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Conserved domains on  [gi|1635381377|ref|NP_001357368|]
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adhesion G-protein coupled receptor G1 isoform b precursor [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 ...
400-668 7.98e-159

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: 458.52  E-value: 7.98e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFS 479
Cdd:cd15995     1 KHYLTILTYVGCIISALASVFTIAFYLCSRRKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGGMFLHFS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 480 LLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAVHRTPEGVIYPSMCWIR 559
Cdd:cd15995    81 LLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHRSPEKVTYATICWIT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQLVVLYLFSI 639
Cdd:cd15995   161 DSLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTHKWSHVLTLLGLSLVLGIPWALAFFSFASGTFQLVIVYLFTI 240
                         250       260
                  ....*....|....*....|....*....
gi 1635381377 640 ITSFQGFLIFIWYWSMRLQARGGPSPLKS 668
Cdd:cd15995   241 INSLQGFLIFLWYWSMVLQARGGPSPLKS 269
PLL pfam18587
PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles ...
29-162 5.74e-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: 5.74e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377  29 REDFRFCSQRNQTHRSSLHYKPTPDLRISIENSEEALTVHAPFPAAHPASRSFPDPRGLYHFCLYWNRHAGRLHLLYGKR 108
Cdd:pfam18587   1 REDFRFCGQRNQTQNSSLIYEQTPELHISIENSEEALTIKAPFPPNPRASYSLPDPLGLYHFCLYWFRHAGTLHLRYGKQ 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1635381377 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 3.05e-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: 3.05e-27
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1635381377 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 2.21e-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: 70.41  E-value: 2.21e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1635381377 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 ...
400-668 7.98e-159

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: 458.52  E-value: 7.98e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFS 479
Cdd:cd15995     1 KHYLTILTYVGCIISALASVFTIAFYLCSRRKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGGMFLHFS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 480 LLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAVHRTPEGVIYPSMCWIR 559
Cdd:cd15995    81 LLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHRSPEKVTYATICWIT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQLVVLYLFSI 639
Cdd:cd15995   161 DSLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTHKWSHVLTLLGLSLVLGIPWALAFFSFASGTFQLVIVYLFTI 240
                         250       260
                  ....*....|....*....|....*....
gi 1635381377 640 ITSFQGFLIFIWYWSMRLQARGGPSPLKS 668
Cdd:cd15995   241 INSLQGFLIFLWYWSMVLQARGGPSPLKS 269
PLL pfam18587
PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles ...
29-162 5.74e-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: 5.74e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377  29 REDFRFCSQRNQTHRSSLHYKPTPDLRISIENSEEALTVHAPFPAAHPASRSFPDPRGLYHFCLYWNRHAGRLHLLYGKR 108
Cdd:pfam18587   1 REDFRFCGQRNQTQNSSLIYEQTPELHISIENSEEALTIKAPFPPNPRASYSLPDPLGLYHFCLYWFRHAGTLHLRYGKQ 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1635381377 109 DFLLSDKASSLLCFQHQEESLAQGPPLLATSVTSWWSPQNISLPSAASFTFSFH 162
Cdd:pfam18587  81 DFLLSDDASSLLCFRHQEESLSQGPPLLNVSYSSWWGPQNTSLPSASGYTFSFH 134
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
403-648 1.55e-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: 114.68  E-value: 1.55e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLL------SEPVALTGSEAGCRASAIFL 476
Cdd:pfam00002   4 LKVIYTVGYSLS-LVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVgdavlfNKQDLDHCSWVGCKVVAVFL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 477 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiilavhrtpegviYPSMC 556
Cdd:pfam00002  83 HYFFLANFFWMLVEGLYLYTLLVEVFFSERK-YFWWYLLIGWGVPALVVGIWAGVDPKGYG--------------EDDGC 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 557 WIRDSLVSYITNLGLFSLVFLFNMAMLaTMVVQIL--RLRPHTQKWSHVLTLLGLSLVLGL-------PWALIFFSFASG 627
Cdd:pfam00002 148 WLSNENGLWWIIRGPILLIILVNFIIF-INIVRILvqKLRETNMGKSDLKQYRRLAKSTLLllpllgiTWVFGLFAFNPE 226
                         250       260
                  ....*....|....*....|..
gi 1635381377 628 TFQLVV-LYLFSIITSFQGFLI 648
Cdd:pfam00002 227 NTLRVVfLYLFLILNSFQGFFV 248
GAIN_A pfam18619
GPCR-Autoproteolysis-INducing (GAIN) subdomain A; GPR56 is a a cell-surface G protein-coupled ...
173-220 3.05e-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: 3.05e-27
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1635381377 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 2.21e-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: 70.41  E-value: 2.21e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1635381377 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 8.34e-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: 8.34e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1635381377  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 ...
400-668 7.98e-159

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: 458.52  E-value: 7.98e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFS 479
Cdd:cd15995     1 KHYLTILTYVGCIISALASVFTIAFYLCSRRKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGGMFLHFS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 480 LLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAVHRTPEGVIYPSMCWIR 559
Cdd:cd15995    81 LLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHRSPEKVTYATICWIT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQLVVLYLFSI 639
Cdd:cd15995   161 DSLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTHKWSHVLTLLGLSLVLGIPWALAFFSFASGTFQLVIVYLFTI 240
                         250       260
                  ....*....|....*....|....*....
gi 1635381377 640 ITSFQGFLIFIWYWSMRLQARGGPSPLKS 668
Cdd:cd15995   241 INSLQGFLIFLWYWSMVLQARGGPSPLKS 269
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
400-665 9.84e-124

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: 368.67  E-value: 9.84e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFS 479
Cdd:cd15258     1 LHILTFISYVGCGISAIFLAITILTYIAFRKLRRDYPSKIHMNLCAALLLLNLAFLLSSWIASFGSDGLCIAVAVALHYF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 480 LLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAvhrTPEGVIYPSMCWIR 559
Cdd:cd15258    81 LLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPITIP---NGEGFQNDSFCWIR 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQ------KWSHVLTLLGLSLVLGLPWALIFFSFasGTFQLVV 633
Cdd:cd15258   158 DPVVFYITVVGYFGLTFLFNMVMLATVLVQICRLREKAQatprkrALHDLLTLLGLTFLLGLTWGLAFFAW--GPFNLPF 235
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1635381377 634 LYLFSIITSFQGFLIFIWYWSMRLQARGGPSP 665
Cdd:cd15258   236 LYLFAIFNSLQGFFIFIWYCSMKENVRKQWRA 267
PLL pfam18587
PTX/LNS-Like (PLL) domain; Adhesion G protein-coupled receptors (aGPCRs) play critical roles ...
29-162 5.74e-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: 5.74e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377  29 REDFRFCSQRNQTHRSSLHYKPTPDLRISIENSEEALTVHAPFPAAHPASRSFPDPRGLYHFCLYWNRHAGRLHLLYGKR 108
Cdd:pfam18587   1 REDFRFCGQRNQTQNSSLIYEQTPELHISIENSEEALTIKAPFPPNPRASYSLPDPLGLYHFCLYWFRHAGTLHLRYGKQ 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1635381377 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 ...
403-662 2.46e-67

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: 221.94  E-value: 2.46e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15443     4 LTYISIVGCSISAAASLLTILLHFFSRKQPKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQSTWLCRAAAALLHYSLLC 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAvhrTPEGVIYPSMCWIRDSL 562
Cdd:cd15443    84 CLTWMAIEGFHLYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFKREAYGPHTIP---TGTGYQNASMCWITSSK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 563 VSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGL-----SLVLGLPWALIFFSFasGTFQLVVLYLF 637
Cdd:cd15443   161 VHYVLVLGYAGLTSLFNLVVLAWVVRMLRRLRSRKQELGERARRDWVtvlglTCLLGTTWALAFFSF--GVFLIPQLFLF 238
                         250       260
                  ....*....|....*....|....*
gi 1635381377 638 SIITSFQGFLIFIWYWSMRLQARGG 662
Cdd:cd15443   239 TIINSLYGFFICLWYCTQRRRSDAS 263
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
400-660 4.57e-53

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: 183.16  E-value: 4.57e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 400 KHYLSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPValTGSEAGCRASAIFLHFS 479
Cdd:cd15040     1 EKALSIITYIGCGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLFGINS--TDNPVLCTAVAALLHYF 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 480 LLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviYPSMCWIR 559
Cdd:cd15040    79 LLASFMWMLVEALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGN-------------SSGYCWLS 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL------PWalIFFSFASGTFQLVV 633
Cdd:cd15040   146 NGNGLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQLRAAVSLffllglTW--IFGILAIFGARVVF 223
                         250       260
                  ....*....|....*....|....*..
gi 1635381377 634 LYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd15040   224 QYLFAIFNSLQGFFIFIFHCLRNKEVR 250
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
403-660 1.60e-49

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: 174.08  E-value: 1.60e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15997     4 LTLITYLGCGISSIFLGITLVTYLAFEKLRRDYPSKILINLCTALLMLNLVFLLNSWLSSFNNYGLCITVAAFLHYFLLA 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiILAVHRTPEGviYPSMCWIRDSL 562
Cdd:cd15997    84 SFTWMGLEAVHMYFALVKVFNIYIPNYILKFCIAGWGIPAVVVALVLAINKDFYG--NELSSDSLHP--STPFCWIQDDV 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 563 VSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQK--WSHVLTLLGLSLVLGL-----PWALIFFSFasGTFQLVVLY 635
Cdd:cd15997   160 VFYISVVAYFCLIFLCNISMFITVLIQIRSMKAKKPSrnWKQGFLHDLKSVASLTfllglTWGFAFFAW--GPVRIFFLY 237
                         250       260
                  ....*....|....*....|....*
gi 1635381377 636 LFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd15997   238 LFSICNTLQGFFIFVFHCLMKENVR 262
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
401-652 5.36e-47

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: 167.67  E-value: 5.36e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 401 HYLSLLSYVGCVVSALACLVTIAAYL---CSRRKPR-DYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFL 476
Cdd:cd15442     2 QTLVTISSAGCGVSMVFLIFTIILYFflrFTYQKFKsEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKALGGVT 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 477 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVAlvDVDNYG--PIILAVHRTpegviYPS 554
Cdd:cd15442    82 HYFLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLCLVGWGFPALVVTITG--SINSYGayTIMDMANRT-----TLH 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 555 MCWIRDS--LVSYITNLGLFSLVFLFNMAMLATMVVQILRLR------PHTQKWSHVLTLLGLSLVLGLPWALIFFSFas 626
Cdd:cd15442   155 LCWINSKhlTVHYITVCGYFGLTFLFNTVVLGLVAWKIFHLQsatagkEKCQAWKGGLTVLGLSCLLGVTWGLAFFTY-- 232
                         250       260
                  ....*....|....*....|....*.
gi 1635381377 627 GTFQLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15442   233 GSMSVPTVYIFALLNSLQGLFIFIWF 258
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
403-652 1.30e-46

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: 165.85  E-value: 1.30e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRKpRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd13952     4 LSIITYIGCSLSLVGLLLTIITYLLFPKL-RNLRGKILINLCLSLLLAQLLFLIGQLLTSSDRPVLCKALAILLHYFLLA 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIilavhrtpeGVIYPSMCWIRDSL 562
Cdd:cd13952    83 SFFWMLVEAFDLYRTFVKVFGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPS---------PGYGGEYCWLSNGN 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 563 VSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL-------PWALIFFSFASGtFQLVVLY 635
Cdd:cd13952   154 ALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSDRKQLRAYLKlfplmglTWIFGILAPFVG-GSLVFWY 232
                         250
                  ....*....|....*..
gi 1635381377 636 LFSIITSFQGFLIFIWY 652
Cdd:cd13952   233 LFDILNSLQGFFIFLIF 249
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
403-652 6.85e-44

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: 158.84  E-value: 6.85e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAG-CRASAIFLHFSLL 481
Cdd:cd15444     4 LTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKDIVGlCISVAVFLHYFLL 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 482 TCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiILAVHRTPEGVIyPSMCWIRDS 561
Cdd:cd15444    84 VSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYG--LGSYGKSPNGST-DDFCWINNN 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 562 LVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLG-------LPWALIFFSFasGTFQLVVL 634
Cdd:cd15444   161 IVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAgitfllgITWGFAFFAW--GPVNLAFM 238
                         250
                  ....*....|....*...
gi 1635381377 635 YLFSIITSFQGFLIFIWY 652
Cdd:cd15444   239 YLFAIFNTLQGFFIFIFY 256
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
403-656 7.08e-40

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: 147.73  E-value: 7.08e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15996     4 LTFITYIGCGISAIFSAATLLTYIAFEKLRRDYPSKILMNLSTALLFLNLVFLLDGWIASFEIDELCITVAVLLHFFLLA 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPIILAVHRTPEGViyPSMCWIRDSL 562
Cdd:cd15996    84 TFTWMGLEAIHMYIALVKVFNTYIRRYILKFCIIGWGLPALIVSIVLASTNDNYGYGYYGKDKDGQGG--DEFCWIKNPV 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 563 VSYITNLGLFSLVFLFNMAMLATMVVQIL---------RLRPHTQKwsHVLTLLGLSLVLGLPWALIFFSFasGTFQLVV 633
Cdd:cd15996   162 VFYVTCAAYFGIMFLMNVAMFIVVMVQICgrngkrsnrTLREEILR--NLRSVVSLTFLLGMTWGFAFFAW--GPVNLAF 237
                         250       260
                  ....*....|....*....|...
gi 1635381377 634 LYLFSIITSFQGFLIFIWYWSMR 656
Cdd:cd15996   238 MYLFTIFNSLQGLFIFVFHCALK 260
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
403-648 1.55e-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: 114.68  E-value: 1.55e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLL------SEPVALTGSEAGCRASAIFL 476
Cdd:pfam00002   4 LKVIYTVGYSLS-LVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVgdavlfNKQDLDHCSWVGCKVVAVFL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 477 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiilavhrtpegviYPSMC 556
Cdd:pfam00002  83 HYFFLANFFWMLVEGLYLYTLLVEVFFSERK-YFWWYLLIGWGVPALVVGIWAGVDPKGYG--------------EDDGC 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 557 WIRDSLVSYITNLGLFSLVFLFNMAMLaTMVVQIL--RLRPHTQKWSHVLTLLGLSLVLGL-------PWALIFFSFASG 627
Cdd:pfam00002 148 WLSNENGLWWIIRGPILLIILVNFIIF-INIVRILvqKLRETNMGKSDLKQYRRLAKSTLLllpllgiTWVFGLFAFNPE 226
                         250       260
                  ....*....|....*....|..
gi 1635381377 628 TFQLVV-LYLFSIITSFQGFLI 648
Cdd:pfam00002 227 NTLRVVfLYLFLILNSFQGFFV 248
GAIN_A pfam18619
GPCR-Autoproteolysis-INducing (GAIN) subdomain A; GPR56 is a a cell-surface G protein-coupled ...
173-220 3.05e-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: 3.05e-27
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1635381377 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 ...
403-652 1.19e-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: 109.34  E-value: 1.19e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLcSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEpvALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15933     4 LSIISYIGCGISIACLALTLIIFL-VLRVLSSDRFQIHKNLCVALLLAQILLLAGE--WAEGNKVACKVVAILLHFFFMA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGTyvpGYLLKL-SAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCW--IR 559
Cdd:cd15933    81 AFSWMLVEGLHLYLMIVKVFNY---KSKMRYyYFIGWGLPAIIVAISLAILFDDYGS--------------PNVCWlsLD 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DSLVSYITNLGLFslVFLFNMAMLA-----TMVVQILRLRPHTQKWShVLTLLGLSLVLGLP-----WALIFFSFASGTf 629
Cdd:cd15933   144 DGLIWAFVGPVIF--IITVNTVILIlvvkiTVSLSTNDAKKSQGTLA-QIKSTAKASVVLLPilgltWLFGVLVVNSQT- 219
                         250       260
                  ....*....|....*....|...
gi 1635381377 630 qLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15933   220 -IVFQYIFVILNSLQGLMIFLFH 241
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
403-650 7.55e-24

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: 101.57  E-value: 7.55e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIkVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15440     4 LTFITYIGCIISIVCLLLAFITFTCFRNLQCDRNT-IHKNLCLCLLIAEIVFLLG--IDQTENRTLCGVIAGLLHYFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVF---GTYVPGYLLklsaMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCWIR 559
Cdd:cd15440    81 AFSWMLLEGFQLYVMLVEVFepeKSRIKWYYL----FGYGLPALIVAVSAGVDPTGYGT--------------EDHCWLS 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLG----------LPWALIFFSFASGTf 629
Cdd:cd15440   143 TENGFIWSFVGPVIVVLLANLVFLGMAIYVMCRHSSRSASKKDASKLKNIRGWLKgsivlvvllgLTWTFGLLFINQES- 221
                         250       260
                  ....*....|....*....|.
gi 1635381377 630 qLVVLYLFSIITSFQGFLIFI 650
Cdd:cd15440   222 -IVMAYIFTILNSLQGLFIFI 241
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
403-656 6.02e-19

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: 86.90  E-value: 6.02e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd16007     4 LSVITWVGIVIS-LVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLIG--IDKTQYQIACPIFAGLLHFFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGT--------YVPGYLlklsamgwgFPIFLVTLVALVDVDNYGPiilavhrtpegviyPS 554
Cdd:cd16007    81 AFSWLCLEGVQLYLMLVEVFESeysrkkyyYLCGYC---------FPALVVGISAAIDYRSYGT--------------EK 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 555 MCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHTQK------WSHVLTLLGLSLVLGLPWALIFFSF 624
Cdd:cd16007   138 ACWLRVDNYFIWSFIGPVSFVIVVNLVFLMVTLHKMIRsssvLKPDSSRldniksWALGAITLLFLLGLTWAFGLLFINK 217
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1635381377 625 ASgtfqLVVLYLFSIITSFQGFLIFIWYWSMR 656
Cdd:cd16007   218 ES----VVMAYLFTTFNAFQGMFIFIFHCALQ 245
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
403-660 1.02e-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: 86.36  E-value: 1.02e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSR--RKPRDytiKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSL 480
Cdd:cd15438     4 LTLITKVGLSVSLFCLFLCILTFLFCRsiRGTRN---TIHLHLCLSLFLAHLIFLLG--INNTNNQVACAVVAGLLHYFF 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 481 LTCLSWMGLEGYNLYRLVVEVFGTYV--PGYLLklsAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCWI 558
Cdd:cd15438    79 LAAFCWMSLEGVELYLMVVQVFNTQSlkKRYLL---LIGYGVPLVIVAISAAVNSKGYGT--------------QRHCWL 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 559 ---RDSLVSYitnLGLFSLVFLFNMAMLATMVVQILR----LRPHTQKWSHVLTLLGLSLVLGL----PWALIFFSFASG 627
Cdd:cd15438   142 sleRGFLWSF---LGPVCLIILVNAIIFVITVWKLAEkfssINPDMEKLRKIRALTITAIAQLCilgcTWIFGFFQFSDS 218
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1635381377 628 TfqLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd15438   219 T--LVMSYLFTILNSLQGLFIFLLHCLLSKQVR 249
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
403-652 2.03e-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: 85.74  E-value: 2.03e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSR--RKPRdytIKVHMNLLLA-------------VFLLDTSFLLSEPVALTGSEA 467
Cdd:cd15041     4 VYYIYLVGYSLSLVALLPAIVIFLYFRslRCTR---IRLHINLFLSfilravfwiiwdlLVVYDRLTSSGVETVLMQNPV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 468 GCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFgTYVPGYLLKLSAMGWGFPIFLVTLVAlvdvdnygpIILAVHRTp 547
Cdd:cd15041    81 GCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAF-FSEPSSLKLYYAIGWGLPLVIVVIWA---------IVRALLSN- 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 548 egviypSMCWIRDSLVSY-----ITNLG--LFSLVFLFNmamlatmVVQIL--RLRPHTQKWSHVLTLLGLSLVLGLP-- 616
Cdd:cd15041   150 ------ESCWISYNNGHYewilyGPNLLalLVNLFFLIN-------ILRILltKLRSHPNAEPSNYRKAVKATLILIPlf 216
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1635381377 617 ---WALIFFSFASG-TFQLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15041   217 giqYLLTIYRPPDGsEGELVYEYFNAILNSSQGFFVAVIY 256
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
402-650 3.73e-18

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: 84.97  E-value: 3.73e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 402 YLSLLSYVGCVVSALACLVTIAAYLCSRrKPRDYTIKVHMNLLLAVFLLDTSFLLSePVALTGSEAGCRASAIFLHFSLL 481
Cdd:cd15039     3 ILGILTLIGLIISLVFLLLTLAVYALLP-ELRNLHGKCLMCLVLSLFVAYLLLLIG-QLLSSGDSTLCVALGILLHFFFL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 482 TCLSWMGLEGYNLYRlvveVFGTYVPGY--------LLKLSAMGWGFPIFLVTLVALVD-VDNYGPIILAVhrtpeGVIY 552
Cdd:cd15039    81 AAFFWLNVMSFDIWR----TFRGKRSSSsrskerkrFLRYSLYAWGVPLLLVAVTIIVDfSPNTDSLRPGY-----GEGS 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 553 psmCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL--------PWALIFFSF 624
Cdd:cd15039   152 ---CWISNPWALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKVQSRLRSDKQRFRLYLklfvimgvTWILEIISW 228
                         250       260
                  ....*....|....*....|....*.
gi 1635381377 625 ASGTFQlVVLYLFSIITSFQGFLIFI 650
Cdd:cd15039   229 FVGGSS-VLWYIFDILNGLQGVFIFL 253
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
403-660 2.04e-16

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: 79.58  E-value: 2.04e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIA--AYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSL 480
Cdd:cd15256     4 LSSITYVGCSLSIFCLAITLVtfAVLSSVSTIRNQRYHIHANLSFAVLVAQILLLIS--FRFEPGTLPCKIMAILLHFFF 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 481 LTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLkLSAMGWGFPIFLVTLVALVDVDNYGPIilavhrtpegviypSMCW--I 558
Cdd:cd15256    82 LSAFAWMLVEGLHLYSMVIKVFGSEESKHFY-YYGIGWGSPLLICIISLTSALDSYGES--------------DNCWlsL 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 559 RDSLVSYITNLGLFslVFLFNMAMLATMVVQILRLRPHTQKW---SHVLTLLGLSLVLGLPW---ALIFFSFASGTFQLV 632
Cdd:cd15256   147 ENGAIWAFVAPALF--VIVVNIGILIAVTRVISRISADNYKVhgdANAFKLTAKAVAVLLPIlgsSWVFGVLAVNTHALV 224
                         250       260
                  ....*....|....*....|....*...
gi 1635381377 633 VLYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd15256   225 FQYMFAIFNSLQGFFIFLFHCLLNSEVR 252
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
403-660 8.87e-16

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: 77.77  E-value: 8.87e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRrKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15439     4 LTVITYVGLIISLLCLFLAILTFLLCR-SIRNTSTSLHLQLSLCLFLADLLFLVG--IDRTDNKVLCSIIAGFLHYLFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLV-----VEVFGTYVPGYLLkLSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCW 557
Cdd:cd15439    81 CFAWMFLEAVHLFLTVrnlkvVNYFSSHRFKKRF-MYPVGYGLPAVIVAISAAVNPQGYGT--------------PKHCW 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 558 IRDSL-----------VSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTqkwSHVLTLLGLSLVLGLPWALIFFSFAS 626
Cdd:cd15439   146 LSMEKgfiwsflgpvcVIIVINLVLFCLTLWILREKLSSLNAEVSTLKNTR---LLTFKAIAQLFILGCTWILGLFQVGP 222
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1635381377 627 GTfqLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd15439   223 VA--TVMAYLFTITNSLQGVFIFLVHCLLNRQVR 254
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
345-388 2.21e-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: 70.41  E-value: 2.21e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1635381377 345 QCVFWveDPTLSSPGHWSSAGCETVR-RETQTSCFCNHLTYFAVL 388
Cdd:pfam01825   2 QCVFW--DFTNSTTGRWSTEGCTTVSlNDTHTVCSCNHLTSFAVL 44
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
403-652 2.27e-15

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: 76.52  E-value: 2.27e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15441     4 LKIVTYIGIGIS-LVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELLFLLG--INQTENLFPCKLIAILLHYFYLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEV-FGTYvpGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCWIrds 561
Cdd:cd15441    81 AFSWLLVESLHLYRMLTEPrDINH--GHMRFYYLLGYGIPAIIVGLSVGLRPDGYGN--------------PDFCWL--- 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 562 lvsYITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQLVVL------- 634
Cdd:cd15441   142 ---SVNETLIWSFAGPIAFVIVITLIIFILALRASCTLKRHVLEKASVRTDLRSSFLLLPLLGATWVFGLLAVnedsell 218
                         250
                  ....*....|....*....
gi 1635381377 635 -YLFSIITSFQGFLIFIWY 652
Cdd:cd15441   219 hYLFAGLNFLQGLFIFLFY 237
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
403-652 1.14e-14

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: 74.46  E-value: 1.14e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15252     4 LTRITQVGIIIS-LVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFLAELVFLIG--INTTTNKIFCSVIAGLLHYFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFgtYVPGYLLK-LSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCWIRDS 561
Cdd:cd15252    81 AFAWMFIEGIQLYLMLVEVF--ENEGSRHKnFYIFGYGSPAVIVGVSAALGYRYYGT--------------TKVCWLSTE 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 562 LVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRP------HTQKWSHVLTLLGLSLVLGLPWALIFFSFASgtfqL 631
Cdd:cd15252   145 NYFIWSFIGPATLIILLNLIFLGVAIYKMFRhtagLKPevscleNIRSWARGAIALLFLLGLTWIFGVLHINHAS----V 220
                         250       260
                  ....*....|....*....|.
gi 1635381377 632 VVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15252   221 VMAYLFTVSNSLQGMFIFLFH 241
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
403-660 2.38e-14

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: 73.41  E-value: 2.38e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd16006     4 LTVITWVGIVIS-LVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIG--IDKTEYKIACPIFAGLLHFFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGT--------YVPGYLlklsamgwgFPIFLVTLVALVDVDNYGPiilavhrtpegviyPS 554
Cdd:cd16006    81 AFAWMCLEGVQLYLMLVEVFESeysrkkyyYVAGYL---------FPATVVGVSAAIDYKSYGT--------------EK 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 555 MCWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHTQK------WSHVLTLLGLSLVLGLPWALIFFSF 624
Cdd:cd16006   138 ACWLRVDNYFIWSFIGPVTFIILLNLIFLVITLCKMVKhsntLKPDSSRleniksWVLGAFALLCLLGLTWSFGLLFINE 217
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1635381377 625 ASgtfqLVVLYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd16006   218 ET----IVMAYLFTIFNAFQGMFIFIFHCALQKKVR 249
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
402-650 2.62e-14

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: 73.32  E-value: 2.62e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 402 YLSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTIkVHMNLLLAVFLLDTSFLLSEpvALTGSEAGCRASAIFLHFSLL 481
Cdd:cd15931     3 FLEWINRVGVIVSLFCLGLAIFTFLLCRWIPKINTT-AHLHLCLCLSMSHTLFLAGI--EYVENELACTVMAGLLHYLFL 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 482 TCLSWMGLEGYNLYRLVVEVF-GTYVPGYLLK---LSAMGWGFPIFLVTLVALVDVDNYGpiilavhrtpegviYPSMCW 557
Cdd:cd15931    80 ASFVWMLLEALQLHLLVRRLTkVQVIQRDGLPrplLCLIGYGVPFLIVGVSALVYSDGYG--------------EAKMCW 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 558 IRDSLVSYITNLGLFSLVFLFNmAMLATMVVQILR-----LRPH--TQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQ 630
Cdd:cd15931   146 LSQERGFNWSFLGPVIAIIGIN-WILFCATLWCLRqtlsnMNSDisQLKDTRLLTFKAVAQLFILGCTWVLGLFQTNPVA 224
                         250       260
                  ....*....|....*....|
gi 1635381377 631 LVVLYLFSIITSFQGFLIFI 650
Cdd:cd15931   225 LVFQYLFTILNSLQGAFLFL 244
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
403-660 4.26e-14

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: 72.90  E-value: 4.26e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15436     4 LFVITWVGIVIS-LVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFIAELLFLIG--INRTQYTIACPIFAGLLHFFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVF-GTYVPGYLLKLSamGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCWIRDS 561
Cdd:cd15436    81 AFCWLCLEGVQLYLLLVEVFeSEYSRRKYFYLC--GYSFPALVVAVSAAIDYRSYGT--------------EKACWLRVD 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 562 LVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHTQK------WSHVLTLLGLSLVLGLPWALIFFSFASgtfqL 631
Cdd:cd15436   145 NYFIWSFIGPVTFVITLNLVFLVITLHKMVShsdlLKPDSSRldniksWALGAIALLFLLGLTWSFGLMFINEES----V 220
                         250       260
                  ....*....|....*....|....*....
gi 1635381377 632 VVLYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd15436   221 VMAYLFTIFNAFQGVFIFIFHCALQKKVR 249
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
403-652 2.74e-13

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: 71.06  E-value: 2.74e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSR--RKPRDYTIKVHMNLLLAVFLL---------------------DTSFLLSEP 459
Cdd:cd15257     4 LDIISTIGCVLSIAGLVITIIFHLHTRklRKSSVTWVLLNLCSSLLLFNIiftsgventnndyeistvpdrETNTVLLSE 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 460 VALTGSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLSAMGWGFPIFLV--TLVALVDVDNYG 537
Cdd:cd15257    84 EYVEPDTDVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQASAIGWGIPAVVVaiTLGATYRFPTSL 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 538 PIILAVHRTPEgviypsMCWIRDSLVSYITNLGLF-------SLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLS 610
Cdd:cd15257   164 PVFTRTYRQEE------FCWLAALDKNFDIKKPLLwgfllpvGLILITNVILFIMTSQKVLKKNNKKLTTKKRSYMKKIY 237
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1635381377 611 LVLGL------PWALIFFSFA-SGTFQLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15257   238 ITVSVavvfgiTWILGYLMLVnNDLSKLVFSYIFCITNTTQGVQIFILY 286
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
408-660 7.80e-13

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: 68.94  E-value: 7.80e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 408 YVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHM--NLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLTCLS 485
Cdd:cd15259     9 YAGAALCLLCLLATIITYIVFHRLIRISRKGRHMlvNLCLHLLLTCVVFVGG--INRTANQLVCQAVGILLHYSTLCTLL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 486 WMGLEGYNLYRLVVEV--------FGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGpiilavhrtpegviYPSMCW 557
Cdd:cd15259    87 WVGVTARNMYKQVTKTakppqdedQPPRPPKPMLRFYLIGWGIPLIICGITAAVNLDNYS--------------TYDYCW 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 558 IRDSlvsyiTNLGLF----SLVFLFNMAMLATMVVQIlrLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTF-QLV 632
Cdd:cd15259   153 LAWD-----PSLGAFygpaALIVLVNCIYFLRIYCQL--KGAPVSFQSQLRGAVITLFLYVAMWACGALAVSQRYFlDLV 225
                         250       260
                  ....*....|....*....|....*...
gi 1635381377 633 VLYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd15259   226 FSCLYGATCSSLGLFVLIHHCLSREDVR 253
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
403-660 5.30e-12

Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 66.51  E-value: 5.30e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd16005     4 LDVITWVGILLS-LVCLLICIFTFCFFRGLQSDRNTIHKNLCISLFVAELLFLIG--INRTDQPIACAVFAALLHFFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGTYvPGYLLKLSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCWIRDSL 562
Cdd:cd16005    81 AFTWMFLEGVQLYIMLVEVFESE-HSRRKYFYLVGYGMPALIVAVSAAVDYRSYGT--------------DKVCWLRLDT 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 563 VSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHT------QKWSHVLTLLGLSLVLGLPWALIFFSFASgtfqLV 632
Cdd:cd16005   146 YFIWSFIGPATLIIMLNVIFLGIALYKMFHhtaiLKPESgcldniKSWVIGAIALLCLLGLTWAFGLMYINEST----VI 221
                         250       260
                  ....*....|....*....|....*...
gi 1635381377 633 VLYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd16005   222 MAYLFTIFNSLQGMFIFIFHCVLQKKVR 249
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
342-389 8.34e-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: 8.34e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1635381377  342 VTLQCVFWVEdptlsSPGHWSSAGCETV-RRETQTSCFCNHLTYFAVLM 389
Cdd:smart00303   1 FNPICVFWDE-----SSGEWSTRGCELLeTNGTHTTCSCNHLTTFAVLM 44
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
403-652 8.82e-11

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: 62.94  E-value: 8.82e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAaYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15991     4 LKIITYTTVSLSLVALLITFI-LLVLIRTLRSNLHSIHKNLVAALFFSELIFLIG--INQTENPFVCTVVAILLHYFYMS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGTYVpGYLLKLSAMGWGFPIFLVTlvalvdvdnygpiiLAVHRTPEGVIYPSMCW--IRD 560
Cdd:cd15991    81 TFAWMFVEGLHIYRMLTEVRNINT-GHMRFYYVVGWGIPAIITG--------------LAVGLDPQGYGNPDFCWlsVQD 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 561 SLVSYITnlGLFSLVFLFNMAMLATMVVQILRLRPHTQK----WSHVLTLLGLSLVLGLPWALIFFSFASGTfqLVVLYL 636
Cdd:cd15991   146 TLIWSFA--GPIGIVVIINTVIFVLAAKASCGRRQRYFEksgvISMLRTAFLLLLLISATWLLGLMAVNSDT--LSFHYL 221
                         250
                  ....*....|....*.
gi 1635381377 637 FSIITSFQGFLIFIWY 652
Cdd:cd15991   222 FAIFSCLQGIFIFFFH 237
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
404-594 3.54e-10

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: 61.23  E-value: 3.54e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 404 SLLSYVGCVVS--ALACLVTIAAYLCSRRKPRDyTIkvHMNLLLAVFLLDTSFLLSEPVAL--TGSEAGCRASAIFLHFS 479
Cdd:cd15263     5 TTIYFIGYSLSlvALSLALWIFLYFKDLRCLRN-TI--HTNLMFTYILADLTWILTLTLQVsiGEDQKSCIILVVLLHYF 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 480 LLTCLSWMGLEGYNLYRLVVEVFGtyvpGYLLKLSA---MGWGFPIFLVTLVALvdVDNYGPIilAVHRTPEGVIYPSMC 556
Cdd:cd15263    82 HLTNFFWMFVEGLYLYMLVVETFS----GENIKLRVyafIGWGIPAVVIVIWAI--VKALAPT--APNTALDPNGLLKHC 153
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1635381377 557 -WIRDSLVSYITNlGLFSLVFLFNMAML-ATMVVQILRLR 594
Cdd:cd15263   154 pWMAEHIVDWIFQ-GPAILVLAVNLVFLvRIMWVLITKLR 192
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
403-651 3.21e-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: 58.35  E-value: 3.21e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15437     4 LTRITQLGIIIS-LICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELIFLIG--INMNANKLFCSIIAGLLHYFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFgtYVPGYLLK-LSAMGWGFPIFLVTLVALVDVDNYGPiilavhrtpegviyPSMCWIRDS 561
Cdd:cd15437    81 AFAWMCIEGIHLYLIVVGVI--YNKGFLHKnFYIFGYGSPAVVVGISAALGYKYYGT--------------TKVCWLSTE 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 562 LVSYITNLGLFSLVFLFNMAMLATMVVQILR----LRPHTQKWSHVLTLLGLSLvlglpwALIFFSFASGTF-------- 629
Cdd:cd15437   145 NNFIWSFIGPACLIILVNLLAFGVIIYKVFRhtamLKPEVSCYENIRSCARGAL------ALLFLLGATWIFgvlhvvyg 218
                         250       260
                  ....*....|....*....|..
gi 1635381377 630 QLVVLYLFSIITSFQGFLIFIW 651
Cdd:cd15437   219 SVVTAYLFTISNAFQGMFIFIF 240
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
414-531 4.26e-09

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: 57.83  E-value: 4.26e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 414 SALACLVTIAAYLCSRRK---PRDYtikVHMNLL-------LAVFLLD-TSFLLSEPVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15930    14 LSLTSLTTAMIILCLFRKlhcTRNY---IHMNLFvsfilraIAVFIKDaVLFSSEDVDHCFVSTVGCKASMVFFQYCVMA 90
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFgTYVPGYLLKLSAMGWGFPIFLVTLVALV 531
Cdd:cd15930    91 NFFWLLVEGLYLHTLLVISF-FSERRYFWWYVLIGWGAPTVFVTVWIVA 138
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
403-583 5.33e-09

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: 57.54  E-value: 5.33e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15993     4 LAIVTYSSVSAS-LAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLG--INRTENQFLCTVVAILLHYFFLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFGTYVpGYLLKLSAMGWGFPIFLVTlvalvdvdnygpiiLAVHRTPEGVIYPSMCWI--RD 560
Cdd:cd15993    81 TFAWLFVQGLHIYRMQTEARNVNF-GAMRFYYAIGWGVPAIITG--------------LAVGLDPEGYGNPDFCWIsiHD 145
                         170       180
                  ....*....|....*....|...
gi 1635381377 561 SLVSYITnlGLFSLVFLFNMAML 583
Cdd:cd15993   146 KLVWSFA--GPIVVVIVMNGVMF 166
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
403-536 7.53e-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: 57.17  E-value: 7.53e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRrKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVAltGSEAGCRASAIFLHFSLLT 482
Cdd:cd15255     4 LRTLSFIGCGVSLCALIVTFILFLAVG-VPKSERTTVHKNLIFALAAAEFLLMFSEWAK--GNQVACWAVTALLHLFFLA 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVfgTYVPGYLLKL-SAMGWGFPIFLVTLVALVDVDNY 536
Cdd:cd15255    81 AFSWMLVEGLLLWSKVVAV--NMSEDRRMKFyYVTGWGLPVVIVAVTLATSFNKY 133
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
403-652 3.20e-08

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: 55.21  E-value: 3.20e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRKPRDYTiKVHMNLLLAVFLLDTSFLLSepVALTGSEAGCRASAIFLHFSLLT 482
Cdd:cd15992     4 LKTLTWSSVGVTLGFLLLTFLFLLCLRALRSNKT-SIRKNGATALFLSELVFILG--INQADNPFACTVIAILLHFFYLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 483 CLSWMGLEGYNLYRLVVEVFG-TYVPGYLLKLsaMGWGFPIFLVTlvalvdvdnygpiiLAVHRTPEGVIYPSMCW--IR 559
Cdd:cd15992    81 TFSWLFLEGLHIYRMLSEVRDiNYGPMRFYYL--IGWGVPAFITG--------------LAVGLDPEGYGNPDFCWlsIY 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DSLVSYITNLGLFSL---VFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTfqLVVLYL 636
Cdd:cd15992   145 DTLIWSFAGPVAFAVsmnVFLYILSSRASCSAQQQSFEKKKGPVSGLRTAFTVLLLVSVTCLLALLSVNSDV--ILFHYL 222
                         250
                  ....*....|....*.
gi 1635381377 637 FSIITSFQGFLIFIWY 652
Cdd:cd15992   223 FAGFNCLQGPFIFLSH 238
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
399-594 6.53e-07

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: 51.29  E-value: 6.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 399 HKHYLSLLSyvgcvVSALACLVTIAAYLcSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPV----ALTGSEA------- 467
Cdd:cd15262     5 YRFHVAALS-----VSVVTSLPAVFIFY-SYKRLRITRVILHRNLLISIIIRNILVIISKVFvildALTSSGDdtvmnqn 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 468 --GCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgyLLKLSAMGWGFPIFLVTLVAlvdvdnygpIILAVHr 545
Cdd:cd15262    79 avVCRLLSIFERAARNAVFACMFVEGFYLHRLIVAVFAEKSS--IRFLYVIGAVLPLFPVIIWA---------IIRALH- 146
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1635381377 546 tpegviYPSMCWIRD-SLVSYITNlgLFSLVFLF-NMAMLATMV-VQILRLR 594
Cdd:cd15262   147 ------NDHSCWVVDiEGVQWVLD--TPRLFILLvNTVLLVDIIrVLVTKLR 190
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
404-652 1.60e-06

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


Pssm-ID: 320392 [Multi-domain]  Cd Length: 265  Bit Score: 50.11  E-value: 1.60e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 404 SLLSYVGCVVS--ALACLVTIAAYLCSRRKPRDytiKVHMNLLLAVFLLDTSFLLSEPV---ALTGSEAG-CRASAIFLH 477
Cdd:cd15264     5 LIIYYLGFSISlvALAVALIIFLYFRSLRCLRN---NIHCNLIVTFILRNVTWFIMQNTlteIHHQSNQWvCRLIVTVYN 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 478 FSLLTCLSWMGLEGYNLYRLVVEVFGT--YVPGYLLKLsamGWGFPIFLVTLVALVDVdnygpiilavhrtpegVIYPSM 555
Cdd:cd15264    82 YFQVTNFFWMFVEGLYLHTMIVWAYSAdkIRFWYYIVI---GWCIPCPFVLAWAIVKL----------------LYENEH 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 556 CWI---RDSLVSYITnLGLFSLVFLFNMAMLATMV-VQILRLRPHTQKWSHVLTLLGLSLVLGLP-----WALIFFSFAS 626
Cdd:cd15264   143 CWLpksENSYYDYIY-QGPILLVLLINFIFLFNIVwVLITKLRASNTLETIQYRKAVKATLVLLPllgitYMLFFINPGD 221
                         250       260
                  ....*....|....*....|....*..
gi 1635381377 627 G-TFQLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15264   222 DkTSRLVFIYFNTFLQSFQGLFVAVFY 248
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
414-531 2.28e-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: 49.58  E-value: 2.28e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 414 SALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAG--------CRASAIFLHFSLLTCLS 485
Cdd:cd15987    14 TSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQDSDhcfvstveCKAVMVFFHYCVMSNYF 93
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1635381377 486 WMGLEGYNLYRLVVEvfgTYVPG--YLLKLSAMGWGFPIFLVTLVALV 531
Cdd:cd15987    94 WLFIEGLYLFTLLVE---TFFPErrYFYWYTIIGWGTPTICVTVWAVL 138
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
415-652 2.93e-06

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: 49.47  E-value: 2.93e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 415 ALACLVTIAAYLCSRRK---PRDYtikVHMNLLL-------AVFLLD-TSFLLSEPVALTGSEAGCRASAIFLHFSLLTC 483
Cdd:cd15269    15 SLISLTAAMIILCLFRKlhcTRNY---IHMHLFMsfilraiAVFIKDaVLFESGEEDHCSVASVGCKAAMVFFQYCIMAN 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 484 LSWMGLEGYNLYRLVVEVFGT---YVPGYLLklsaMGWGFPIFLVTLVALVDV--DNYGpiilavhrTPEGVIYPSMCWI 558
Cdd:cd15269    92 FFWLLVEGLYLHTLLAVSFFSerkYFWWYIL----IGWGAPSVFITAWSVARIyfEDVG--------CWDTIIESLLWWI 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 559 RDS--LVSYITNLGLFslvflfnmamlaTMVVQILRLRPHTQKWSHVLTLLGLSLVLGLPWAL-------IFFSFASGTF 629
Cdd:cd15269   160 IKTpiLVSILVNFILF------------ICIIRILVQKLHSPDIGRNESSQYSRLAKSTLLLIplfgihyIMFAFFPDNF 227
                         250       260
                  ....*....|....*....|....
gi 1635381377 630 QLVVLYLFSIIT-SFQGFLIFIWY 652
Cdd:cd15269   228 KAEVKLVFELILgSFQGFVVAVLY 251
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
406-536 2.98e-06

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: 49.29  E-value: 2.98e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 406 LSYVGCVVSALACLVTIAAYlCSRRKPRDYTIKVHMNLLLAVFL---------LDTSFLLSEPVA---LTGSEAG----- 468
Cdd:cd15261     7 LEIVGLCLSLVSLIISLFIF-SYFRTLRNHRTRIHKNLFLAILLqviirlvlyIDQAITRSRGSHtnaATTEGRTinstp 85
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 469 --CRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLkLSAMGWGFPIFLVTLVALVDVDNY 536
Cdd:cd15261    86 ilCEGFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVFSGKPNYLF-YYILGWGIPIVHTSAWAIVTLIKM 154
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
415-537 6.89e-06

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: 48.19  E-value: 6.89e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 415 ALACLVTIAAYLCSRRK---PRDYtikVHMNLL-------LAVFLLDTSFLLSEPV-ALTGSEAGCRASAIFLHFSLLTC 483
Cdd:cd15271    15 SLTSLITAVLIFCTFRKlhcTRNY---IHINLFvsfilraLAVFIKDAVLFADESVdHCTMSTVACKAAVTFFQFCVLAN 91
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1635381377 484 LSWMGLEGYNLYRLVVEVFgTYVPGYLLKLSAMGWGFPIFLVTLVALV--DVDNYG 537
Cdd:cd15271    92 FFWLLVEGMYLQTLLLLTF-TSDRKYFWWYILIGWGAPSVTVTVWVLTrlQYDNRG 146
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
406-595 1.04e-05

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: 47.65  E-value: 1.04e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 406 LSYVGCVVSALACLVTIA--AYLCSRRKPRdytIKVHMNLLL------AVFLLDTSFLLSEPVALTGSEAGCRASAIFLH 477
Cdd:cd15260     7 VYIGGYSVSLIALIISLAifFSFRSLRCTR---ITIHMNLFIsfalnnLLWIVWYKLVVDNPEVLLENPIWCQALHVLLQ 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 478 FSLLTCLSWMGLEGYNLYRLVVEVFgtyVPGY-LLKLS-AMGWGFPIFLVTLVALVDVdnygpiiLAVHRTpegviypSM 555
Cdd:cd15260    84 YFMVCNYFWMFCEGLYLHTVLVVAF---ISEKsLMRWFiAIGWGVPLVITAIYAGVRA-------SLPDDT-------ER 146
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1635381377 556 CWIRDSLVSYITNLG-----LFSLVFLFNMamlatMVVQILRLRP 595
Cdd:cd15260   147 CWMEESSYQWILIVPvvlslLINLIFLINI-----VRVLLTKLRA 186
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
409-558 3.93e-05

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: 46.10  E-value: 3.93e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 409 VGCVVSALACLVTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALtgSEAGCRASAIFLHFSLLTCLSWMG 488
Cdd:cd15988    10 IGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVGQSQTL--SKGVCTMTAAFLHFFFLSSFCWVL 87
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1635381377 489 LEGYNLYRLVVEVFGTYVpgYLLKLSAMGWGFPIFLVTL-VALVDVDNYGPiilavhrtpegviyPSMCWI 558
Cdd:cd15988    88 TEAWQSYLAVIGRMRTRL--VRKRFLCLGWGLPALVVAVsVGFTRTKGYGT--------------ASYCWL 142
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
410-527 4.35e-05

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: 45.94  E-value: 4.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 410 GCVVSALACLVTIAAYLCSRRKPRDYtikVHMNLL-------LAVFLLDTSFLLSEPV-ALTGSEAGCRASAIFLHFSLL 481
Cdd:cd15270    13 SISIVSLCVAVAILVAFRRLHCPRNY---IHIQLFftfilkaIAVFIKDAALFQEDDTdHCSMSTVLCKVSVVFCHYCVM 89
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1635381377 482 TCLSWMGLEGYNLYRLVVEVFGTYVPgYLLKLSAMGWGFPIFLVTL 527
Cdd:cd15270    90 TNFFWLLVEAVYLNCLLASSFPRGKR-YFWWLVLLGWGLPTLCTGT 134
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
408-537 5.77e-05

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: 45.62  E-value: 5.77e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 408 YVGCVVSALACLVTIAAYLCSRRKPRDYTIKVHM--NLLLAVFLldTSFLLSEPVALTGSEAGCRASAIFLHFSLLTCLS 485
Cdd:cd15999     9 YATAVVLLLCLLTIIVSYIYHHSLVRISRKSWHMlvNLCFHIFL--TCAVFVGGINQTRNASVCQAVGIILHYSTLATVL 86
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 486 WMGLEGYNLYRLVVEVFGTYV--------PGYLLKLSAMGWGFPIFLVTLVALVDVDNYG 537
Cdd:cd15999    87 WVGVTARNIYKQVTRKAKRCQdpdeppppPRPMLRFYLIGGGIPIIVCGITAAANIKNYG 146
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
412-656 6.83e-05

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: 45.11  E-value: 6.83e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 412 VVSALACLVTIAAYLCSRRKPRdYTIKVHMNLLLAVFLLDTS-----FLLSEPVALTGSEAGCRASAIFLHFSLLTCLSW 486
Cdd:cd14964    10 CLGLLGNLLVLLSLVRLRKRPR-STRLLLASLAACDLLASLVvlvlfFLLGLTEASSRPQALCYLIYLLWYGANLASIWT 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 487 MGLEGYNLYRLVVEVFG---TYVPGYLLKLSAMGWGFPIFLVTLVALVdvdnygpiILAVHRTPEGV-IYPSMCWIRDSL 562
Cdd:cd14964    89 TLVLTYHRYFALCGPLKytrLSSPGKTRVIILGCWGVSLLLSIPPLVG--------KGAIPRYNTLTgSCYLICTTIYLT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 563 VSYItnLGLFSLVFlfnMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL---------------PWALIFFSFASG 627
Cdd:cd14964   161 WGFL--LVSFLLPL---VAFLVIFSRIVLRLRRRVRAIRSAASLNTDKNLKATksllilvitfllcwlPFSIVFILHALV 235
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1635381377 628 T--FQLVVLYLFSI-ITSFQGFLIFIWYWSMR 656
Cdd:cd14964   236 AagQGLNLLSILANlLAVLASTLNPFIYCLGN 267
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
415-572 2.39e-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: 43.64  E-value: 2.39e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 415 ALACLVTIAAYLCSRRK---PRDYtikVHMNLLLAVFLLDTSFLLSEPVALTGSEA----------GCRASAIFLHFSLL 481
Cdd:cd15986    15 SLIALTTGSTILCLFRKlhcTRNY---IHLNLFFSFILRAISVLVKDDILYSSSNTehctvppsliGCKVSLVILQYCIM 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 482 TCLSWMGLEGYNLYRLVVEVFGT--YVPGYLLklsaMGWGFPIFLVT--LVALVDVDNYGPIILAVHRTPEGVIYPSMcw 557
Cdd:cd15986    92 ANFYWLLVEGLYLHTLLVVIFSEnrHFIVYLL----IGWGIPTVFIIawIVARIYLEDTGCWDTNDHSVPWWVIRIPI-- 165
                         170
                  ....*....|....*
gi 1635381377 558 irdsLVSYITNLGLF 572
Cdd:cd15986   166 ----IISIILNFILF 176
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
411-566 3.18e-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: 3.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 411 CVVSALACL-VTIAAYLCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFSLLTCLSWMGL 489
Cdd:cd15998    11 CTALLLLCLfSTIITYILNHSSIHVSRKGWHMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHYSSLSTLLWMGV 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 490 EGYNLYRLVV---------EVfGTYVPGYLLKLSAMGWGFPIFLVTLVALVDVDNY---GPIILAVHRTPEGVIYPSMCW 557
Cdd:cd15998    91 KARVLHKELTwrapppqegDP-ALPTPRPMLRFYLIAGGIPLIICGITAAVNIHNYrdhSPYCWLVWRPSLGAFYIPVAL 169

                  ....*....
gi 1635381377 558 IRdsLVSYI 566
Cdd:cd15998   170 IL--LVTWI 176
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
409-652 4.10e-04

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: 42.89  E-value: 4.10e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 409 VGCVVSALACLVTIAAYLCSRRKprdytikVHMNLLLAVFLLDTSFLLSEPVALT-----------------GSEAGCRA 471
Cdd:cd15267    18 LGALLLALAILGGFSKLHCMRNA-------IHMNLFASFILKASSVLVIDGLLRTrysqkieddlsstwlsdEAVAGCRV 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 472 SAIFLHFSLLTCLSWMGLEGYNLYRL-VVEVFG--TYVPGYLlklsAMGWGFP-IFLVTLVAlvdvdnygpiilaVHRTP 547
Cdd:cd15267    91 AAVFMQYGIVANYCWLLVEGIYLHNLlVLAVFPerSYFSLYL----CIGWGAPaLFVVPWVV-------------VKCLY 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 548 EGViypsMCWirdslvSYITNLGLFSLV-FLFNMAMLATM-----VVQIL--RLRPHTQKWSHVLTLLGLSLVLGLP--- 616
Cdd:cd15267   154 ENV----QCW------TSNDNMGFWWILrFPVFLAILINFfifvrIIQILvsKLRARQMHYTDYKFRLAKSTLTLIPllg 223
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1635381377 617 -----WALIFFSFASGTFQLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15267   224 ihevvFAFVTDEHAQGTLRSAKLFFDLFLSSFQGLLVAVLY 264
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
402-530 4.64e-04

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: 42.42  E-value: 4.64e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 402 YLSLLSYVGCVVSaLACLVTIAAYLCSRRKPRDYTIKVHMNLLLAvFLLDTSFLLSEPVALTGSE---------AGCRAS 472
Cdd:cd15275     3 YLKTMYTVGYSVS-LVSLAIALAILCSFRRLHCTRNYIHMQLFLS-FILRAISIFIKDAVLFSSEddnhcdiytVGCKVA 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1635381377 473 AIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGT---YVPGYLlklsAMGWGFPIFLVTLVAL 530
Cdd:cd15275    81 MVFSNYCIMANYSWLLVEGLYLHSLLSISFFSerkHLWWYI----ALGWGSPLIFIISWAI 137
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
403-652 6.87e-04

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: 42.22  E-value: 6.87e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSyvgcVVSALACLVTIAAYLCSRRKprdytikVHMNLLLAVFLLDTSFLLSEPV----------------ALTGSE 466
Cdd:cd15985    14 LSLLT----LVSALLILTSIRKLHCTRNY-------IHANLFASFILRAVSVIVKDTLlerrwgreimrvadwgELLSHK 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 467 A--GCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLsAMGWGFPIFLVTlvalvdvdnygPIILAVH 544
Cdd:cd15985    83 AaiGCRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYL-YLGWGTPVLFVV-----------PWMLAKY 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 545 RTPEgviypSMCWIRDSLVSY--ITNLGLFsLVFLFNMAMLATMVVQIL-RLRPHTQKWSHVLTLLGLSLVLGLPWALI- 620
Cdd:cd15985   151 LKEN-----KECWALNENMAYwwIIRIPIL-LASLINLLIFMRILKVILsKLRANQKGYADYKLRLAKATLTLIPLFGIh 224
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1635381377 621 --FFSFA-----SGTFQLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15985   225 evVFIFAtdeqtTGILRYIKVFFTLFLNSFQGFLVAVLY 263
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
403-531 1.34e-03

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


Pssm-ID: 320650 [Multi-domain]  Cd Length: 290  Bit Score: 41.47  E-value: 1.34e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVS--ALACLVTIAAYLCSRRKPRDYtikVHMNLLLAVFLLDTSFLLSEPVALTGSE-------------- 466
Cdd:cd15984     4 LYLIYTVGYSISlgSLTVAVLILGYFRRLHCTRNY---IHMHLFLSFMLRAVSIFVKDAVLYSGSAleemeriteedlks 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1635381377 467 ------------AGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYvPGYLLKLSAMGWGFPIFLVTLVALV 531
Cdd:cd15984    81 iteappadkaqfVGCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTLFGWGLPAVFVTIWASV 156
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
403-652 1.67e-03

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


Pssm-ID: 341353 [Multi-domain]  Cd Length: 279  Bit Score: 40.88  E-value: 1.67e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRK--PRDYtikVHMNLLlAVFLLDTSFLLSEPVAL------------------ 462
Cdd:cd15929     4 LQVMYTVGYSLSLAALVLALAILLGLRKLhcTRNY---IHANLF-ASFILRALSVLVKDALLprrysqkgdqdlwstlls 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 463 TGSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGT---YVPGYLLklsaMGWGFPIFLVTLVALVD--VDNYG 537
Cdd:cd15929    80 NQASLGCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSersIFRLYLL----LGWGAPVLFVVPWGIVKylYENTG 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 538 piilavhrtpegviypsmCWIRDSLVSY--ITNLGLFSLVFLFNMAMLATMVVQILRLRPHTQKWSHVLTLLGLSLVLGL 615
Cdd:cd15929   156 ------------------CWTRNDNMAYwwIIRLPILLAILINFFIFVRILKILVSKLRANQMCKTDYKFRLAKSTLTLI 217
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1635381377 616 PWALI---FFSF-----ASGTFQLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15929   218 PLLGVhevVFAFvtdeqARGTLRFIKLFFELFLSSFQGLLVAVLY 262
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
433-652 1.74e-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: 1.74e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 433 RDYTIKVHMNL--LLAVFLLDTSFLLSEPVALTGSEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPgYL 510
Cdd:cd15982    57 KDKVVHTHIGVkeLDAVLMNDFQNAVDAPPVDKSQYVGCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTK-YL 135
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 511 LKLSAMGWGFPIFLVTLVALVDVdnygpiILAVHRTPEgVIYPSMCWIRDSLVsyITNLGLFSLVFLFNMAMLATMVVQI 590
Cdd:cd15982   136 WGFTLIGWGFPAVFVAAWAVVRA------TLADARCWE-LSAGDIKWIYQAPI--LAAIGLNFILFLNTVRVLATKIWET 206
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1635381377 591 LRLRPHTQKWSHVLTLLGLSLVLGLPWALIFFSFASGTFQ----LVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15982   207 NAVGYDTRKQYRKLAKSTLVLVLVFGVHYIVFVCLPHTFTglgwEIRMHCELFFNSFQGFFVSIIY 272
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
402-660 1.76e-03

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: 40.90  E-value: 1.76e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 402 YLSLLSYVGCVVSALACLVTIAAY-----LCSRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPVALTGSEAGCRASAIFL 476
Cdd:cd15253     3 WLDFLSQVGLGASILALLLCLGIYrlvwrSVVRNKISYFRHMTLVNIAFSLLLADTCFLGATFLSAGHESPLCLAAAFLC 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 477 HFSLLTCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLS-AMGWGFPIflvtLVALVDVDNYGPiilavhrtPEGVIYPSM 555
Cdd:cd15253    83 HFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMvTLGYLCPL----LIAAATVAYYYP--------KRQYLHEGA 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 556 CWIRDSLVSYITNLGLFSLVFLFNMAMLATMVVQILRLRPHT---QKWSHVLTLLGLSLVLGLP-----WALIFFSFASG 627
Cdd:cd15253   151 CWLNGESGAIYAFSIPVLAIVLVNLLVLFVVLMKLMRPSVSEgppPEERKALLSIFKALLVLTPvfgltWGLGVATLTGE 230
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1635381377 628 TFQlVVLYLFSIITSFQGFLIFIWYWSMRLQAR 660
Cdd:cd15253   231 SSQ-VSHYGFAILNAFQGVFILLFGCLMDKKVR 262
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
402-650 2.19e-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: 40.37  E-value: 2.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 402 YLSLLSYVGCVVSALA---CLVTIAAYLCSRRKPR-DYTIKVHM-NLLLAVFLLDTSFLLSEPVA-LTGSEAGCRASAIF 475
Cdd:cd15932     3 ALDYITYVGLGISILSlvlCLIIEALVWKSVTKNKtSYMRHVCLvNIALSLLIADIWFIIGAAIStPPNPSPACTAATFF 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 476 LHFSLLTCLSWMGLEGYNL-YRLVVeVFGTYVPGYLLKLS-AMGWGFPIFLVTlvalvdvdnygpIILAVHRTPEGVIYP 553
Cdd:cd15932    83 IHFFYLALFFWMLTLGLLLfYRLVL-VFHDMSKSTMMAIAfSLGYGCPLIIAI------------ITVAATAPQGGYTRK 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 554 SMCWIrdslvSYITNLGLFSLVF------LFNMAMLATMVVQILRL----RPHTQKWShVLTLLGLSLVLGLPWALIFFS 623
Cdd:cd15932   150 GVCWL-----NWDKTKALLAFVIpalaivVVNFIILIVVIFKLLRPsvgeRPSKDEKN-ALVQIGKSVAILTPLLGLTWG 223
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1635381377 624 FASGTFQ----LVVLYLFSIITSFQGFLIFI 650
Cdd:cd15932   224 FGLGTMIdpksLAFHIIFAILNSFQGFFILV 254
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
405-652 6.35e-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: 39.17  E-value: 6.35e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 405 LLSYVGCVVSALACLVTIAAYLCsRRKPRDYTIKVHMNLLLAVFLLDTSFLLSEPV---ALTGSEAGCRASAIFLHFSLL 481
Cdd:cd15446     6 IINYLGHCISVGALVVAFLLFLC-LRSIRCLRNIIHWNLITTFILRNVMWFLLQMIdhnIHESNEVWCRCITTIYNYFVV 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 482 TCLSWMGLEGYNLYRLVVEVFGTYVPGYLLKLsAMGWGFPIflvtlvalvdvdnygPIILAvhrTPEGVIY--PSMCWIR 559
Cdd:cd15446    85 TNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFL-FIGWCIPC---------------PIIVA---WAIGKLYyeNEQCWFG 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 560 DS---LVSYITNlGLFSLVFLFNMAMLATMV-VQILRLRPHTQKWSHVLTLLGLSLVLGLP-----WALIFFSFASGTF- 629
Cdd:cd15446   146 KEpgkYIDYIYQ-GPVILVLLINFVFLFNIVrILMTKLRASTTSETIQYRKAVKATLVLLPllgitYMLFFVNPGEDDIs 224
                         250       260
                  ....*....|....*....|...
gi 1635381377 630 QLVVLYLFSIITSFQGFLIFIWY 652
Cdd:cd15446   225 QIVFIYFNSFLQSFQGFFVSVFY 247
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
403-526 6.80e-03

glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon-like peptide-2 receptor (GLP2R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor (GCGR) and GLP1R. GLP2R is activated by glucagon-like peptide 2, which is derived from the large proglucagon precursor. 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 regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. GLP2R 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: 320394 [Multi-domain]  Cd Length: 280  Bit Score: 38.96  E-value: 6.80e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381377 403 LSLLSYVGCVVSALACLVTIAAYLCSRRK--PRDYtikVHMNLLLAVFLLDTSFLLSE----------PVALTG------ 464
Cdd:cd15266     4 LQLIYTIGYSLSLISLSLALLILLLLRKLhcTRNY---IHMNLFASFILRALAVLIKDivlystyskrPDDETGwisyls 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1635381377 465 --SEAGCRASAIFLHFSLLTCLSWMGLEGYNLYRLVVEVFGTYvPGYLLKLSAMGWGFPIFLVT 526
Cdd:cd15266    81 eeSSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSE-RRLLKKYMLIGWGTPVLFVV 143
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
469-537 9.33e-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: 9.33e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1635381377 469 CRASAIFLHFSLLTCLSWMGLEGYNLYRLVVE----VFGTYVPGY----LLKLSAMGWGFPIFLVTLVALVDVDNYG 537
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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