFLVTLVALVDVDNYGpiilavhrtpegvi 557
Cdd:cd15931   74 LHYLFLASFVWMLLEALQLHLLVRRLTkVQVIQRDGLPrplLCLIGYGVPFLIVGVSALVYSDGYG-------------- 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 558 YPSMCWIRDSLVSYITNLGLFSLVFLFNmAMLATMVVQILR-----LRPH--TQKWSHVLTLLGLSLVLGLPWALIFFSF 630
Cdd:cd15931  140 EAKMCWLSQERGFNWSFLGPVIAIIGIN-WILFCATLWCLRqtlsnMNSDisQLKDTRLLTFKAVAQLFILGCTWVLGLF 218
                        250       260
                 ....*....|....*....|....*.
gi 530424522 631 ASGTFQLVVLYLFSIITSFQGFLIFI 656
Cdd:cd15931  219 QTNPVALVFQYLFTILNSLQGAFLFL 244
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
403-658 4.54e-13

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: 69.84  E-value: 4.54e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSaLACLVTIAAYLCSRVPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15252    4 LTRITQVGIIIS-LVCLAICIFTFWFFRGLQSDRT------TIHKNLCISLFLAELVFLIG--INTTTNKIFCSVIAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFgtYVPGYLLK-LSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSM 561
Cdd:cd15252   75 HYFFLAAFAWMFIEGIQLYLMLVEVF--ENEGSRHKnFYIFGYGSPAVIVGVSAALGYRYYGT--------------TKV 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 562 CWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRP------HTQKWSHVLTLLGLSLVLGLPWALIFFSFA 631
Cdd:cd15252  139 CWLSTENYFIWSFIGPATLIILLNLIFLGVAIYKMFRhtagLKPevscleNIRSWARGAIALLFLLGLTWIFGVLHINHA 218
                        250       260
                 ....*....|....*....|....*..
gi 530424522 632 SgtfqLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15252  219 S----VVMAYLFTVSNSLQGMFIFLFH 241
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
403-666 4.89e-13

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: 69.56  E-value: 4.89e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSaLACLVTIAAYLCSRVPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd16006    4 LTVITWVGIVIS-LVCLAICIFTFCFFRGLQSDRN------TIHKNLCINLFIAEFIFLIG--IDKTEYKIACPIFAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGT--------YVPGYLlklsamgwgFPIFLVTLVALVDVDNYGPiilavhrtpe 554
Cdd:cd16006   75 HFFFLAAFAWMCLEGVQLYLMLVEVFESeysrkkyyYVAGYL---------FPATVVGVSAAIDYKSYGT---------- 135
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 555 gviyPSMCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHTQK------WSHVLTLLGLSLVLGLPWA 624
Cdd:cd16006  136 ----EKACWLRVDNYFIWSFIGPVTFIILLNLIFLVITLCKMVKhsntLKPDSSRleniksWVLGAFALLCLLGLTWSFG 211
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 530424522 625 LIFFSFASgtfqLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd16006  212 LLFINEET----IVMAYLFTIFNAFQGMFIFIFHCALQKKVR 249
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
403-666 6.79e-13

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: 69.05  E-value: 6.79e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSaLACLVTIAAYLCsrvplpCRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15436    4 LFVITWVGIVIS-LVCLLICIFTFC------FFRGLQTDRNTIHKNLCINLFIAELLFLIG--INRTQYTIACPIFAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVF-GTYVPGYLLKLSamGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSM 561
Cdd:cd15436   75 HFFFLAAFCWLCLEGVQLYLLLVEVFeSEYSRRKYFYLC--GYSFPALVVAVSAAIDYRSYGT--------------EKA 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 562 CWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHTQK------WSHVLTLLGLSLVLGLPWALIFFSFA 631
Cdd:cd15436  139 CWLRVDNYFIWSFIGPVTFVITLNLVFLVITLHKMVShsdlLKPDSSRldniksWALGAIALLFLLGLTWSFGLMFINEE 218
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 530424522 632 SgtfqLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd15436  219 S----VVMAYLFTIFNAFQGVFIFIFHCALQKKVR 249
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
403-658 2.45e-12

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: 68.36  E-value: 2.45e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRVplpcRRKPRDYTIKVHMNLLLAVFLL---------------------DTSFL 461
Cdd:cd15257    4 LDIISTIGCVLSIAGLVITIIFHLHTRK----LRKSSVTWVLLNLCSSLLLFNIiftsgventnndyeistvpdrETNTV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 462 LSEPVALTGSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLV--TLVALVDV 539
Cdd:cd15257   80 LLSEEYVEPDTDVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQASAIGWGIPAVVVaiTLGATYRF 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 540 DNYGPIILAVHRTPEgviypsMCWIRDSLVSYITNLGLF-------SLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTL 612
Cdd:cd15257  160 PTSLPVFTRTYRQEE------FCWLAALDKNFDIKKPLLwgfllpvGLILITNVILFIMTSQKVLKKNNKKLTTKKRSYM 233
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530424522 613 LGLSLVLGL------PWALIFFSFA-SGTFQLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15257  234 KKIYITVSVavvfgiTWILGYLMLVnNDLSKLVFSYIFCITNTTQGVQIFILY 286
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
408-666 1.54e-11

orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group III adhesion GPCRs include orphan GPR123, GPR124, GPR125, and their closely related proteins. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 also interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Furthermore, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl.


Pssm-ID: 320387 [Multi-domain]  Cd Length: 260  Bit Score: 65.09  E-value: 1.54e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 408 YVGCVVSALACLVTIAAYLCSRVPLPCRRKPRdytikvHM--NLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFS 485
Cdd:cd15259    9 YAGAALCLLCLLATIITYIVFHRLIRISRKGR------HMlvNLCLHLLLTCVVFVGG--INRTANQLVCQAVGILLHYS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 486 LLTCLSWMGLEGYNLYRLVVEV--------FGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiilavhrtpegvi 557
Cdd:cd15259   81 TLCTLLWVGVTARNMYKQVTKTakppqdedQPPRPPKPMLRFYLIGWGIPLIICGITAAVNLDNYS-------------- 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 558 YPSMCWIRDSlvsyiTNLGLF----SLVFLFNMAMLATMVVQIlrLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASG 633
Cdd:cd15259  147 TYDYCWLAWD-----PSLGAFygpaALIVLVNCIYFLRIYCQL--KGAPVSFQSQLRGAVITLFLYVAMWACGALAVSQR 219
                        250       260       270
                 ....*....|....*....|....*....|....
gi 530424522 634 TF-QLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd15259  220 YFlDLVFSCLYGATCSSLGLFVLIHHCLSREDVR 253
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
342-389 8.84e-11

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: 57.40  E-value: 8.84e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 530424522   342 VTLQCVFWVEdptlsSPGHWSSAGCETV-RRETQTSCFCNHLTYFAVLM 389
Cdd:smart00303   1 FNPICVFWDE-----SSGEWSTRGCELLeTNGTHTTCSCNHLTTFAVLM 44
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
403-666 1.32e-10

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: 62.27  E-value: 1.32e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSaLACLVTIAAYLCSRVPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd16005    4 LDVITWVGILLS-LVCLLICIFTFCFFRGLQSDRN------TIHKNLCISLFVAELLFLIG--INRTDQPIACAVFAALL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYvPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMC 562
Cdd:cd16005   75 HFFFLAAFTWMFLEGVQLYIMLVEVFESE-HSRRKYFYLVGYGMPALIVAVSAAVDYRSYGT--------------DKVC 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 563 WIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHT------QKWSHVLTLLGLSLVLGLPWALIFFSFAS 632
Cdd:cd16005  140 WLRLDTYFIWSFIGPATLIIMLNVIFLGIALYKMFHhtaiLKPESgcldniKSWVIGAIALLCLLGLTWAFGLMYINEST 219
                        250       260       270
                 ....*....|....*....|....*....|....
gi 530424522 633 gtfqLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd16005  220 ----VIMAYLFTIFNSLQGMFIFIFHCVLQKKVR 249
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
403-658 2.06e-10

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: 61.79  E-value: 2.06e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIaaylcsrVPLPCRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15991    4 LKIITYTTVSLSLVALLITF-------ILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIG--INQTENPFVCTVVAILL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVpGYLLKLSAMGWGFPIFLVTlvalvdvdnygpiiLAVHRTPEGVIYPSMC 562
Cdd:cd15991   75 HYFYMSTFAWMFVEGLHIYRMLTEVRNINT-GHMRFYYVVGWGIPAIITG--------------LAVGLDPQGYGNPDFC 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 563 W--IRDSLVSYITnlGLFSLVFLFNMAMLATMVVQILRLRPHTQK----WSHVLTLLGLSLVLGLPWALIFFSFASGTfq 636
Cdd:cd15991  140 WlsVQDTLIWSFA--GPIGIVVIINTVIFVLAAKASCGRRQRYFEksgvISMLRTAFLLLLLISATWLLGLMAVNSDT-- 215
                        250       260
                 ....*....|....*....|..
gi 530424522 637 LVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15991  216 LSFHYLFAIFSCLQGIFIFFFH 237
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
404-600 1.00e-09

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: 60.08  E-value: 1.00e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 404 SLLSYVGCVVSALACLVTIAAYLCSRvPLPCRRKprdyTIkvHMNLLLAVFLLDTSFLLSEPVAL--TGSEAGCRASAIF 481
Cdd:cd15263    5 TTIYFIGYSLSLVALSLALWIFLYFK-DLRCLRN----TI--HTNLMFTYILADLTWILTLTLQVsiGEDQKSCIILVVL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 482 LHFSLLTCLSWMGLEGYNLYRLVVEVFGtyvpGYLLKLSA---MGWGFPIFLVTLVALvdVDNYGPIilAVHRTPEGVIY 558
Cdd:cd15263   78 LHYFHLTNFFWMFVEGLYLYMLVVETFS----GENIKLRVyafIGWGIPAVVIVIWAI--VKALAPT--APNTALDPNGL 149
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 530424522 559 PSMC-WIRDSLVSYITNlGLFSLVFLFNMAML-ATMVVQILRLR 600
Cdd:cd15263  150 LKHCpWMAEHIVDWIFQ-GPAILVLAVNLVFLvRIMWVLITKLR 192
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
403-542 3.62e-09

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR144 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR133. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the Gs protein, leading to activation of adenylyl cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320383 [Multi-domain]  Cd Length: 263  Bit Score: 58.32  E-value: 3.62e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRVPLPCRrkprdytIKVHMNLLLAVFLLDTSFLLSEPVAltGSEAGCRASAIFL 482
Cdd:cd15255    4 LRTLSFIGCGVSLCALIVTFILFLAVGVPKSER-------TTVHKNLIFALAAAEFLLMFSEWAK--GNQVACWAVTALL 74
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVfgTYVPGYLLKL-SAMGWGFPIFLVTLVALVDVDNY 542
Cdd:cd15255   75 HLFFLAAFSWMLVEGLLLWSKVVAV--NMSEDRRMKFyYVTGWGLPVVIVAVTLATSFNKY 133
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
445-657 5.06e-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: 57.58  E-value: 5.06e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 445 VHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFgtYVPGYLLK-LSAMG 523
Cdd:cd15437   39 IHKNLCCSLFLAELIFLIG--INMNANKLFCSIIAGLLHYFFLAAFAWMCIEGIHLYLIVVGVI--YNKGFLHKnFYIFG 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 524 WGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILR----L 599
Cdd:cd15437  115 YGSPAVVVGISAALGYKYYGT--------------TKVCWLSTENNFIWSFIGPACLIILVNLLAFGVIIYKVFRhtamL 180
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530424522 600 RPHTQKWSHVLTLLGLSLvlglpwALIFFSFASGTF--------QLVVLYLFSIITSFQGFLIFIW 657
Cdd:cd15437  181 KPEVSCYENIRSCARGAL------ALLFLLGATWIFgvlhvvygSVVTAYLFTISNAFQGMFIFIF 240
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
420-658 6.17e-09

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: 57.52  E-value: 6.17e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 420 VTIAAYLCSRVPLPCRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLTCLSWMGLEGYN 499
Cdd:cd15992   14 VTLGFLLLTFLFLLCLRALRSNKTSIRKNGATALFLSELVFILG--INQADNPFACTVIAILLHFFYLCTFSWLFLEGLH 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 500 LYRLVVEVFG-TYVPGYLLKLsaMGWGFPIFLVTlvalvdvdnygpiiLAVHRTPEGVIYPSMCW--IRDSLVSYITNLG 576
Cdd:cd15992   92 IYRMLSEVRDiNYGPMRFYYL--IGWGVPAFITG--------------LAVGLDPEGYGNPDFCWlsIYDTLIWSFAGPV 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 577 LFSL---VFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTfqLVVLYLFSIITSFQGFL 653
Cdd:cd15992  156 AFAVsmnVFLYILSSRASCSAQQQSFEKKKGPVSGLRTAFTVLLLVSVTCLLALLSVNSDV--ILFHYLFAGFNCLQGPF 233

                 ....*
gi 530424522 654 IFIWY 658
Cdd:cd15992  234 IFLSH 238
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
414-537 1.93e-08

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: 55.90  E-value: 1.93e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 414 SALACLVTIAAYLCSRVPLPCrrkPRDYtikVHMNLL-------LAVFLLD-TSFLLSEPVALTGSEAGCRASAIFLHFS 485
Cdd:cd15930   14 LSLTSLTTAMIILCLFRKLHC---TRNY---IHMNLFvsfilraIAVFIKDaVLFSSEDVDHCFVSTVGCKASMVFFQYC 87
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 530424522 486 LLTCLSWMGLEGYNLYRLVVEVFgTYVPGYLLKLSAMGWGFPIFLVTLVALV 537
Cdd:cd15930   88 VMANFFWLLVEGLYLHTLLVISF-FSERRYFWWYVLIGWGAPTVFVTVWIVA 138
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
403-589 2.53e-08

Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuronal migration and axon guidance in the CNS. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320659 [Multi-domain]  Cd Length: 254  Bit Score: 55.62  E-value: 2.53e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAylcsrvpLPCRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFL 482
Cdd:cd15993    4 LAIVTYSSVSASLAALVLTFSV-------LTCLRGLKSNTRGIHSNIAAALFLSELLFLLG--INRTENQFLCTVVAILL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 483 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVpGYLLKLSAMGWGFPIFLVTlvalvdvdnygpiiLAVHRTPEGVIYPSMC 562
Cdd:cd15993   75 HYFFLSTFAWLFVQGLHIYRMQTEARNVNF-GAMRFYYAIGWGVPAIITG--------------LAVGLDPEGYGNPDFC 139
                        170       180
                 ....*....|....*....|....*....
gi 530424522 563 WI--RDSLVSYITnlGLFSLVFLFNMAML 589
Cdd:cd15993  140 WIsiHDKLVWSFA--GPIVVVIVMNGVMF 166
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
404-658 5.97e-07

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: 51.65  E-value: 5.97e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 404 SLLSYVGCVVSALACLVTIAAYLCSRvPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSEPV---ALTGSEAG-CRASA 479
Cdd:cd15264    5 LIIYYLGFSISLVALAVALIIFLYFR-SLRCLRN------NIHCNLIVTFILRNVTWFIMQNTlteIHHQSNQWvCRLIV 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 480 IFLHFSLLTCLSWMGLEGYNLYRLVVEVFGT--YVPGYLLKLsamGWGFPIFLVTLVALVDVdnygpiilavhrtpegVI 557
Cdd:cd15264   78 TVYNYFQVTNFFWMFVEGLYLHTMIVWAYSAdkIRFWYYIVI---GWCIPCPFVLAWAIVKL----------------LY 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 558 YPSMCWI---RDSLVSYITnLGLFSLVFLFNMAMLATMV-VQILRLRPHTQKWSHVLTLLGLSLVLGLP-----WALIFF 628
Cdd:cd15264  139 ENEHCWLpksENSYYDYIY-QGPILLVLLINFIFLFNIVwVLITKLRASNTLETIQYRKAVKATLVLLPllgitYMLFFI 217
                        250       260       270
                 ....*....|....*....|....*....|.
gi 530424522 629 SFASG-TFQLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15264  218 NPGDDkTSRLVFIYFNTFLQSFQGLFVAVFY 248
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
414-537 4.75e-06

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: 48.81  E-value: 4.75e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 414 SALACLVTIAAYLCSRVPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSEPVALTGSEAG--------CRASAIFLHFS 485
Cdd:cd15987   14 TSLVSLTTAMVILCRFRKLHCTRN------FIHMNLFVSFILRAISVFIKDGVLYAEQDSDhcfvstveCKAVMVFFHYC 87
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 530424522 486 LLTCLSWMGLEGYNLYRLVVEvfgTYVPG--YLLKLSAMGWGFPIFLVTLVALV 537
Cdd:cd15987   88 VMSNYFWLFIEGLYLFTLLVE---TFFPErrYFYWYTIIGWGTPTICVTVWAVL 138
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
406-601 8.54e-06

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: 48.04  E-value: 8.54e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 406 LSYVGCVVSALACLVTIAAYLCSRvPLPCRRkprdytIKVHMNLLL------AVFLLDTSFLLSEPVALTGSEAGCRASA 479
Cdd:cd15260    7 VYIGGYSVSLIALIISLAIFFSFR-SLRCTR------ITIHMNLFIsfalnnLLWIVWYKLVVDNPEVLLENPIWCQALH 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 480 IFLHFSLLTCLSWMGLEGYNLYRLVVEVFgtyVPGY-LLKLS-AMGWGFPIFLVTLVALVDVdnygpiiLAVHRTpegvi 557
Cdd:cd15260   80 VLLQYFMVCNYFWMFCEGLYLHTVLVVAF---ISEKsLMRWFiAIGWGVPLVITAIYAGVRA-------SLPDDT----- 144
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 530424522 558 ypSMCWIRDSLVSYITNLG-----LFSLVFLFNMamlatMVVQILRLRP 601
Cdd:cd15260  145 --ERCWMEESSYQWILIVPvvlslLINLIFLINI-----VRVLLTKLRA 186
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
415-658 1.02e-05

vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of seven-transmembrane G protein-coupled receptors; Vasoactive intestinal peptide (VIP) receptor 1 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 pituitary adenylate cyclase activating polypeptide (PACAP). 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. VIP-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. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320397 [Multi-domain]  Cd Length: 268  Bit Score: 47.54  E-value: 1.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 415 ALACLVTIAAYLCSRVPLPCRRKprdytiKVHMNLLL-------AVFLLD-TSFLLSEPVALTGSEAGCRASAIFLHFSL 486
Cdd:cd15269   15 SLISLTAAMIILCLFRKLHCTRN------YIHMHLFMsfilraiAVFIKDaVLFESGEEDHCSVASVGCKAAMVFFQYCI 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 487 LTCLSWMGLEGYNLYRLVVEVFGT---YVPGYLLklsaMGWGFPIFLVTLVALVDV--DNYGpiilavhrTPEGVIYPSM 561
Cdd:cd15269   89 MANFFWLLVEGLYLHTLLAVSFFSerkYFWWYIL----IGWGAPSVFITAWSVARIyfEDVG--------CWDTIIESLL 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 562 CWIRDS--LVSYITNLGLFslvflfnmamlaTMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWAL-------IFFSFAS 632
Cdd:cd15269  157 WWIIKTpiLVSILVNFILF------------ICIIRILVQKLHSPDIGRNESSQYSRLAKSTLLLIplfgihyIMFAFFP 224
                        250       260
                 ....*....|....*....|....*..
gi 530424522 633 GTFQLVVLYLFSIIT-SFQGFLIFIWY 658
Cdd:cd15269  225 DNFKAEVKLVFELILgSFQGFVVAVLY 251
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
399-600 1.02e-05

insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of hormone receptors; member of the class B secretin-like seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Bombyx mori (silk worm) and its closely related proteins from arthropods. 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: 320390 [Multi-domain]  Cd Length: 270  Bit Score: 47.83  E-value: 1.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 399 HKHYLSLLSyvgcvVSALACLVTIAAYLCSRVPlpcrrkpRDYTIKVHMNLLLAVFLLDTSFLLSEPV----ALTGSEA- 473
Cdd:cd15262    5 YRFHVAALS-----VSVVTSLPAVFIFYSYKRL-------RITRVILHRNLLISIIIRNILVIISKVFvildALTSSGDd 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 474 --------GCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgyLLKLSAMGWGFPIFLVTLVAlvdvdnygpI 545
Cdd:cd15262   73 tvmnqnavVCRLLSIFERAARNAVFACMFVEGFYLHRLIVAVFAEKSS--IRFLYVIGAVLPLFPVIIWA---------I 141
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 530424522 546 ILAVHrtpegviYPSMCWIRD-SLVSYITNlgLFSLVFLF-NMAMLATMV-VQILRLR 600
Cdd:cd15262  142 IRALH-------NDHSCWVVDiEGVQWVLD--TPRLFILLvNTVLLVDIIrVLVTKLR 190
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
401-543 3.86e-05

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


Pssm-ID: 320399 [Multi-domain]  Cd Length: 267  Bit Score: 45.88  E-value: 3.86e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 401 HYLSLLSYVGCVVSALACLVTIAAYLCSRvPLPCrrkPRDYtikVHMNLL-------LAVFLLDTSFLLSEPV-ALTGSE 472
Cdd:cd15271    2 STVKLLYTVGYGTSLTSLITAVLIFCTFR-KLHC---TRNY---IHINLFvsfilraLAVFIKDAVLFADESVdHCTMST 74
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530424522 473 AGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFgTYVPGYLLKLSAMGWGFPIFLVTLVALV--DVDNYG 543
Cdd:cd15271   75 VACKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTF-TSDRKYFWWYILIGWGAPSVTVTVWVLTrlQYDNRG 146
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
406-542 1.25e-04

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


Pssm-ID: 320389 [Multi-domain]  Cd Length: 282  Bit Score: 44.28  E-value: 1.25e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 406 LSYVGCVVSALACLVTIAAYLCSRVpLPCRRKprdytiKVHMNLLLAVFL---------LDTSFLLSEPVA---LTGSEA 473
Cdd:cd15261    7 LEIVGLCLSLVSLIISLFIFSYFRT-LRNHRT------RIHKNLFLAILLqviirlvlyIDQAITRSRGSHtnaATTEGR 79
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530424522 474 G-------CRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLkLSAMGWGFPIFLVTLVALVDVDNY 542
Cdd:cd15261   80 TinstpilCEGFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVFSGKPNYLF-YYILGWGIPIVHTSAWAIVTLIKM 154
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
411-558 3.81e-04

G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR124 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, which also includes orphan GPR123 and GPR125. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Moreover, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. 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: 320664 [Multi-domain]  Cd Length: 268  Bit Score: 43.02  E-value: 3.81e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 411 CVVSALACL-VTIAAYLCSRVPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFSLLTC 489
Cdd:cd15998   11 CTALLLLCLfSTIITYILNHSSIHVSRK------GWHMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHYSSLST 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 490 LSWMGLEGYNLYRLVV---------EVfGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNY---GPIILAVHRTPEGVI 557
Cdd:cd15998   85 LLWMGVKARVLHKELTwrapppqegDP-ALPTPRPMLRFYLIAGGIPLIICGITAAVNIHNYrdhSPYCWLVWRPSLGAF 163

                 .
gi 530424522 558 Y 558
Cdd:cd15998  164 Y 164
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
412-662 4.50e-04

seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 42.80  E-value: 4.50e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 412 VVSALACLVTIAAYlcsrVPLPCRRKPRDYTIK----VHMNLLLAVFLLdtSFLLSEPVALTGSEAGCRASAIFLHFSLL 487
Cdd:cd14964   10 CLGLLGNLLVLLSL----VRLRKRPRSTRLLLAslaaCDLLASLVVLVL--FFLLGLTEASSRPQALCYLIYLLWYGANL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 488 TCLSWMGLEGYNLYRLVVEVFG---TYVPGYLLKLSAMGWGFPIFLVTLVALVdvdnygpiILAVHRTPEGV-IYPSMCW 563
Cdd:cd14964   84 ASIWTTLVLTYHRYFALCGPLKytrLSSPGKTRVIILGCWGVSLLLSIPPLVG--------KGAIPRYNTLTgSCYLICT 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 564 IRDSLVSYItnLGLFSLVFlfnMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL---------------PWALIFF 628
Cdd:cd14964  156 TIYLTWGFL--LVSFLLPL---VAFLVIFSRIVLRLRRRVRAIRSAASLNTDKNLKATksllilvitfllcwlPFSIVFI 230
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 530424522 629 SFASGT--FQLVVLYLFSI-ITSFQGFLIFIWYWSMR 662
Cdd:cd14964  231 LHALVAagQGLNLLSILANlLAVLASTLNPFIYCLGN 267
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
408-543 8.47e-04

G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR125 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, which also includes orphan receptors GPR123 and GPR124. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl. 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: 320665  Cd Length: 312  Bit Score: 42.16  E-value: 8.47e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 408 YVGCVVSALACLVTIAAYLCSRVPLPCRRKprdytiKVHM--NLLLAVFLldTSFLLSEPVALTGSEAGCRASAIFLHFS 485
Cdd:cd15999    9 YATAVVLLLCLLTIIVSYIYHHSLVRISRK------SWHMlvNLCFHIFL--TCAVFVGGINQTRNASVCQAVGIILHYS 80
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530424522 486 LLTCLSWMGLEGYNLYRLVVEVFGTYV--------PGYLLKLSAMGWGFPIFLVTLVALVDVDNYG 543
Cdd:cd15999   81 TLATVLWVGVTARNIYKQVTRKAKRCQdpdeppppPRPMLRFYLIGGGIPIIVCGITAAANIKNYG 146
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
402-666 8.88e-04

orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR113 is an orphan receptor that belongs to group VI adhesion-GPCRs along with GPR110, GPR111, GPR115, and GPR116. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. GPR113 contains a hormone binding domain and one EGF (epidermal grown factor) domain, and is primarily expressed in a subset of taste receptor cells. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320381 [Multi-domain]  Cd Length: 271  Bit Score: 41.67  E-value: 8.88e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 402 YLSLLSYVGCVVSALACLVTIAAYlCSRVPLPCRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIF 481
Cdd:cd15253    3 WLDFLSQVGLGASILALLLCLGIY-RLVWRSVVRNKISYFRHMTLVNIAFSLLLADTCFLGATFLSAGHESPLCLAAAFL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 482 LHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLS-AMGWGFPIflvtLVALVDVDNYGPiilavhrtPEGVIYPS 560
Cdd:cd15253   82 CHFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMvTLGYLCPL----LIAAATVAYYYP--------KRQYLHEG 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 561 MCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHT---QKWSHVLTLLGLSLVLGLP-----WALIFFSFAS 632
Cdd:cd15253  150 ACWLNGESGAIYAFSIPVLAIVLVNLLVLFVVLMKLMRPSVSEgppPEERKALLSIFKALLVLTPvfgltWGLGVATLTG 229
                        250       260       270
                 ....*....|....*....|....*....|....
gi 530424522 633 GTFQlVVLYLFSIITSFQGFLIFIWYWSMRLQAR 666
Cdd:cd15253  230 ESSQ-VSHYGFAILNAFQGVFILLFGCLMDKKVR 262
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
415-578 9.08e-04

vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Vasoactive intestinal peptide (VIP) receptor 2 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 pituitary adenylate cyclase activating polypeptide (PACAP). 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. VIP-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. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320652 [Multi-domain]  Cd Length: 269  Bit Score: 41.71  E-value: 9.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 415 ALACLVTIAAYLCSRVPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSEPVALTGSEA----------GCRASAIFLHF 484
Cdd:cd15986   15 SLIALTTGSTILCLFRKLHCTRN------YIHLNLFFSFILRAISVLVKDDILYSSSNTehctvppsliGCKVSLVILQY 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 485 SLLTCLSWMGLEGYNLYRLVVEVFGT--YVPGYLLklsaMGWGFPIFLVT--LVALVDVDNYGPIILAVHRTPEGVIYPS 560
Cdd:cd15986   89 CIMANFYWLLVEGLYLHTLLVVIFSEnrHFIVYLL----IGWGIPTVFIIawIVARIYLEDTGCWDTNDHSVPWWVIRIP 164
                        170
                 ....*....|....*...
gi 530424522 561 McwirdsLVSYITNLGLF 578
Cdd:cd15986  165 I------IISIILNFILF 176
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
409-533 1.48e-03

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


Pssm-ID: 320398 [Multi-domain]  Cd Length: 268  Bit Score: 40.94  E-value: 1.48e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 409 VGCVVSALACLVTIAAYLCSRvPLPCrrkPRDYtikVHMNLL-------LAVFLLDTSFLLSEPV-ALTGSEAGCRASAI 480
Cdd:cd15270   10 VGYSISIVSLCVAVAILVAFR-RLHC---PRNY---IHIQLFftfilkaIAVFIKDAALFQEDDTdHCSMSTVLCKVSVV 82
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530424522 481 FLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgYLLKLSAMGWGFPIFLVTL 533
Cdd:cd15270   83 FCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKR-YFWWLVLLGWGLPTLCTGT 134
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
439-658 1.55e-03

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


Pssm-ID: 320648 [Multi-domain]  Cd Length: 289  Bit Score: 41.07  E-value: 1.55e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 439 RDYTIKVHMNL--LLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgYL 516
Cdd:cd15982   57 KDKVVHTHIGVkeLDAVLMNDFQNAVDAPPVDKSQYVGCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTK-YL 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 517 LKLSAMGWGFPIFLVTLVALVDVdnygpiILAVHRTPEgVIYPSMCWIRDSLVsyITNLGLFSLVFLFNMAMLATMVVQI 596
Cdd:cd15982  136 WGFTLIGWGFPAVFVAAWAVVRA------TLADARCWE-LSAGDIKWIYQAPI--LAAIGLNFILFLNTVRVLATKIWET 206
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530424522 597 LRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQ----LVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15982  207 NAVGYDTRKQYRKLAKSTLVLVLVFGVHYIVFVCLPHTFTglgwEIRMHCELFFNSFQGFFVSIIY 272
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
402-536 1.82e-03

secretin receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Secretin receptor is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include vasoactive intestinal peptide (VIP), growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). 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 receptor, which is expressed in the brain, pancreas, stomach, kidney, and liver.


Pssm-ID: 320403 [Multi-domain]  Cd Length: 271  Bit Score: 40.88  E-value: 1.82e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 402 YLSLLSYVGCVVSaLACLVTIAAYLCSRVPLPCrrkPRDYtikVHMNLLLAvFLLDTSFLLSEPVALTGSE--------- 472
Cdd:cd15275    3 YLKTMYTVGYSVS-LVSLAIALAILCSFRRLHC---TRNY---IHMQLFLS-FILRAISIFIKDAVLFSSEddnhcdiyt 74
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530424522 473 AGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGT---YVPGYLlklsAMGWGFPIFLVTLVAL 536
Cdd:cd15275   75 VGCKVAMVFSNYCIMANYSWLLVEGLYLHSLLSISFFSerkHLWWYI----ALGWGSPLIFIISWAI 137
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
445-658 2.38e-03

glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon receptor (GCGR) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon-like peptide-1 receptor (GLP1R) and GLP2R. GCGR is activated by glucagon, which is 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. GCGR belongs 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: 320395 [Multi-domain]  Cd Length: 281  Bit Score: 40.57  E-value: 2.38e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 445 VHMNLLLAVFLLDTSFLLSEPVALT-----------------GSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRL-VVE 506
Cdd:cd15267   41 IHMNLFASFILKASSVLVIDGLLRTrysqkieddlsstwlsdEAVAGCRVAAVFMQYGIVANYCWLLVEGIYLHNLlVLA 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 507 VFG--TYVPGYLlklsAMGWGFP-IFLVTLVAlvdvdnygpiilaVHRTPEGViypsMCWirdslvSYITNLGLFSLV-F 582
Cdd:cd15267  121 VFPerSYFSLYL----CIGWGAPaLFVVPWVV-------------VKCLYENV----QCW------TSNDNMGFWWILrF 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 583 LFNMAMLATM-----VVQIL--RLRPHTQKWSHVLTLLGLSLVLGLP--------WALIFFSFASGTFQLVVLYLFSIIT 647
Cdd:cd15267  174 PVFLAILINFfifvrIIQILvsKLRARQMHYTDYKFRLAKSTLTLIPllgihevvFAFVTDEHAQGTLRSAKLFFDLFLS 253
                        250
                 ....*....|.
gi 530424522 648 SFQGFLIFIWY 658
Cdd:cd15267  254 SFQGLLVAVLY 264
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
403-658 4.98e-03

uncharacterized group of glucagon receptor-like proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This group consists of uncharacterized proteins with similarity to members of the glucagon receptor family of G protein-coupled receptors, which include glucagon receptor (GCGR), and glucagon-like peptide-1 receptor (GLP1R), and GLP2R. The glucagon 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: 320651 [Multi-domain]  Cd Length: 280  Bit Score: 39.53  E-value: 4.98e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSyvgcVVSALACLVTIAAYLCSRvplpcrrkprDYtikVHMNLLLAVFLLDTSFLLSEPV---------------- 466
Cdd:cd15985   14 LSLLT----LVSALLILTSIRKLHCTR----------NY---IHANLFASFILRAVSVIVKDTLlerrwgreimrvadwg 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 467 ALTGSEA--GCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLsAMGWGFPIFLVTlvalvdvdnygP 544
Cdd:cd15985   77 ELLSHKAaiGCRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYL-YLGWGTPVLFVV-----------P 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 545 IILAVHRTPEgviypSMCWIRDSLVSY--ITNLGLFsLVFLFNMAMLATMVVQIL-RLRPHTQKWSHVLTLLGLSLVLGL 621
Cdd:cd15985  145 WMLAKYLKEN-----KECWALNENMAYwwIIRIPIL-LASLINLLIFMRILKVILsKLRANQKGYADYKLRLAKATLTLI 218
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 530424522 622 PWALI---FFSFA-----SGTFQLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15985  219 PLFGIhevVFIFAtdeqtTGILRYIKVFFTLFLNSFQGFLVAVLY 263
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
409-564 4.99e-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: 39.55  E-value: 4.99e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 409 VGCVVSALACLVTIAAYLCSRvplpcrRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALtgSEAGCRASAIFLHFSLLT 488
Cdd:cd15988   10 IGCAVSCMALLILLAIYAAFW------RFIRSERSIILLNFCLSILASNILILVGQSQTL--SKGVCTMTAAFLHFFFLS 81
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530424522 489 CLSWMGLEGYNLYRLVVEVFGTYVpgYLLKLSAMGWGFPIFLVTL-VALVDVDNYGPiilavhrtpegviyPSMCWI 564
Cdd:cd15988   82 SFCWVLTEAWQSYLAVIGRMRTRL--VRKRFLCLGWGLPALVVAVsVGFTRTKGYGT--------------ASYCWL 142
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
403-658 5.60e-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: 39.34  E-value: 5.60e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 403 LSLLSYVGCVVSALACLVTIAAYLCSRvPLPCrrkPRDYtikVHMNLLlAVFLLDTSFLLSEPVAL-------------- 468
Cdd:cd15929    4 LQVMYTVGYSLSLAALVLALAILLGLR-KLHC---TRNY---IHANLF-ASFILRALSVLVKDALLprrysqkgdqdlws 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 469 ----TGSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGT---YVPGYLLklsaMGWGFPIFLVTLVALVD--V 539
Cdd:cd15929   76 tllsNQASLGCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSersIFRLYLL----LGWGAPVLFVVPWGIVKylY 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 540 DNYGpiilavhrtpegviypsmCWIRDSLVSY--ITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSL 617
Cdd:cd15929  152 ENTG------------------CWTRNDNMAYwwIIRLPILLAILINFFIFVRILKILVSKLRANQMCKTDYKFRLAKST 213
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 530424522 618 VLGLPWALI---FFSF-----ASGTFQLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15929  214 LTLIPLLGVhevVFAFvtdeqARGTLRFIKLFFELFLSSFQGLLVAVLY 262
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
405-658 7.27e-03

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


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 38.79  E-value: 7.27e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 405 LLSYVGCVVSALACLVTIAAYLCSRvPLPCRRKprdytiKVHMNLLLAVFLLDTSFLLSEPV---ALTGSEAGCRASAIF 481
Cdd:cd15446    6 IINYLGHCISVGALVVAFLLFLCLR-SIRCLRN------IIHWNLITTFILRNVMWFLLQMIdhnIHESNEVWCRCITTI 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 482 LHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLsAMGWGFPIflvtlvalvdvdnygPIILAvhrTPEGVIY--P 559
Cdd:cd15446   79 YNYFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFL-FIGWCIPC---------------PIIVA---WAIGKLYyeN 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 560 SMCWIRDS---LVSYITNlGLFSLVFLFNMAMLATMV-VQILRLRPHTQKWSHVLTLLGLSLVLGLP-----WALIFFSF 630
Cdd:cd15446  140 EQCWFGKEpgkYIDYIYQ-GPVILVLLINFVFLFNIVrILMTKLRASTTSETIQYRKAVKATLVLLPllgitYMLFFVNP 218
                        250       260
                 ....*....|....*....|....*....
gi 530424522 631 ASGTF-QLVVLYLFSIITSFQGFLIFIWY 658
Cdd:cd15446  219 GEDDIsQIVFIYFNSFLQSFQGFFVSVFY 247
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
402-656 8.18e-03

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: 38.83  E-value: 8.18e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 402 YLSLLSYVGCVVSALACLVTIAAYLCsrVPLPCRRKPRDYTIKVHM-NLLLAVFLLDTSFLLSEPVA-LTGSEAGCRASA 479
Cdd:cd15932    3 ALDYITYVGLGISILSLVLCLIIEAL--VWKSVTKNKTSYMRHVCLvNIALSLLIADIWFIIGAAIStPPNPSPACTAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 480 IFLHFSLLTCLSWMGLEGYNL-YRLVVeVFGTYVPGYLLKLS-AMGWGFPIFLVTlvalvdvdnygpIILAVHRTPEGVI 557
Cdd:cd15932   81 FFIHFFYLALFFWMLTLGLLLfYRLVL-VFHDMSKSTMMAIAfSLGYGCPLIIAI------------ITVAATAPQGGYT 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530424522 558 YPSMCWIrdslvSYITNLGLFSLVF------LFNMAMLATMVVQILRL----RPHTQKWShVLTLLGLSLVLGLPWALIF 627
Cdd:cd15932  148 RKGVCWL-----NWDKTKALLAFVIpalaivVVNFIILIVVIFKLLRPsvgeRPSKDEKN-ALVQIGKSVAILTPLLGLT 221
                        250       260       270
                 ....*....|....*....|....*....|...
gi 530424522 628 FSFASGTFQ----LVVLYLFSIITSFQGFLIFI 656
Cdd:cd15932  222 WGFGLGTMIdpksLAFHIIFAILNSFQGFFILV 254
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
475-543 9.86e-03

G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR123 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, and also includes orphan receptors GPR124 and GPR125. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells, yet its biological function remains to be determined. 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: 320666 [Multi-domain]  Cd Length: 275  Bit Score: 38.40  E-value: 9.86e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530424522 475 CRASAIFLHFSLLTCLSWMGLEGYNLYRLVVE----VFGTYVPGY----LLKLSAMGWGFPIFLVTLVALVDVDNYG 543
Cdd:cd16000   70 CQAVGIVLHYSTLSTMLWIGVTARNIYKQVTKkphlCQDTDQPPYpkqpLLRFYLVSGGVPFIICGITAATNINNYG 146
 
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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