NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|251823835|ref|NP_036055|]
View 

CD97 antigen isoform 1 precursor [Mus musculus]

Protein Classification

EGF_CA and GPS domain-containing protein (domain architecture ID 12076838)

protein containing domains EGF_CA, GPS, and 7tm_GPCRs

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

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 ...
526-790 3.36e-115

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 cd15438:

Pssm-ID: 333717  Cd Length: 261  Bit Score: 354.07  E-value: 3.36e-115
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 526 DPRLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVglRCRLVAVMLHFCF 605
Cdd:cd15438    1 DWPLTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQV--ACAVVAGLLHYFF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 606 LAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFrKQGFLWSFSGPVA 685
Cdd:cd15438   79 LAAFCWMSLEGVELYLMVVQVFNTQSLKKRYLLLIGYGVPLVIVAIS-AAVNSKGYGTQRHCWLSL-ERGFLWSFLGPVC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 686 FIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLF 765
Cdd:cd15438  157 LIILVNAIIFVITVWKLAEKFSSINPDMEKLRKIRALTITAIAQLCILGCTWIFGFFQFSDSTLVMSYLFTILNSLQGLF 236
                        250       260
                 ....*....|....*....|....*
gi 251823835 766 LYVMLCLLNKKVREEYWKWACMVTG 790
Cdd:cd15438  237 IFLLHCLLSKQVREEYSRWLCAIAR 261
EGF_CA pfam07645
Calcium-binding EGF domain;
165-212 1.07e-11

Calcium-binding EGF domain;


:

Pssm-ID: 311536  Cd Length: 42  Bit Score: 62.37  E-value: 1.07e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 251823835  165 DVNECISGQNHCHQSTHCINKLGGYSCICRQGWKpvpgspNGPVSTVC 212
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYE------NNEDGTNC 42
EGF_CA pfam07645
Calcium-binding EGF domain;
214-248 2.89e-10

Calcium-binding EGF domain;


:

Pssm-ID: 311536  Cd Length: 42  Bit Score: 58.13  E-value: 2.89e-10
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 251823835  214 DVDECSSGQHQCHNSTVCKNTVGSYKCHCRPGWKP 248
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYEN 35
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
480-518 2.21e-09

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: 307782  Cd Length: 46  Bit Score: 55.84  E-value: 2.21e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 251823835  480 LICAFWK--AHNGNGYWDTDGCSMNGTG-----FCHCNHLTSFAIL 518
Cdd:pfam01825   1 PQCVFWDfdTGSGTGGWSTEGCELVTSSndthtVCSCNHLTSFAVL 46
EGF_CA pfam07645
Calcium-binding EGF domain;
69-118 3.73e-05

Calcium-binding EGF domain;


:

Pssm-ID: 311536  Cd Length: 42  Bit Score: 43.50  E-value: 3.73e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 251823835   69 DINECLLPGFSCGDFAMCKNSEGSYTCVCNLGYKllsgaesfVNESENTC 118
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYE--------NNEDGTNC 42
 
Name Accession Description Interval E-value
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
526-790 3.36e-115

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  Cd Length: 261  Bit Score: 354.07  E-value: 3.36e-115
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 526 DPRLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVglRCRLVAVMLHFCF 605
Cdd:cd15438    1 DWPLTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQV--ACAVVAGLLHYFF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 606 LAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFrKQGFLWSFSGPVA 685
Cdd:cd15438   79 LAAFCWMSLEGVELYLMVVQVFNTQSLKKRYLLLIGYGVPLVIVAIS-AAVNSKGYGTQRHCWLSL-ERGFLWSFLGPVC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 686 FIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLF 765
Cdd:cd15438  157 LIILVNAIIFVITVWKLAEKFSSINPDMEKLRKIRALTITAIAQLCILGCTWIFGFFQFSDSTLVMSYLFTILNSLQGLF 236
                        250       260
                 ....*....|....*....|....*
gi 251823835 766 LYVMLCLLNKKVREEYWKWACMVTG 790
Cdd:cd15438  237 IFLLHCLLSKQVREEYSRWLCAIAR 261
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
554-766 2.81e-70

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, characteristic 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: 306508  Cd Length: 244  Bit Score: 234.07  E-value: 2.81e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835  554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGLR-------CRLVAVMLHFCFLAAFCWMALEGVELYFLVVRV 626
Cdd:pfam00002  29 FRKLHCTRNYIHLNLFASFILRAILFLVGDAVLFNGEDLDhcswkvgCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEV 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835  627 FQGQGLSTWQRCLIGYGVPLLIVAISMAVvkmDGYGHATYCWLDFRkQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKF 706
Cdd:pfam00002 109 FFSERLYLWWYLLIGWGVPALVVGIWAGV---KGYGEDDGCWLSNE-NGLWWIIKGPVLLVILVNFIIFINIVRILVQKL 184
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 251823835  707 SEINPNMKKLRKaRVLTITSIAQLLVLGCTWgfGLFLFNPHST---WLSYIFTLLNCLQGLFL 766
Cdd:pfam00002 185 RETNMGESDLYQ-RRLAKSTLLLLPLLGITW--VLFAFNPDNVlrvVFLYLFLILNSFQGFFV 244
EGF_CA pfam07645
Calcium-binding EGF domain;
165-212 1.07e-11

Calcium-binding EGF domain;


Pssm-ID: 311536  Cd Length: 42  Bit Score: 62.37  E-value: 1.07e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 251823835  165 DVNECISGQNHCHQSTHCINKLGGYSCICRQGWKpvpgspNGPVSTVC 212
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYE------NNEDGTNC 42
EGF_CA pfam07645
Calcium-binding EGF domain;
214-248 2.89e-10

Calcium-binding EGF domain;


Pssm-ID: 311536  Cd Length: 42  Bit Score: 58.13  E-value: 2.89e-10
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 251823835  214 DVDECSSGQHQCHNSTVCKNTVGSYKCHCRPGWKP 248
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYEN 35
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
480-518 2.21e-09

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: 307782  Cd Length: 46  Bit Score: 55.84  E-value: 2.21e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 251823835  480 LICAFWK--AHNGNGYWDTDGCSMNGTG-----FCHCNHLTSFAIL 518
Cdd:pfam01825   1 PQCVFWDfdTGSGTGGWSTEGCELVTSSndthtVCSCNHLTSFAVL 46
EGF_CA smart00179
Calcium-binding EGF-like domain;
214-246 9.33e-09

Calcium-binding EGF-like domain;


Pssm-ID: 214542  Cd Length: 39  Bit Score: 53.79  E-value: 9.33e-09
                           10        20        30
                   ....*....|....*....|....*....|...
gi 251823835   214 DVDECSSGqHQCHNSTVCKNTVGSYKCHCRPGW 246
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGY 32
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
214-246 3.51e-08

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 52.25  E-value: 3.51e-08
                         10        20        30
                 ....*....|....*....|....*....|...
gi 251823835 214 DVDECSSGqHQCHNSTVCKNTVGSYKCHCRPGW 246
Cdd:cd00054    1 DIDECASG-NPCQNGGTCVNTVGSYRCSCPPGY 32
EGF_CA smart00179
Calcium-binding EGF-like domain;
165-197 8.71e-06

Calcium-binding EGF-like domain;


Pssm-ID: 214542  Cd Length: 39  Bit Score: 45.32  E-value: 8.71e-06
                           10        20        30
                   ....*....|....*....|....*....|...
gi 251823835   165 DVNECISGqNHCHQSTHCINKLGGYSCICRQGW 197
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGY 32
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
478-522 1.25e-05

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: 44.69  E-value: 1.25e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 251823835   478 HELICAFWKahNGNGYWDTDGCSM----NGTGFCHCNHLTSFAILMAQY 522
Cdd:smart00303   1 FNPICVFWD--ESSGEWSTRGCELletnGTHTTCSCNHLTTFAVLMDVP 47
EGF_CA pfam07645
Calcium-binding EGF domain;
69-118 3.73e-05

Calcium-binding EGF domain;


Pssm-ID: 311536  Cd Length: 42  Bit Score: 43.50  E-value: 3.73e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 251823835   69 DINECLLPGFSCGDFAMCKNSEGSYTCVCNLGYKllsgaesfVNESENTC 118
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYE--------NNEDGTNC 42
EGF_CA smart00179
Calcium-binding EGF-like domain;
69-101 4.61e-05

Calcium-binding EGF-like domain;


Pssm-ID: 214542  Cd Length: 39  Bit Score: 43.00  E-value: 4.61e-05
                           10        20        30
                   ....*....|....*....|....*....|...
gi 251823835    69 DINECLLPGfSCGDFAMCKNSEGSYTCVCNLGY 101
Cdd:smart00179   1 DIDECASGN-PCQNGGTCVNTVGSYRCECPPGY 32
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
69-103 8.34e-05

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 42.24  E-value: 8.34e-05
                         10        20        30
                 ....*....|....*....|....*....|....*
gi 251823835  69 DINECLLPGfSCGDFAMCKNSEGSYTCVCNLGYKL 103
Cdd:cd00054    1 DIDECASGN-PCQNGGTCVNTVGSYRCSCPPGYTG 34
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
165-197 8.83e-05

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 42.24  E-value: 8.83e-05
                         10        20        30
                 ....*....|....*....|....*....|...
gi 251823835 165 DVNECISGqNHCHQSTHCINKLGGYSCICRQGW 197
Cdd:cd00054    1 DIDECASG-NPCQNGGTCVNTVGSYRCSCPPGY 32
 
Name Accession Description Interval E-value
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
526-790 3.36e-115

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  Cd Length: 261  Bit Score: 354.07  E-value: 3.36e-115
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 526 DPRLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVglRCRLVAVMLHFCF 605
Cdd:cd15438    1 DWPLTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNNQV--ACAVVAGLLHYFF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 606 LAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFrKQGFLWSFSGPVA 685
Cdd:cd15438   79 LAAFCWMSLEGVELYLMVVQVFNTQSLKKRYLLLIGYGVPLVIVAIS-AAVNSKGYGTQRHCWLSL-ERGFLWSFLGPVC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 686 FIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLF 765
Cdd:cd15438  157 LIILVNAIIFVITVWKLAEKFSSINPDMEKLRKIRALTITAIAQLCILGCTWIFGFFQFSDSTLVMSYLFTILNSLQGLF 236
                        250       260
                 ....*....|....*....|....*
gi 251823835 766 LYVMLCLLNKKVREEYWKWACMVTG 790
Cdd:cd15438  237 IFLLHCLLSKQVREEYSRWLCAIAR 261
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
526-786 9.79e-98

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  Cd Length: 262  Bit Score: 308.29  E-value: 9.79e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 526 DPRLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEvgLRCRLVAVMLHFCF 605
Cdd:cd15931    1 DPFLEWINRVGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSMSHTLFLAGIEYVENE--LACTVMAGLLHYLF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 606 LAAFCWMALEGVELYFLVVRV-----FQGQGLSTWQRCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFrKQGFLWSF 680
Cdd:cd15931   79 LASFVWMLLEALQLHLLVRRLtkvqvIQRDGLPRPLLCLIGYGVPFLIVGVS-ALVYSDGYGEAKMCWLSQ-ERGFNWSF 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 681 SGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNC 760
Cdd:cd15931  157 LGPVIAIIGINWILFCATLWCLRQTLSNMNSDISQLKDTRLLTFKAVAQLFILGCTWVLGLFQTNPVALVFQYLFTILNS 236
                        250       260
                 ....*....|....*....|....*.
gi 251823835 761 LQGLFLYVMLCLLNKKVREEYWKWAC 786
Cdd:cd15931  237 LQGAFLFLVHCLLNKEVREEYIKWLT 262
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
526-786 7.06e-77

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  Cd Length: 263  Bit Score: 252.65  E-value: 7.06e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 526 DPRLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCF 605
Cdd:cd15439    1 DLALTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQLSLCLFLADLLFLVGIDRTDNKVL--CSIIAGFLHYLF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 606 LAAFCWMALEGVELYFLV-----VRVFQGQGLSTWQRCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFRKqGFLWSF 680
Cdd:cd15439   79 LACFAWMFLEAVHLFLTVrnlkvVNYFSSHRFKKRFMYPVGYGLPAVIVAIS-AAVNPQGYGTPKHCWLSMEK-GFIWSF 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 681 SGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNC 760
Cdd:cd15439  157 LGPVCVIIVINLVLFCLTLWILREKLSSLNAEVSTLKNTRLLTFKAIAQLFILGCTWILGLFQVGPVATVMAYLFTITNS 236
                        250       260
                 ....*....|....*....|....*.
gi 251823835 761 LQGLFLYVMLCLLNKKVREEYWKWAC 786
Cdd:cd15439  237 LQGVFIFLVHCLLNRQVREEYRRWIT 262
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
554-766 2.81e-70

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, characteristic 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: 306508  Cd Length: 244  Bit Score: 234.07  E-value: 2.81e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835  554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGLR-------CRLVAVMLHFCFLAAFCWMALEGVELYFLVVRV 626
Cdd:pfam00002  29 FRKLHCTRNYIHLNLFASFILRAILFLVGDAVLFNGEDLDhcswkvgCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEV 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835  627 FQGQGLSTWQRCLIGYGVPLLIVAISMAVvkmDGYGHATYCWLDFRkQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKF 706
Cdd:pfam00002 109 FFSERLYLWWYLLIGWGVPALVVGIWAGV---KGYGEDDGCWLSNE-NGLWWIIKGPVLLVILVNFIIFINIVRILVQKL 184
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 251823835  707 SEINPNMKKLRKaRVLTITSIAQLLVLGCTWgfGLFLFNPHST---WLSYIFTLLNCLQGLFL 766
Cdd:pfam00002 185 RETNMGESDLYQ-RRLAKSTLLLLPLLGITW--VLFAFNPDNVlrvVFLYLFLILNSFQGFFV 244
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
554-785 3.71e-69

invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors; This subgroup includes latrophilim-like proteins that are found in inveterbrates 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  Cd Length: 259  Bit Score: 231.38  E-value: 3.71e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLS 633
Cdd:cd15440   29 FRNLQCDRNTIHKNLCLCLLIAEIVFLLGIDQTENRTL--CGVIAGLLHYFFLAAFSWMLLEGFQLYVMLVEVFEPEKSR 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRCLIGYGVPLLIVAISMAvVKMDGYGHATYCWLDfRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTK--KFSEINP 711
Cdd:cd15440  107 IKWYYLFGYGLPALIVAVSAG-VDPTGYGTEDHCWLS-TENGFIWSFVGPVIVVLLANLVFLGMAIYVMCRhsSRSASKK 184
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 251823835 712 NMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEYWKWA 785
Cdd:cd15440  185 DASKLKNIRGWLKGSIVLVVLLGLTWTFGLLFINQESIVMAYIFTILNSLQGLFIFIFHCVLNEKVRKELRRWL 258
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
555-781 2.79e-65

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  Cd Length: 253  Bit Score: 220.52  E-value: 2.79e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQG-QGLS 633
Cdd:cd15040   31 KLRKRKPTKILLNLCLALLLANLLFLFGINSTDNPVL--CTAVAALLHYFLLASFMWMLVEALLLYLRLVKVFGTyPRHF 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRCLIGYGVPLLIVAISMAVVKMDGYGHATYCWLDFRkQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNM 713
Cdd:cd15040  109 ILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYCWLSNG-NGLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKK 187
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 251823835 714 KKLRKARVltITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEY 781
Cdd:cd15040  188 RKKTKAQL--RAAVSLFFLLGLTWIFGILAIFGARVVFQYLFAIFNSLQGFFIFIFHCLRNKEVRKAW 253
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
555-781 3.14e-64

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: 320090  Cd Length: 253  Bit Score: 217.44  E-value: 3.14e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVF-QGQGLS 633
Cdd:cd13952   31 KLRKRKRTKILLNLCLSLLLANLLFLVGISSTDNPVG--CTAVAALLHYFLLASFMWMLVEALLLYLRLVKVFgTYPRHF 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRCLIGYGVPLLIVAISMAVVKMDGYGHATYCWLDFRkQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNM 713
Cdd:cd13952  109 ILKYSLIGWGLPLIIVIITAAVDPDSYGGSSGYCWLSNG-NGLYYAFLGPVLLIILINLVIFVLILRKLLRLSAKRNKSE 187
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 251823835 714 KKLRKARVltITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEY 781
Cdd:cd13952  188 RKKTKRQL--RAALSLFFLLGLTWIFGILAILGARVVFQYLFAIFNSLQGFFIFIFYCLRNKEVRKAW 253
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
559-781 2.56e-53

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  Cd Length: 252  Bit Score: 186.76  E-value: 2.56e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 559 SSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVF-QGQGLSTWQr 637
Cdd:cd15933   34 SDRFQIHKNLCVALLLAQILLLAGEWAEGNKVA--CKVVAILLHFFFMAAFSWMLVEGLHLYLMIVKVFnYKSKMRYYY- 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 638 cLIGYGVPLLIVAISMAvVKMDGYGHATYCWLDFrKQGFLWSFSGPVAFIIFCNAAIFVItVWKLTKKFSEINPNMKKLR 717
Cdd:cd15933  111 -FIGWGLPAIIVAISLA-ILFDDYGSPNVCWLSL-DDGLIWAFVGPVIFIITVNTVILIL-VVKITVSLSTNDAKKSQGT 186
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 251823835 718 KARV-LTITSIAQLL-VLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEY 781
Cdd:cd15933  187 LAQIkSTAKASVVLLpILGLTWLFGVLVVNSQTIVFQYIFVILNSLQGLMIFLFHCVLNSEVRSAF 252
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
529-783 2.41e-52

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  Cd Length: 258  Bit Score: 184.35  E-value: 2.41e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 529 LELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEggEVGLRCRLVAVMLHFCFLAA 608
Cdd:cd16006    4 LTVITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIGIDKT--EYKIACPIFAGLLHFFFLAA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 609 FCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFRKQgFLWSFSGPVAFII 688
Cdd:cd16006   82 FAWMCLEGVQLYLMLVEVFESEYSRKKYYYVAGYLFPATVVGVS-AAIDYKSYGTEKACWLRVDNY-FIWSFIGPVTFII 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 689 FCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYV 768
Cdd:cd16006  160 LLNLIFLVITLCKMVKHSNTLKPDSSRLENIKSWVLGAFALLCLLGLTWSFGLLFINEETIVMAYLFTIFNAFQGMFIFI 239
                        250
                 ....*....|....*
gi 251823835 769 MLCLLNKKVREEYWK 783
Cdd:cd16006  240 FHCALQKKVRKEYSK 254
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
557-783 4.62e-52

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  Cd Length: 257  Bit Score: 183.48  E-value: 4.62e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVHLHLCICLFLGSIIFLVGVENEggEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQ 636
Cdd:cd15252   32 LQSDRTTIHKNLCISLFLAELVFLIGINTT--TNKIFCSVIAGLLHYFFLAAFAWMFIEGIQLYLMLVEVFENEGSRHKN 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 637 RCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFRKQgFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKL 716
Cdd:cd15252  110 FYIFGYGSPAVIVGVS-AALGYRYYGTTKVCWLSTENY-FIWSFIGPATLIILLNLIFLGVAIYKMFRHTAGLKPEVSCL 187
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 251823835 717 RKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15252  188 ENIRSWARGAIALLFLLGLTWIFGVLHINHASVVMAYLFTVSNSLQGMFIFLFHCVLSRKVRKEYYK 254
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
554-783 1.34e-51

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  Cd Length: 258  Bit Score: 182.04  E-value: 1.34e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLS 633
Cdd:cd16007   29 LRGLQTDRNTIHKNLCINLFLAELLFLIGIDKTQYQIA--CPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVEVFESEYSR 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFRKQgFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNM 713
Cdd:cd16007  107 KKYYYLCGYCFPALVVGIS-AAIDYRSYGTEKACWLRVDNY-FIWSFIGPVSFVIVVNLVFLMVTLHKMIRSSSVLKPDS 184
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 714 KKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd16007  185 SRLDNIKSWALGAITLLFLLGLTWAFGLLFINKESVVMAYLFTTFNAFQGMFIFIFHCALQKKVHKEYSK 254
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
557-783 5.50e-49

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  Cd Length: 258  Bit Score: 174.98  E-value: 5.50e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQ 636
Cdd:cd15436   32 LQTDRNTIHKNLCINLFIAELLFLIGINRTQYTIA--CPIFAGLLHFFFLAAFCWLCLEGVQLYLLLVEVFESEYSRRKY 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 637 RCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFRKQgFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKL 716
Cdd:cd15436  110 FYLCGYSFPALVVAVS-AAIDYRSYGTEKACWLRVDNY-FIWSFIGPVTFVITLNLVFLVITLHKMVSHSDLLKPDSSRL 187
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 251823835 717 RKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15436  188 DNIKSWALGAIALLFLLGLTWSFGLMFINEESVVMAYLFTIFNAFQGVFIFIFHCALQKKVRKEYSK 254
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
526-783 2.02e-46

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  Cd Length: 258  Bit Score: 167.81  E-value: 2.02e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 526 DPRLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCICLFLGSIIFLVGVENegGEVGLRCRLVAVMLHFCF 605
Cdd:cd16005    1 DLLLDVITWVGILLSLVCLLICIFTFCFFRGLQSDRNTIHKNLCISLFVAELLFLIGINR--TDQPIACAVFAALLHFFF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 606 LAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFRKQgFLWSFSGPVA 685
Cdd:cd16005   79 LAAFTWMFLEGVQLYIMLVEVFESEHSRRKYFYLVGYGMPALIVAVS-AAVDYRSYGTDKVCWLRLDTY-FIWSFIGPAT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 686 FIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLF 765
Cdd:cd16005  157 LIIMLNVIFLGIALYKMFHHTAILKPESGCLDNIKSWVIGAIALLCLLGLTWAFGLMYINESTVIMAYLFTIFNSLQGMF 236
                        250
                 ....*....|....*...
gi 251823835 766 LYVMLCLLNKKVREEYWK 783
Cdd:cd16005  237 IFIFHCVLQKKVRKEYGK 254
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
557-783 9.19e-45

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  Cd Length: 258  Bit Score: 163.12  E-value: 9.19e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEvgLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQ 636
Cdd:cd15437   32 IQSTRTTIHKNLCCSLFLAELIFLIGINMNANK--LFCSIIAGLLHYFFLAAFAWMCIEGIHLYLIVVGVIYNKGFLHKN 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 637 RCLIGYGVPLLIVAISmAVVKMDGYGHATYCWLDfRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKL 716
Cdd:cd15437  110 FYIFGYGSPAVVVGIS-AALGYKYYGTTKVCWLS-TENNFIWSFIGPACLIILVNLLAFGVIIYKVFRHTAMLKPEVSCY 187
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 251823835 717 RKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15437  188 ENIRSCARGALALLFLLGATWIFGVLHVVYGSVVTAYLFTISNAFQGMFIFIFLCVLSRKIQEEYYR 254
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
558-783 1.99e-44

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  Cd Length: 254  Bit Score: 162.04  E-value: 1.99e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 558 QSSRTMVHLHLCICLFLGSIIFLVGVENEggEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVR---VFQGQglst 634
Cdd:cd15441   33 QSNSNSIHKNLVACLLLAELLFLLGINQT--ENLFPCKLIAILLHYFYLSAFSWLLVESLHLYRMLTEprdINHGH---- 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 635 wQRC--LIGYGVPLLIVAISmAVVKMDGYGHATYCWLDFrKQGFLWSFSGPVAFIIFCNAAIFVITVWK-LTKKfseinp 711
Cdd:cd15441  107 -MRFyyLLGYGIPAIIVGLS-VGLRPDGYGNPDFCWLSV-NETLIWSFAGPIAFVIVITLIIFILALRAsCTLK------ 177
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 251823835 712 nMKKLRKARVLTI--TSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15441  178 -RHVLEKASVRTDlrSSFLLLPLLGATWVFGLLAVNEDSELLHYLFAGLNFLQGLFIFLFYCIFNKKVRRELKN 250
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
554-781 5.44e-40

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  Cd Length: 260  Bit Score: 149.69  E-value: 5.44e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEvgLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLS 633
Cdd:cd15256   32 VSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGT--LPCKIMAILLHFFFLSAFAWMLVEGLHLYSMVIKVFGSEESK 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRCLIGYGVPLLIVAISMAVVkMDGYGHATYCWLDFrKQGFLWSFSGPVAFIIFCNAAIfVITVWKLTKKFSEINPNM 713
Cdd:cd15256  110 HFYYYGIGWGSPLLICIISLTSA-LDSYGESDNCWLSL-ENGAIWAFVAPALFVIVVNIGI-LIAVTRVISRISADNYKV 186
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 251823835 714 KKLRKARVLTITSIAQLL-VLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEY 781
Cdd:cd15256  187 HGDANAFKLTAKAVAVLLpILGSSWVFGVLAVNTHALVFQYMFAIFNSLQGFFIFLFHCLLNSEVRAAF 255
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
566-786 2.39e-37

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: 320167  Cd Length: 270  Bit Score: 142.75  E-value: 2.39e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 566 LHLCICLFLGSIIFLVGVENEGGEVGLrCRLVAVMLHFCFLAAFCWMALEGVELYF-LVVRVFQGQGLSTWQR----CLI 640
Cdd:cd15039   41 MCLVLSLFVAYLLLLIGQLLSLGDSTL-CVALGILLHFFFLAAFFWLNVMSFDIWRtFRSKRSSSSRSKERKRflrySLY 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 641 GYGVPLLIVAISMAVVKMD-------GYGHaTYCWLDfRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNM 713
Cdd:cd15039  120 AWGVPLLLVAVTIIVDFSPptdslrpGYGE-GSCWIS-NPWALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKVQ 197
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 251823835 714 KKLRKARVLTITSIAQLLVLGCTWGFGL--FLFNpHSTWLSYIFTLLNCLQGLFLYVmLCLLNKKVREEYWKWAC 786
Cdd:cd15039  198 SRLRSDKQRFRLYLKLFVIMGVTWILEIisWFVG-GSSVLWYIFDILNGLQGVFIFL-IFVCKRRVLRLLKKKIR 270
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
562-780 1.38e-31

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 overexpressed 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  Cd Length: 267  Bit Score: 125.99  E-value: 1.38e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 562 TMVHLHLCICLFLGSIIFLVGVENEGGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFqgqglSTWQR---- 637
Cdd:cd15258   38 SKIHMNLCAALLLLNLAFLLSSWIASFGSDGLCIAVAVALHYFLLACLTWMGLEAFHLYLLLVKVF-----NTYIRryil 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 638 --CLIGYGVPLLIVAISMAvVKMDGYGHATYCWLDFRKQ-GFLWsFSGPVAFII-----FC-----NAAIFVITVWKLT- 703
Cdd:cd15258  113 klCLVGWGLPALLVTLVLS-VRSDNYGPITIPNGEGFQNdSFCW-IRDPVVFYItvvgyFGltflfNMVMLATVLVQICr 190
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 251823835 704 -KKFSEINPNMKKLRKarVLTITSIAqlLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREE 780
Cdd:cd15258  191 lREKAQATPRKRALHD--LLTLLGLT--FLLGLTWGLAFFAWGPFNLPFLYLFAIFNSLQGFFIFIWYCSMKENVRKQ 264
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
567-779 3.70e-31

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 overexpressed 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  Cd Length: 268  Bit Score: 124.73  E-value: 3.70e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 567 HLCI-----CLFLGSIIFLVGVENEGGEVGLR-CRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRC-- 638
Cdd:cd15932   43 HVCLvnialSLLIADIWFIIGAAISTPPNPSPaCTAATFFIHFFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIaf 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 639 LIGYGVPLLIVAISMAVVK-MDGYGHATYCWLDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKfSEINPNMKKLR 717
Cdd:cd15932  123 SLGYGCPLIIAIITVAATApQGGYTRKGVCWLNWDKTKALLAFVIPALAIVVVNFIILIVVIFKLLRP-SVGERPSKDEK 201
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 251823835 718 KARVLTITSIAQLL-VLGCTWGFGLF-LFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVRE 779
Cdd:cd15932  202 NALVQIGKSVAILTpLLGLTWGFGLGtMIDPKSLAFHIIFAILNSFQGFFILVFGTLLDSKVRE 265
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
566-783 7.94e-31

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: 123.62  E-value: 7.94e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 566 LHLCICLFLGSIIFLVGVE-NEGGEVGLrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLS-TWQRCLIGYG 643
Cdd:cd15997   42 INLCTALLMLNLVFLLNSWlSSFNNYGL-CITVAAFLHYFLLASFTWMGLEAVHMYFALVKVFNIYIPNyILKFCIAGWG 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 644 VPLLIVAISMAVVKmDGYGHATYCWLDFRKQGFLW---------SFSGPVAFIIFCNAAIFVITVWKLTKKFSeiNPNMK 714
Cdd:cd15997  121 IPAVVVALVLAINK-DFYGNELSSDSLHPSTPFCWiqddvvfyiSVVAYFCLIFLCNISMFITVLIQIRSMKA--KKPSR 197
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 715 KLRKARVLTITSIAQLLVL-GCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEyWK 783
Cdd:cd15997  198 NWKQGFLHDLKSVASLTFLlGLTWGFAFFAWGPVRIFFLYLFSICNTLQGFFIFVFHCLMKENVRKQ-WR 266
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
554-787 6.07e-29

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  Cd Length: 254  Bit Score: 118.02  E-value: 6.07e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEggEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLS 633
Cdd:cd15993   29 LRGLKSNTRGIHSNIAAALFLSELLFLLGINRT--ENQFLCTVVAILLHYFFLSTFAWLFVQGLHIYRMQTEARNVNFGA 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRCLIGYGVPLLIVAISMAVvKMDGYGHATYCWLDFRKQgFLWSFSGPVAFIIFCNAAIFVItVWKLTkkfseINPNM 713
Cdd:cd15993  107 MRFYYAIGWGVPAIITGLAVGL-DPEGYGNPDFCWISIHDK-LVWSFAGPIVVVIVMNGVMFLL-VARMS-----CSPGQ 178
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 251823835 714 KKLRKARVLTI--TSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEyWKWACM 787
Cdd:cd15993  179 KETKKTSVLMTlrSSFLLLLLISATWLFGLLAVNNSVLAFHYLHAILCCLQGLAVLLLFCVLNEEVQEA-WKLACL 253
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
554-779 8.47e-28

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  Cd Length: 254  Bit Score: 114.56  E-value: 8.47e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEggEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLS 633
Cdd:cd15991   29 IRTLRSNLHSIHKNLVAALFFSELIFLIGINQT--ENPFVCTVVAILLHYFYMSTFAWMFVEGLHIYRMLTEVRNINTGH 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRCLIGYGVPLLIVAISMAVvKMDGYGHATYCWLDFRKQgFLWSFSGPVAFIIFCNAAIFVITVWKLTKKfseinpNM 713
Cdd:cd15991  107 MRFYYVVGWGIPAIITGLAVGL-DPQGYGNPDFCWLSVQDT-LIWSFAGPIGIVVIINTVIFVLAAKASCGR------RQ 178
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 251823835 714 KKLRKARVLTITSIAQLLVL--GCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVRE 779
Cdd:cd15991  179 RYFEKSGVISMLRTAFLLLLliSATWLLGLMAVNSDTLSFHYLFAIFSCLQGIFIFFFHCIFNKEVRK 246
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
561-779 1.15e-26

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  Cd Length: 271  Bit Score: 111.78  E-value: 1.15e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 561 RTMVHLHLCICLFLGSIIFLVGVENEGGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQ--GQGLSTWQRC 638
Cdd:cd15253   42 RHMTLVNIAFSLLLADTCFLGATFLSAGHESPLCLAAAFLCHFFYLATFFWMLVQALMLFHQLLFVFHqlAKRSVLPLMV 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 639 LIGYGVPLLIVAISMAV-VKMDGYGHATYCWLDfRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTK-KFSEINPNMKkl 716
Cdd:cd15253  122 TLGYLCPLLIAAATVAYyYPKRQYLHEGACWLN-GESGAIYAFSIPVLAIVLVNLLVLFVVLMKLMRpSVSEGPPPEE-- 198
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 251823835 717 RKArvlTITSIAQLLVL----GCTWGFGLFLFNPHSTWLS-YIFTLLNCLQGLFLYVMLCLLNKKVRE 779
Cdd:cd15253  199 RKA---LLSIFKALLVLtpvfGLTWGLGVATLTGESSQVShYGFAILNAFQGVFILLFGCLMDKKVRE 263
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
566-783 1.45e-25

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 overexpressed 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  Cd Length: 271  Bit Score: 108.37  E-value: 1.45e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 566 LHLCICLFLGSIIFLVG--VENEGGEVGLrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFqgqglSTWQR------ 637
Cdd:cd15444   42 IQLCVALLLLNLVFLLDswIALYKDIVGL-CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVF-----NTYIRkyilkf 115
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 638 CLIGYGVPLLIVAISMAVVKmDGYGHATY-----------CWLDfRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKF 706
Cdd:cd15444  116 CIVGWGVPAVVVAIVLAVSK-DNYGLGSYgkspngstddfCWIN-NNIVFYITVVGYFCVIFLLNISMFIVVLVQLCRIK 193
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 251823835 707 SEINPNMKklRKARVLTITSIAQL-LVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEyWK 783
Cdd:cd15444  194 KQKQLGAQ--RKTSLQDLRSVAGItFLLGITWGFAFFAWGPVNLAFMYLFAIFNTLQGFFIFIFYCVAKENVRKQ-WR 268
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
559-783 3.78e-25

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  Cd Length: 303  Bit Score: 107.65  E-value: 3.78e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 559 SSRTMVHLHLCICLFLGSIIFLVGVEN-------------EGGEVGLR----------CRLVAVMLHFCFLAAFCWMALE 615
Cdd:cd15257   35 SSVTWVLLNLCSSLLLFNIIFTSGVENtnndyeistvpdrETNTVLLSeeyvepdtdvCTAVAALLHYFLLVTFMWNAVY 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 616 GVELYFLVVRVFQG-QGLSTWQRCLIGYGVPLLIVAISMAV---------VKMDGYGHATYCWLDFRKQGF------LWS 679
Cdd:cd15257  115 SAQLYLLLIRMMKPlPEMFILQASAIGWGIPAVVVAITLGAtyrfptslpVFTRTYRQEEFCWLAALDKNFdikkplLWG 194
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 680 FSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKK-LRKARVLTITSIaqlLVLGCTWGFG-LFLFNPHSTWL--SYIF 755
Cdd:cd15257  195 FLLPVGLILITNVILFIMTSQKVLKKNNKKLTTKKRsYMKKIYITVSVA---VVFGITWILGyLMLVNNDLSKLvfSYIF 271
                        250       260
                 ....*....|....*....|....*...
gi 251823835 756 TLLNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15257  272 CITNTTQGVQIFILYTWRTPEFRKLVSK 299
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
555-780 1.33e-24

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 (Alzhemer'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: 320169  Cd Length: 273  Bit Score: 105.38  E-value: 1.33e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSIIFLV--------GVENEGGEVGLR-----CRLVAVMLHFCFLAAFCWMALEGVELYF 621
Cdd:cd15041   30 RSLRCTRIRLHINLFISFILRAIFWILwdllvvydRLTSSGVETVLMqnpvgCKLLSVLKRYFKSANYFWMLVEGLYLHR 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 622 LVVRVFQGQGLSTWQRCLIGYGVPLLIVAIsMAVVKMdgYGHATYCWLDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWK 701
Cdd:cd15041  110 LIVVAFFSEPSSLKLYYAIGWGLPLVIVVA-WAIVRA--LLSDESCWIGYNNGHYEWILYGPNLLALLVNLFFLINILRI 186
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 702 L-TKKFSEINP---NMKKLRKARVLTITsiaqllVLGCTWGFGLFLFNPHSTWLS---YIFTLLNCLQGLFLYVMLCLLN 774
Cdd:cd15041  187 LlTKLRSHPNAepsNYRKAVKATLVLIP------LFGIQYLLTIYRPPDGSEGELvyeYFNAILNSSQGFFVAVIYCFLN 260

                 ....*.
gi 251823835 775 KKVREE 780
Cdd:cd15041  261 GEVQSE 266
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
564-773 1.58e-24

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  Cd Length: 277  Bit Score: 105.27  E-value: 1.58e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 564 VHLHLCICLFLGSIIFLVGVENEGGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQR-CLIGY 642
Cdd:cd15442   44 IHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKALGGVTHYFLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKlCLVGW 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 643 GVPLLIVAISMA--------VVKMDGYGHATYCWLDFRKQGFLW-SFSGPVAFIIFCNAAIFVITVWKLtkkFSEINPNM 713
Cdd:cd15442  124 GFPALVVTITGSinsygaytIMDMANRTTLHLCWINSKHLTVHYiTVCGYFGLTFLFNTVVLGLVAWKI---FHLQSATA 200
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 251823835 714 KKLR-KARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLL 773
Cdd:cd15442  201 GKEKcQAWKGGLTVLGLSCLLGVTWGLAFFTYGSMSVPTVYIFALLNSLQGLFIFIWFVIL 261
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
572-781 1.87e-24

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: 104.97  E-value: 1.87e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 572 LFLGSIIFLVGVENEGGEVGLrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFqgqglSTWQR------CLIGYGVP 645
Cdd:cd15996   49 LFLNLVFLLDGWIASFEIDEL-CITVAVLLHFFLLATFTWMGLEAIHMYIALVKVF-----NTYIRryilkfCIIGWGLP 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 646 LLIVAISMAVVK-----------MDGYGHATYCWLDfRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEinPNMK 714
Cdd:cd15996  123 ALIVSIVLASTNdnygygyygkdKDGQGGDEFCWIK-NPVVFYVTCAAYFGIMFLMNVAMFIVVMVQICGRNGK--RSNR 199
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 251823835 715 KLRKARVLTITSIAQL-LVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEY 781
Cdd:cd15996  200 TLREEILRNLRSVVSLtFLLGMTWGFAFFAWGPVNLAFMYLFTIFNSLQGLFIFVFHCALKENVQKQW 267
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
557-779 6.60e-24

brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediate direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320379  Cd Length: 253  Bit Score: 103.10  E-value: 6.60e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVglRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQ 636
Cdd:cd15251   33 IRSERSIILINFCLSIISSNILILVGQTQTLNKG--VCTMTAAFLHFFFLSSFCWVLTEAWQSYMAVTGRMRTRLIRKRF 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 637 RCLiGYGVPLLIVAISMAVVKMDGYGHATYCWLDFrKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKL 716
Cdd:cd15251  111 LCL-GWGLPALVVAVSVGFTRTKGYGTSSYCWLSL-EGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSRDGISDNAMASL 188
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 251823835 717 RKARVLtitsiaqLLVLGCTWGFG-LFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVRE 779
Cdd:cd15251  189 WSSCVV-------LPLLALTWMSAvLAMTDRRSVLFQILFAVFDSLQGFVIVMVHCILRREVQD 245
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
555-779 2.75e-22

brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediates direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320656  Cd Length: 267  Bit Score: 98.52  E-value: 2.75e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVglRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLST 634
Cdd:cd15990   34 RYIRSERSVILINFCLSIISSNALILIGQTQTRNKV--VCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRNRIIRK 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 635 WQRCLiGYGVPLLIVAISMAVVKMDGYGHATYCWLDFrKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMK 714
Cdd:cd15990  112 RFLCL-GWGLPALVVAISVGFTKAKGYGTVNYCWLSL-EGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKDGITDKKLK 189
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 251823835 715 KLRKARVLTITSIAQLLVLgcTWGFG-LFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVRE 779
Cdd:cd15990  190 ERAGASLWSSCVVLPLLAL--TWMSAvLAITDRRSALFQILFAVFDSLEGFVIVMVHCILRREVQD 253
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
557-779 7.57e-22

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  Cd Length: 291  Bit Score: 97.72  E-value: 7.57e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVHLHLCICLFLGSIIFLVGvENEGGEVGLrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQ 636
Cdd:cd15988   33 IRSERSIILLNFCLSILASNILILVG-QSQTLSKGV-CTMTAAFLHFFFLSSFCWVLTEAWQSYLAVIGRMRTRLVRKRF 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 637 RCLiGYGVPLLIVAISMAVVKMDGYGHATYCWLDFrKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKfSEINPNMKKL 716
Cdd:cd15988  111 LCL-GWGLPALVVAVSVGFTRTKGYGTASYCWLSL-EGGLLYAFVGPAAVIVLVNMLIGIIVFNKLMSR-DGISDKSKKQ 187
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 717 R-------KARVLTI-------------------------TSIAQLLVLGCTWGFG-LFLFNPHSTWLSYIFTLLNCLQG 763
Cdd:cd15988  188 RagseaepCSSLLLKcskcgvvssaamssatassamaslwSSCVVLPLLALTWMSAvLAMTDRRSILFQVLFAVFNSVQG 267
                        250
                 ....*....|....*.
gi 251823835 764 LFLYVMLCLLNKKVRE 779
Cdd:cd15988  268 FVIITVHCFLRREVQD 283
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
554-779 1.77e-21

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: 96.04  E-value: 1.77e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENegGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLS 633
Cdd:cd15992   29 LRALRSNKTSIRKNGATALFLSELVFILGINQ--ADNPFACTVIAILLHFFYLCTFSWLFLEGLHIYRMLSEVRDINYGP 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRCLIGYGVPLLIVAISMAvVKMDGYGHATYCWLDFRKQgFLWSFSGPVAFIIFCNAAIFVI----TVWKLTKKFSEI 709
Cdd:cd15992  107 MRFYYLIGWGVPAFITGLAVG-LDPEGYGNPDFCWLSIYDT-LIWSFAGPVAFAVSMNVFLYILssraSCSAQQQSFEKK 184
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 710 NPNMKKLRkarvltiTSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVRE 779
Cdd:cd15992  185 KGPVSGLR-------TAFTVLLLVSVTCLLALLSVNSDVILFHYLFAGFNCLQGPFIFLSHVVLLKEVRK 247
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
558-778 2.25e-21

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  Cd Length: 263  Bit Score: 95.69  E-value: 2.25e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 558 QSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQR 637
Cdd:cd15255   33 KSERTTVHKNLIFALAAAEFLLMFSEWAKGNQVA--CWAVTALLHLFFLAAFSWMLVEGLLLWSKVVAVNMSEDRRMKFY 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 638 CLIGYGVPLLIVAISMAVVkMDGYGHATYCWLDFRKQgFLWSFSGPVAFIIFCNAAIF----VITVWKLTKKFSEINPNM 713
Cdd:cd15255  111 YVTGWGLPVVIVAVTLATS-FNKYVADQHCWLNVQTD-IIWAFVGPVLFVLTVNTFVLfrvvMVTVSSARRRAKMLTPSS 188
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 251823835 714 KKLRKARVLTITSIAQLL----VLGCTWGFGLfLFNPHSTWlSYIFTLLNCLQGLFLYVMLCLLNKKVR 778
Cdd:cd15255  189 DLEKQIGIQIWATAKPVLvllpVLGLTWLCGV-LVHLSDVW-AYVFITLNSFQGLYIFLVYAIYNSEVR 255
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
555-779 2.70e-21

The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR116 (also known as Ig-Hepta) is an orphan receptor that belongs to group VI adhesion-GPCRs along with GPR110, GPR111, GPR113, and GPR115. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. GPR116 has 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. GPR116 is highly expressed in fetal and adult lung, and it has been shown to regulate lung surfactant levels as well as to stimulate breast cancer metastasis through a G(q)-p63-RhoGEF-Rho GTPase signaling pathway. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320382  Cd Length: 275  Bit Score: 95.64  E-value: 2.70e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCI-----CLFLGSIIFLV--GVENEGGEV-GLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRV 626
Cdd:cd15254   31 KSVTKNRTSYMRHVCIlniavSLLIADIWFIVvaAIQDQNYAVnGNVCVAATFFIHFFYLCVFFWMLALGLMLFYRLVFI 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 627 FQGQGLSTWQR---CLiGYGVPLLIVAISMAVVK-MDGYGHATYCWLDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKL 702
Cdd:cd15254  111 LHDTSKTIQKAvafCL-GYGCPLIISVITIAVTLpRDSYTRKKVCWLNWEDSKALLAFVIPALIIVAVNSIITVVVIVKI 189
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 251823835 703 TKKFSEINPNmKKLRKARVLTITSIAQLL-VLGCTWGFGLFLFNPHSTWLSYI-FTLLNCLQGLFLYVMLCLLNKKVRE 779
Cdd:cd15254  190 LRPSIGEKPS-KQERSSLFQIIKSIGVLTpLLGLTWGFGLATVIKGSSIVFHIlFTLLNAFQGLFILVFGTLWDKKVQE 267
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
555-780 1.82e-19

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  Cd Length: 268  Bit Score: 89.81  E-value: 1.82e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQgqglST 634
Cdd:cd15443   31 KQPKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQSTWLCRAAAALLHYSLLCCLTWMAIEGFHLYLLLVKVYN----IY 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 635 WQR-----CLIGYGVPLLIVaISMAVVKMDGYGH-----------ATYCWLDFRKQGFLWSFsGPVAFIIFCNAAIFVIT 698
Cdd:cd15443  107 IRRyvlklCVLGWGLPALIV-LLVLIFKREAYGPhtiptgtgyqnASMCWITSSKVHYVLVL-GYAGLTSLFNLVVLAWV 184
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 699 VWKLTKKFSEINpnmKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVR 778
Cdd:cd15443  185 VRMLRRLRSRKQ---ELGERARRDWVTVLGLTCLLGTTWALAFFSFGVFLIPQLFLFTIINSLYGFFICLWYCTQRRRSD 261

                 ..
gi 251823835 779 EE 780
Cdd:cd15443  262 AS 263
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
557-781 1.29e-17

brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediates direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320655  Cd Length: 293  Bit Score: 84.35  E-value: 1.29e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVglRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQ 636
Cdd:cd15989   35 IRSERSIILINFCLSIISSNILILVGQTQTHNKG--ICTMTTAFLHFFFLASFCWVLTEAWQSYMAVTGKIRTRLIRKRF 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 637 RCLiGYGVPLLIVAISMAVVKMDGYGHATYCWLDFrKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMK-- 714
Cdd:cd15989  113 LCL-GWGLPALVVAISMGFTKAKGYGTPHYCWLSL-EGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSRDGILDKKLKhr 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 715 -------------KLRKARVLTITSIAQ----------------LLVLGCTWGFG-LFLFNPHSTWLSYIFTLLNCLQGL 764
Cdd:cd15989  191 agqmsephsgltlKCAKCGVVSTTALSAttasnamaslwsscvvLPLLALTWMSAvLAMTDKRSILFQILFAVFDSLQGF 270
                        250
                 ....*....|....*..
gi 251823835 765 FLYVMLCLLNKKVREEY 781
Cdd:cd15989  271 VIVMVHCILRREVQDAF 287
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
564-768 8.73e-17

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: 81.80  E-value: 8.73e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 564 VHLHLCICLFLGSIIFLVG--VENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLS-TWQRCLI 640
Cdd:cd15995   40 VHMNLLLAIFLLDTSFLISepLALTGSEAA--CRAGGMFLHFSLLACLTWMGIEGYNLYRLVVEVFNTYVPHfLLKLCAV 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 641 GYGVPLLIVA------------ISMAVVK-MDGYGHATYCWLDFRKQGFLWSFsGPVAFIIFCNAAIFVITVWKLTKkfs 707
Cdd:cd15995  118 GWGLPIFLVTliflvdqdnygpIILAVHRsPEKVTYATICWITDSLISNITNL-GLFSLVFLFNMAMLATMVVEILR--- 193
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 251823835 708 eINPNMKKLRKARVLTITSiaqlLVLGCTWGFGLFLFNPHSTWLS--YIFTLLNCLQGLFLYV 768
Cdd:cd15995  194 -LRPRTHKWSHVLTLLGLS----LVLGIPWALAFFSFASGTFQLVivYLFTIINSLQGFLIFL 251
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
555-778 1.39e-16

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  Cd Length: 265  Bit Score: 80.92  E-value: 1.39e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSIIFLV-----GVENEGGEVGLrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQG 629
Cdd:cd15264   30 RSLRCLRNNIHCNLIVTFILRNVTWFImqntlTEIHHQSNQWV-CRLIVTVYNYFQVTNFFWMFVEGLYLHTMIVWAYSA 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 630 QGLSTWQRCLIGYGVPLLIVAIsMAVVKMdgYGHATYCWLDFRKQGFL-WSFSGPVAFIIFCN----AAIFVITVWKLTK 704
Cdd:cd15264  109 DKIRFWYYIVIGWCIPCPFVLA-WAIVKL--LYENEHCWLPKSENSYYdYIYQGPILLVLLINfiflFNIVWVLITKLRA 185
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 251823835 705 KFSEINPNMKKLRKARVLTitsiaqLLVLGCTwgFGLFLFNPHSTWLS-----YIFTLLNCLQGLFLYVMLCLLNKKVR 778
Cdd:cd15264  186 SNTLETIQYRKAVKATLVL------LPLLGIT--YMLFFINPGDDKTSrlvfiYFNTFLQSFQGLFVAVFYCFLNGEVR 256
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
567-779 7.67e-16

orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR111 and GPR115 are highly homologous orphan receptors that belong to group VI adhesion-GPCRs along with GPR110, GPR113, and GPR116. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS. Both GPR111 and GPR5 are present only in land-living animals and are predominantly expressed in the developing skin.


Pssm-ID: 320660  Cd Length: 267  Bit Score: 78.73  E-value: 7.67e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 567 HLCIC-----LFLGSIIFLVGVENEGGEVGLR-CRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCL- 639
Cdd:cd15994   43 HVCIVniatsLLIADVWFILASIVHNTALNYPlCVAATFFLHFFYLSLFFWMLTKALLILYGILLVFFKITKSVFIATAf 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 640 -IGYGVPLLIVAISMAVVK-MDGYGHATYCWLDFRKQGFLWSFSGPVAFIIFCNaaIFVITVWKLTKKFSEINPNMKKLR 717
Cdd:cd15994  123 sIGYGCPLVIAVLTVAITEpKKGYLRPEACWLNWDETKALLAFIIPALSIVVVN--LIVVGVVVVKTQRSSIGESCKQDV 200
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 251823835 718 KARVLTITSIAQLL-VLGCTWGFGL-FLFNPHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVRE 779
Cdd:cd15994  201 SNIIRISKNVAILTpLLGLTWGFGLaTIIDSRSLPFHIIFALLNAFQGFFILLFGTILDRKIRI 264
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
557-782 7.93e-15

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, brainstem 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  Cd Length: 260  Bit Score: 75.49  E-value: 7.93e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVH--LHLCICLFLGSIIFLVGVENEGGEvgLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQ-GQGLS 633
Cdd:cd15259   33 IRISRKGRHmlVNLCLHLLLTCVVFVGGINRTANQ--LVCQAVGILLHYSTLCTLLWVGVTARNMYKQVTKTAKpPQDED 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRC--------LIGYGVPLLIVAISMAvVKMDGYGHATYCWLDFRKqgFLWSFSGPVAFIIFCNAAIFVITVWKLTKK 705
Cdd:cd15259  111 QPPRPpkpmlrfyLIGWGIPLIICGITAA-VNLDNYSTYDYCWLAWDP--SLGAFYGPAALIVLVNCIYFLRIYCQLKGA 187
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 706 FSEINPNMKklrkarvltiTSIAQLLVLGCTWGFGLFLFN---PHSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREEYW 782
Cdd:cd15259  188 PVSFQSQLR----------GAVITLFLYVAMWACGALAVSqryFLDLVFSCLYGATCSSLGLFVLIHHCLSREDVRQSWR 257
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
561-777 1.22e-14

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  Cd Length: 267  Bit Score: 75.00  E-value: 1.22e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 561 RTMVHLHLCICLFLGSIIFLV--GVENEGGEV----GLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLST 634
Cdd:cd15260   36 RITIHMNLFISFALNNLLWIVwyKLVVDNPEVllenPIWCQALHVLLQYFMVCNYFWMFCEGLYLHTVLVVAFISEKSLM 115
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 635 WQRCLIGYGVPLLIVAIsMAVVKMDGYGHATYCWLDfrKQGFLWSFSGPVAFIIFCNaAIFVITVWK-LTKKFSEINPNM 713
Cdd:cd15260  116 RWFIAIGWGVPLVITAI-YAGVRASLPDDTERCWME--ESSYQWILIVPVVLSLLIN-LIFLINIVRvLLTKLRATSPNP 191
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 251823835 714 KK--LRKARVLTITSIAqLLVLgctwGFGLFLFNPH--STW---LSYIFTLLNCLQGLFLYVMLCLLNKKV 777
Cdd:cd15260  192 APagLRKAVRATLILIP-LLGL----QFLLIPFRPEpgAPLetiYQYVSALLTSLQGLCVAVLFCFCNGEV 257
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
561-778 1.83e-14

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  Cd Length: 272  Bit Score: 74.33  E-value: 1.83e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 561 RTMVHLHLCICLFLGSI--IFLVGVENEGGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRC 638
Cdd:cd15263   36 RNTIHTNLMFTYILADLtwILTLTLQVSIGEDQKSCIILVVLLHYFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYA 115
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 639 LIGYGVPLLIV---AISMAVVKM------DGYGHATYC-WldFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKL-TKKFS 707
Cdd:cd15263  116 FIGWGIPAVVIviwAIVKALAPTapntalDPNGLLKHCpW--MAEHIVDWIFQGPAILVLAVNLVFLVRIMWVLiTKLRS 193
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 251823835 708 EINPNMKKLRKArvltitSIAqLLVL----GCTwgFGLFLFNPHSTWLSYIFT----LLNCLQGLFLYVMLCLLNKKVR 778
Cdd:cd15263  194 ANTVETQQYRKA------AKA-LLVLipllGIT--YILVIAGPTEGIAANIFEyvraVLLSTQGFTVALFYCFLNTEVR 263
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
555-780 1.75e-13

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  Cd Length: 268  Bit Score: 71.42  E-value: 1.75e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSI--------IFLVGVENEGGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRV 626
Cdd:cd15269   30 RKLHCTRNYIHMHLFMSFILRAIavfikdavLFESGEEDHCSVASVGCKAAMVFFQYCIMANFFWLLVEGLYLHTLLAVS 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 627 FQGQGLSTWQRCLIGYGVP-LLIVAISMAVVKMDGYGhatyCWLDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKK 705
Cdd:cd15269  110 FFSERKYFWWYILIGWGAPsVFITAWSVARIYFEDVG----CWDTIIESLLWWIIKTPILVSILVNFILFICIIRILVQK 185
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 251823835 706 FSeiNPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPHS--TWLSYIFTL-LNCLQGLFLYVMLCLLNKKVREE 780
Cdd:cd15269  186 LH--SPDIGRNESSQYSRLAKSTLLLIPLFGIHYIMFAFFPDNfkAEVKLVFELiLGSFQGFVVAVLYCFLNGEVQAE 261
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
589-782 1.31e-12

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: 320595  Cd Length: 279  Bit Score: 69.02  E-value: 1.31e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 589 EVGLRCRLVAVMLHFCFLAAFCWMALEGVELY-FLVVRVFQGQGLstWQR-CLIGYGVPLLIVaISMAVVKMdgYGHATY 666
Cdd:cd15929   81 EASLGCRVAQVLMQYCVGANYYWLLVEGLYLHtLLVLAVLSERSL--FRLyLLLGWGAPVLFV-VPWGIVRY--LYENTG 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 667 CWLDFRKQGFLWSFSGPVAFIIFCNAAIFV----ITVWKL---TKKFSEInpnmkKLRKARVlTITSIAqllVLGCTWGF 739
Cdd:cd15929  156 CWTRNENMAIWWIIRGPILLAILINFFIFLrilkILVSKLranQMCFRDY-----KYRLAKS-TLTLIP---LLGVHEVV 226
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 251823835 740 GLFLFNPHST-WLSYI---FTL-LNCLQGLFLYVMLCLLNKKVREE---YW 782
Cdd:cd15929  227 FAFVTDEQARgTLRYIklfFELfLSSFQGFLVAVLYCFANKEVQSElrkKW 277
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
555-784 7.44e-12

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  Cd Length: 268  Bit Score: 66.53  E-value: 7.44e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSIIFLVG-----VENEGGEV---GLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRV 626
Cdd:cd15987   30 RKLHCTRNFIHMNLFVSFILRAISVFIKdgvlyAEQDSDHCfvsTVECKAVMVFFHYCVMSNYFWLFIEGLYLFTLLVET 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 627 FQGQGLSTWQRCLIGYGVPLLIVAIsMAVVKMdgYGHATYCWLDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKF 706
Cdd:cd15987  110 FFPERRYFYWYTIIGWGTPTICVTV-WAVLRL--HFDDTGCWDMNDNTALWWVIKGPVVGSIMINFVLFIGIIIILVQKL 186
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 707 SeiNPNMKKLRKARVLTITSIAQLLVLGCTWGFGLFLFNPH--STWLSYIFTL-LNCLQGLFLYVMLCLLNKKVREE-YW 782
Cdd:cd15987  187 Q--SPDIGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPEnvSKRERLVFELgLGSFQGFVVAVLYCFLNGEVQSEiKR 264

                 ..
gi 251823835 783 KW 784
Cdd:cd15987  265 KW 266
EGF_CA pfam07645
Calcium-binding EGF domain;
165-212 1.07e-11

Calcium-binding EGF domain;


Pssm-ID: 311536  Cd Length: 42  Bit Score: 62.37  E-value: 1.07e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 251823835  165 DVNECISGQNHCHQSTHCINKLGGYSCICRQGWKpvpgspNGPVSTVC 212
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYE------NNEDGTNC 42
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
554-778 1.07e-11

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


Pssm-ID: 320561  Cd Length: 265  Bit Score: 65.73  E-value: 1.07e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 554 VKPIQSSRTMVHLHLCICLFLGSIIFLVGVENEGGEVG----LRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQG 629
Cdd:cd15445   29 LRSIRCLRNIIHWNLITAFILRNATWFVVQLTMSPEVHqsnvVWCRLVTAAYNYFHVTNFFWMFGEGCYLHTAIVLTYST 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 630 QGLSTWQRCLIGYGVPLLIVaISMAVVKMdgYGHATYCWLDFRKQGFL-WSFSGPVAFIIFCNaAIFVITVWK--LTKKF 706
Cdd:cd15445  109 DKLRKWMFICIGWCIPFPII-VAWAIGKL--YYDNEKCWFGKRAGVYTdYIYQGPMILVLLIN-FIFLFNIVRilMTKLR 184
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 251823835 707 SEINPNMKKLRKARVLTITsiaQLLVLGCTwgFGLFLFNPHSTWLS-----YIFTLLNCLQGLFLYVMLCLLNKKVR 778
Cdd:cd15445  185 ASTTSETIQYRKAVKATLV---LLPLLGIT--YMLFFVNPGEDEISrivfiYFNSFLESFQGFFVSVFYCFLNSEVR 256
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
527-783 2.87e-11

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


Pssm-ID: 320400  Cd Length: 285  Bit Score: 64.72  E-value: 2.87e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 527 PRLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCI-CLFLGSIIFL--------VGVE-----NEGGEVGL 592
Cdd:cd15272    2 PSIRLMYNIGYGLSLVSLLIAVIIMLYFKKLHCPRNTIHINLFVsFILRAVLSFIkenllvqgVGFPgdvyyDSNGVIEF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 593 R-------CRLVAVMLHFCFLAAFCWMALEGVELYFLV-VRVFQgQGLSTWQRCLIGYGVPLLIVaISMAVVKmdGYGHA 664
Cdd:cd15272   82 KdegshweCKLFFTMFNYILGANYMWIFVEGLYLHMLIfVAVFS-ENSRVKWYILLGWLSPLLFV-LPWVFVR--ATLED 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 665 TYCWLDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTiTSIAQLLVLgctwgFG---- 740
Cdd:cd15272  158 TLCWNTNTNKGYFWIIRGPIVISIAINFLFFINIVRVLFTKLKASNTQESRPFRYRKLA-KSTLVLIPL-----FGvhym 231
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 251823835 741 LFLFNPHST--------WLsYIFTLLNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15272  232 VFVVLPDSMssdeaelvWL-YFEMFFNSFQGFIVALLFCFLNGEVQSEIKK 281
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
594-780 3.01e-11

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  Cd Length: 267  Bit Score: 64.37  E-value: 3.01e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 594 CRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAI-SMAVVKMDGYGhatyCWLDFr 672
Cdd:cd15271   77 CKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVwVLTRLQYDNRG----CWDDL- 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 673 KQGFLWSFSGPVAFIIFCNAAIFV----ITVWKLtkKFSEINPNMKKLRKaRVLTITsiaqlLVLGCTWG--FGLFLFNP 746
Cdd:cd15271  152 ESRIWWIIKTPILLSVFVNFLIFInvirILVQKL--KSPDVGGNDTSHYM-RLAKST-----LLLIPLFGvhYVVFAFFP 223
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 251823835 747 HSTWLS---YIFTLLNCLQGLFLYVMLCLLNKKVREE 780
Cdd:cd15271  224 EHVGVEarlYFELVLGSFQGFIVALLYCFLNGEVQAE 260
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
561-778 4.59e-11

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 (Alzhemer's and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression).


Pssm-ID: 320389  Cd Length: 282  Bit Score: 64.31  E-value: 4.59e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 561 RTMVHLHLCICLFLGSIIFLV-------GVENEGGEVGLR------------CRLVAVMLHFCFLAAFCWMALEGVELY- 620
Cdd:cd15261   36 RTRIHKNLFLAILLQVIIRLVlyidqaiTRSRGSHTNAATtegrtinstpilCEGFYVLLEYAKTVMFMWMFIEGLYLHn 115
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 621 FLVVRVFQGQGLSTWQrCLIGYGVPLLIVAISMAVVKMdgYGHATYCWLDFRKQGFLWSFSGPVAFIIFCN----AAIFV 696
Cdd:cd15261  116 IIVVSVFSGKPNYLFY-YILGWGIPIVHTSAWAIVTLI--KMKVNRCWFGYYLTPYYWILEGPRLAVILINlfflLNIIR 192
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 697 ITVWKLTKKFS-EINPNMKKLRKARVLtitsiaqLLVLGCTWGFGLFLFNPHST------WlSYIFTLLNCLQGLFLYVM 769
Cdd:cd15261  193 VLVSKLRESHSrEIEQVRKAVKAAIVL-------LPLLGITNILQMIPPPLTSVivgfavW-SYSTHFLTSFQGFFVALI 264

                 ....*....
gi 251823835 770 LCLLNKKVR 778
Cdd:cd15261  265 YCFLNGEVK 273
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
594-780 4.73e-11

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  Cd Length: 268  Bit Score: 63.99  E-value: 4.73e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 594 CRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAIsMAVVKMdgYGHATYCWLDFRK 673
Cdd:cd15930   77 CKASMVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTV-WIVARL--YFEDTGCWDINDE 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 674 QGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFS--EINPNMKK--LRKARvltitSIAQLLVLgctwgFG----LFLFN 745
Cdd:cd15930  154 SPYWWIIKGPILISILVNFVLFINIIRILLQKLRspDIGGNESSqyKRLAR-----STLLLIPL-----FGihyiVFAFF 223
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 251823835 746 PHST--WLSYIFTL-LNCLQGLFLYVMLCLLNKKVREE 780
Cdd:cd15930  224 PENIslGIRLYFELcLGSFQGFVVAVLYCFLNGEVQAE 261
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
593-780 5.14e-11

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  Cd Length: 271  Bit Score: 63.99  E-value: 5.14e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 593 RCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVaISMAVVKmdgYGHATY-CWLDF 671
Cdd:cd15275   76 GCKVAMVFSNYCIMANYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFI-ISWAIAR---YLHENEgCWDTR 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 672 RKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKF-------SEINpNMKKLRKARVLTITSiaqllvlgctwgFG---- 740
Cdd:cd15275  152 RNAWIWWIIRGPVILSIFVNFILFLNILRILMRKLrapdmrgNEFS-QYKRLAKSTLLLIPL------------FGlhyi 218
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 251823835 741 LFLFNPHST-------WLSYIFTlLNCLQGLFLYVMLCLLNKKVREE 780
Cdd:cd15275  219 LFAFFPEDVssgtmeiWLFFELA-LGSFQGFVVAVLYCFLNGEVQLE 264
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
594-786 1.86e-10

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  Cd Length: 281  Bit Score: 62.53  E-value: 1.86e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 594 CRLVAVMLHFCFLAAFCWMALEGVELY-FLVVRVFQGQGLSTWQRClIGYGVPLLIVaISMAVVKMDGYGHAtyCWLDFR 672
Cdd:cd15267   88 CRAATVFMQYGIVANYCWLLVEGIYLHnLLVLAVFSERSYFSLYLC-IGWGAPMLFL-VPWVVVKYLYENIQ--CWSSND 163
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 673 KQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEinPNMK----KLRKARVlTITSIAqllVLGCTWGFGLFLFNPHS 748
Cdd:cd15267  164 NMGFWWILRFPVFLAILINFFIFVRIIQILVSKLRA--HQMRytdyKFRLAKS-TLTLIP---LLGIHEVVFAFVTDEHA 237
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 251823835 749 T----WLSYIFTL-LNCLQGLFLYVMLCLLNKKVREEYWK-WAC 786
Cdd:cd15267  238 QgtlrLVKLFFDLfLSSFQGLLVAVLYCFVNKEVQSELRKrWHR 281
EGF_CA pfam07645
Calcium-binding EGF domain;
214-248 2.89e-10

Calcium-binding EGF domain;


Pssm-ID: 311536  Cd Length: 42  Bit Score: 58.13  E-value: 2.89e-10
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 251823835  214 DVDECSSGQHQCHNSTVCKNTVGSYKCHCRPGWKP 248
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYEN 35
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
554-778 5.81e-10

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  Cd Length: 264  Bit Score: 60.74  E-value: 5.81e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 554 VKPIQSSRTMVHLHLCICLFLGSII-FLVGVEN----EGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQ 628
Cdd:cd15446   29 LRSIRCLRNIIHWNLITTFILRNVMwFLLQMIDhnihESNEVW--CRCITTIYNYFVVTNFFWMFVEGCYLHTAIVMTYS 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 629 GQGLSTWQRCLIGYGVPLLIVaISMAVVKMdgYGHATYCWLDFRKQGFL-WSFSGPVAFIIFCN-AAIFVITVWKLTKKF 706
Cdd:cd15446  107 TDKLRKWVFLFIGWCIPCPII-VAWAIGKL--YYENEQCWFGKEPGKYIdYIYQGPVILVLLINfVFLFNIVRILMTKLR 183
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 251823835 707 SEINPNMKKLRKARVLTITsiaQLLVLGCTwgFGLFLFNPHSTWLS-----YIFTLLNCLQGLFLYVMLCLLNKKVR 778
Cdd:cd15446  184 ASTTSETIQYRKAVKATLV---LLPLLGIT--YMLFFVNPGEDDISqivfiYFNSFLQSFQGFFVSVFYCFLNGEVR 255
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
594-783 1.08e-09

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  Cd Length: 289  Bit Score: 60.33  E-value: 1.08e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 594 CRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAIsMAVVKmdgyghATY----CWl 669
Cdd:cd15982   95 CKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAA-WAVVR------ATLadarCW- 166
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 670 DFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKA-RVLTITSIAQLLVLGCTwgFGLFLFNPHS 748
Cdd:cd15982  167 ELSAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWETNAVGYDTRKQyRKLAKSTLVLVLVFGVH--YIVFVCLPHT 244
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 251823835 749 -TWLSYIFTL-----LNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15982  245 fTGLGWEIRMhcelfFNSFQGFFVSIIYCYCNGEVQTEIKK 285
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
589-783 1.15e-09

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  Cd Length: 280  Bit Score: 59.94  E-value: 1.15e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 589 EVGLRCRLVAVMLHFCFLAAFCWMALEGVELY-FLVVRVFQGQGLSTWQRCLiGYGVPLLIVAISMAVVKMDgygHATYC 667
Cdd:cd15985   82 KAAIGCRMAQVVMQYCILANHYWFFVEAVYLYkLLIGAVFSEKNYYLLYLYL-GWGTPVLFVVPWMLAKYLK---ENKEC 157
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 668 WLDFRKQGFLWSFSGPVAFIIFCNAAIFvITVWKLTkkFSEINPNMK-----KLRKARVlTITSIAqllVLGCTWGFGLF 742
Cdd:cd15985  158 WALNENMAYWWIIRIPILLASLINLLIF-MRILKVI--LSKLRANQKgyadyKLRLAKA-TLTLIP---LFGIHEVVFIF 230
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 251823835 743 LFNPHSTW-LSYI---FTL-LNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15985  231 ATDEQTTGiLRYIkvfFTLfLNSFQGFLVAVLYCFANKEVKSELLK 276
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
480-518 2.21e-09

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: 307782  Cd Length: 46  Bit Score: 55.84  E-value: 2.21e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 251823835  480 LICAFWK--AHNGNGYWDTDGCSMNGTG-----FCHCNHLTSFAIL 518
Cdd:pfam01825   1 PQCVFWDfdTGSGTGGWSTEGCELVTSSndthtVCSCNHLTSFAVL 46
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
589-786 4.52e-09

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  Cd Length: 280  Bit Score: 58.22  E-value: 4.52e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 589 EVGLRCRLVAVMLHFCFLAAFCWMALEGVELY-FLVVRVFQGQGLstWQR-CLIGYGVPLLIVaISMAVVKMdgYGHATY 666
Cdd:cd15266   82 ESSTSCRVAQVFMHYFVGANYFWLLVEGLYLHtLLVTAVLSERRL--LKKyMLIGWGTPVLFV-VPWGVAKI--LLENTG 156
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 667 CWLDFRKQGFLWSFSGPVAFIIFCNAAIFVITV----WKLtkKFSEINPNMKKLRKARVlTITSIAQL---------LVL 733
Cdd:cd15266  157 CWGRNENMGIWWIIRGPILLCITVNFYIFLKILklllSKL--KAQQMRFTDYKYRLARS-TLVLIPLLgihevvfsfITD 233
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 251823835 734 GCTWGFGLFlfnphsTWLsYIFTLLNCLQGLFLYVMLCLLNKKVREEYWK-WAC 786
Cdd:cd15266  234 EQVEGFSRH------IRL-FIQLTLSSFQGFLVAVLYCFANGEVKAELKKrWQL 280
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
592-783 5.96e-09

glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon-like peptide-1 receptor (GLP1R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor and GLP2R. GLP1R is activated by glucagon-like peptide 1 (GLP1), 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. 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: 320396  Cd Length: 279  Bit Score: 58.06  E-value: 5.96e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 592 LRCRLVAVMLHFCFLAAFCWMALEGVELY-FLVVRVFQGQGLSTWQRClIGYGVPLLIVaISMAVVKMdgYGHATYCWLD 670
Cdd:cd15268   84 LSCRLVFLLMQYCVAANYYWLLVEGVYLYtLLAFSVFSEQRIFRLYLS-IGWGVPLLFV-IPWGIVKY--LYEDEGCWTR 159
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 671 FRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFsEINPNMKKLRKARvLTITSIAQLLVLGCTWGFGLFLFNPHST- 749
Cdd:cd15268  160 NSNMNYWLIIRLPILFAIGVNFLIFIRVICIVISKL-KANLMCKTDIKCR-LAKSTLTLIPLLGTHEVIFAFVMDEHARg 237
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 251823835 750 WLSYI--FTLLN--CLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15268  238 TLRFVklFTELSftSFQGLMVAILYCFVNNEVQMEFRK 275
EGF_CA smart00179
Calcium-binding EGF-like domain;
214-246 9.33e-09

Calcium-binding EGF-like domain;


Pssm-ID: 214542  Cd Length: 39  Bit Score: 53.79  E-value: 9.33e-09
                           10        20        30
                   ....*....|....*....|....*....|...
gi 251823835   214 DVDECSSGqHQCHNSTVCKNTVGSYKCHCRPGW 246
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGY 32
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
594-780 9.63e-09

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  Cd Length: 268  Bit Score: 57.11  E-value: 9.63e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 594 CRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVaISMAVVKMdgYGHATYCWLDFRK 673
Cdd:cd15270   77 CKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCT-GTWILCKL--YFEDTECWDINND 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 674 QGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTwgFGLFLFNPHSTWLS- 752
Cdd:cd15270  154 SPYWWIIKGPIVISVGVNFLLFLNIIRILLKKLDPRQINFNNSAQYRRLSKSTLLLIPLFGTH--YIIFNFLPDYAGLGi 231
                        170       180       190
                 ....*....|....*....|....*....|
gi 251823835 753 --YIFTLLNCLQGLFLYVMLCLLNKKVREE 780
Cdd:cd15270  232 rlYLELCLGSFQGFIVAVLYCFLNQEVQTE 261
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
565-772 1.07e-08

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: 320095  Cd Length: 270  Bit Score: 57.03  E-value: 1.07e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 565 HLHLCICLFLGSIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLI---- 640
Cdd:cd14964   44 DLLFSLVVVPFLLLGLLSGEWSFGFAG--CKLVLFFFYLFGFASIFLLTAMAIDRYLAICHPLKYTVLMTPRRARLlilg 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 641 ------GYGVPLLIVAISMAVVKMDGYGHATYCWLDFRKQGFLW-----SFSGPVAFIIFCNAAIfVITVWKLTKKFSEI 709
Cdd:cd14964  122 iwvlslLLSLPPLLGWGTLPFCGPNVPLLTLSCSDTAWNIAYTLgllilGFLLPLLLILVSYARI-VRALLRRKRITRSA 200
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 251823835 710 NPNMKKLRKArvlTITSIAQLLVLGCTWGFGLFLfnphstWLSYIFTLLNCLQGLFLYVMLCL 772
Cdd:cd14964  201 ISSARRERKA---FKTLLIVVLVFLLCWLPYHIV------YLLPALLQLSNSLPLLLLLSVLL 254
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
555-780 1.75e-08

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


Pssm-ID: 320401  Cd Length: 285  Bit Score: 56.61  E-value: 1.75e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 555 KPIQSSRTMVHLHLCICLFLGSIIFLV---------------GVENEGGEVGLR-------CRLVAVMLHFCFLAAFCWM 612
Cdd:cd15273   30 KKLHCARNKLHMHLFASFILRAFMTLLkdslfidglglladiVERNGGGNEVIAnigsnwvCKAITSLWQYFIIANYSWI 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 613 ALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVaISMAVVKMDgyGHATYCWLDFRKQGFLWSFSGPVAFIIFCNA 692
Cdd:cd15273  110 LMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFV-VPWIVARIL--FENSLCWTTNSNLLNFLIIRIPIMISVLINF 186
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 693 AIFVITVW----KLTKKFSEINPNMKKLRKARVL---------TITSIAQLLVLGCTWGFGLFLFNPHstwlsyiftLLN 759
Cdd:cd15273  187 ILFLNIVRvllvKLRSSVNEDSRRYKKWAKSTLVlvplfgvhyTIFLILSYLDDTNEAVELIWLFCDQ---------LFA 257
                        250       260
                 ....*....|....*....|.
gi 251823835 760 CLQGLFLYVMLCLLNKKVREE 780
Cdd:cd15273  258 SFQGFFVALLYCFLNGEVRAE 278
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
594-786 3.13e-08

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, brainstem and regions containing large pyramidal cells, yets 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  Cd Length: 275  Bit Score: 55.73  E-value: 3.13e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 594 CRLVAVMLHFCFLAAFCWMALEGVELYFLVVR---VFQGQGLSTWQR------CLIGYGVPLLIVAISmAVVKMDGYG-- 662
Cdd:cd16000   70 CQAVGIVLHYSTLSTMLWIGVTARNIYKQVTKkphLCQDTDQPPYPKqpllrfYLVSGGVPFIICGIT-AATNINNYGte 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 663 --HATYCWLDFRKQgfLWSFSGPVAFIIFCNAAIFVITVWKLtKKFSEINPNMKKLRKARVLTITSIAQLLVLGCTWGFG 740
Cdd:cd16000  149 deDTPYCWMAWEPS--LGAFYGPVAFIVLVTCIYFLCTYVQL-RRHPERKYELKNEHSFKAQLRAAAFTLFLFTATWAFG 225
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 251823835 741 LFLFNpHSTWLSYIFTllnCLQGLF-----LYVMLCLLNKkvREEYWK--WAC 786
Cdd:cd16000  226 ALAVS-QGHFLDMIFS---CLYGAFcvtlgLFILIHHCAK--RDDVWHcwWSC 272
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
214-246 3.51e-08

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 52.25  E-value: 3.51e-08
                         10        20        30
                 ....*....|....*....|....*....|...
gi 251823835 214 DVDECSSGqHQCHNSTVCKNTVGSYKCHCRPGW 246
Cdd:cd00054    1 DIDECASG-NPCQNGGTCVNTVGSYRCSCPPGY 32
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
561-783 4.38e-08

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


Pssm-ID: 320393  Cd Length: 289  Bit Score: 55.46  E-value: 4.38e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 561 RTMVHLHL---------CICLF--------LGSIIFLVGVENEGGEVGLR---------CRLVAVMLHFcFLAA-FCWMA 613
Cdd:cd15265   36 RNYIHMHLfvsfmlravSIFVKdavlysgsGLDELERPSMEDLKSIVEAPpvdksqyvgCKVAVTLFLY-FLATnYYWIL 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 614 LEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAISMAV-VKMDGyghaTYCWlDFRKQGFLWSFSGPVAFIIFCNA 692
Cdd:cd15265  115 VEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVFVIPWASVrATLAD----TRCW-DLSAGNYKWIYQVPILAAIVVNF 189
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 693 AIFVITVWKLTKKFSEINPNMKKLRKA-RVLTITSIAQLLVLGCTwgFGLFLFNPHST----W-LSYIFTLL-NCLQGLF 765
Cdd:cd15265  190 ILFLNIVRVLATKLRETNAGRCDTRQQyRKLAKSTLVLIPLFGVH--YIVFMGMPYTEvgllWqIRMHYELFfNSFQGFF 267
                        250
                 ....*....|....*...
gi 251823835 766 LYVMLCLLNKKVREEYWK 783
Cdd:cd15265  268 VAIIYCFCNGEVQAEIKK 285
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
528-785 6.73e-08

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  Cd Length: 290  Bit Score: 54.95  E-value: 6.73e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 528 RLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLCICLFLGSI-IF----------------LVGVE------ 584
Cdd:cd15984    3 RLYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVsIFvkdavlysgsaleemeRITEEdlksit 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 585 -----NEGGEVGlrCRlVAVMLHFCFLAA-FCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAISMAVVKM 658
Cdd:cd15984   83 eappaDKAQFVG--CK-VAVTFFLYFLATnYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVRAT 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 659 DGyghATYCWlDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKA-RVLTITSIAQLLVLGCTw 737
Cdd:cd15984  160 LA---DTGCW-DLSAGNLKWIIQVPILAAIVVNFILFINIVRVLATKLRETNAGRCDTRQQyRKLLKSTLVLMPLFGVH- 234
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 251823835 738 gFGLFLFNPHsTWLSYIF--------TLLNCLQGLFLYVMLCLLNKKVREEYWK-WA 785
Cdd:cd15984  235 -YIVFMAMPY-TEVSGILwqvqmhyeMLFNSFQGFFVAIIYCFCNGEVQAEIKKsWS 289
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
591-780 1.22e-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  Cd Length: 270  Bit Score: 53.60  E-value: 1.22e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 591 GLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRClIGYGVPLLIVAIsMAVVKMDGYGHAtyCWLd 670
Cdd:cd15262   79 AVVCRLLSIFERAARNAVFACMFVEGFYLHRLIVAVFAEKSSIRFLYV-IGAVLPLFPVII-WAIIRALHNDHS--CWV- 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 671 FRKQGFLWSFSGPVAFIIFCNAAIFV--ITVWKLTKKFSEINPNMKKLRKARVLTI--------TSIAQLLVLGCTWgfg 740
Cdd:cd15262  154 VDIEGVQWVLDTPRLFILLVNTVLLVdiIRVLVTKLRNTEENSQTKSTTRATLFLVplfglhfvITAYRPSTDDCDW--- 230
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 251823835 741 lflfnphSTWLSYIFTLLNCLQGLFLYVMLCLLNKKVREE 780
Cdd:cd15262  231 -------EDIYYYANYLIEGLQGFLVAILFCYINKEVHYL 263
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
557-786 2.87e-07

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  Cd Length: 268  Bit Score: 52.65  E-value: 2.87e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVH--LHLCICLFLGSIIFLVGVENEGGEvgLRCRLVAVMLHFCFLAAFCWMALEGVELYF-LVVRVFQGQGLS 633
Cdd:cd15998   33 IHVSRKGWHmlLNLCFHIAMTSAVFAGGITLTNYQ--MVCQAVGITLHYSSLSTLLWMGVKARVLHKeLTWRAPPPQEGD 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRC--------LIGYGVPLLIVAISMAVVKMDGYGHATYCWLDFRKQgfLWSFSGPVAFIIFCNAAIFVITVWKLTKK 705
Cdd:cd15998  111 PALPTprpmlrfyLIAGGIPLIICGITAAVNIHNYRDHSPYCWLVWRPS--LGAFYIPVALILLVTWIYFLCAGLHLRGP 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 706 FSEINPNMKKLRKARVLTITSIAQLLVlgctWGFGLFLFNphSTWLSYIftLLNCLQ-------GLFLYVMLCLLNKKVR 778
Cdd:cd15998  189 SADGDSVYSPGVQLGALVTTHFLYLAM----WACGALAVS--QRWLPRV--VCSCLYgvaasalGLFVFTHHCARRRDVR 260

                 ....*...
gi 251823835 779 EEyWKWAC 786
Cdd:cd15998  261 AS-WRACC 267
7tmE_cAMP_R_Slime_mold cd14940
slime mold cyclic AMP receptor, member of the class E family of seven-transmembrane G ...
562-765 1.02e-06

slime mold cyclic AMP receptor, member of the class E family of seven-transmembrane G protein-coupled receptors; This family represents the class E of seven-transmembrane G-protein coupled receptors found in soil-living amoebas, commonly referred to as slime molds. The class E family includes cAMP receptors (cAR1-4) and cAMP receptors-like proteins (CrlA-C) from Dictyostelium discoideum, and their highly homologous cAMP receptors (TasA and TasB) from Polysphondylium pallidum. So far, four subtypes of cAMP receptors (cAR1-4) have been identified that play an essential role in the detection and transmit of the periodic extracellular cAMP waves that regulate chemotactic cell movement during Dictyostelium development, from the unicellular amoeba aggregate into many multicellular slugs and then differentiate into a sporocarp, a fruiting body with cells specialized for different functions. These four subtypes differ in their expression levels and patterns during development. cAR1 is high-affinity receptor that is the first one to be expressed highly during early aggregation and continues to be expressed at low levels during later developmental stages. cAR1 detects extracellular cAMP and is coupled to G-alpha2 protein. Cells lacking cAR1 fail to aggregate, demonstrating that cAR1 is responsible for aggregation. During later aggregation the high-affinity cAR3 receptor is expressed at low levels. Nonetheless, cells lacking cAR3 do not show an obviously altered pattern of development and are still able to aggregate into fruiting bodies. In contrast, cAR2 and cAR4 are low affinity receptors expressed predominantly after aggregation in pre-stalk cells. cAR2 is essential for normal tip formation and deletion of the receptor arrests development at the mound stage. On the other hand, CAR4 regulates axial patterning and cellular differentiation, and deletion of the receptor results in defects during culmination. Furthermore, three cAMP receptor-like proteins (CrlA-C) were identified in Dictyostelium that show limited sequence similarity to the cAMP receptors. Of these CrlA is thought to be required for normal cell growth and tip formation in developing aggregates.


Pssm-ID: 320094  Cd Length: 256  Bit Score: 50.81  E-value: 1.02e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 562 TMVHLHLCICLFLGSIIFLVG-VENEGGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFQGQGLSTWQRCLI 640
Cdd:cd14940   35 TRVISCFCLTSLLKDIIYTMLtLTQSARPDGFLCYLYAIVITYGSLSCWLWTLCLAISIYLLIVKREPEPEKFEKYYHFV 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 641 GYGVPLLIVAISMAVvkmDGYGHA-TYCWLDFRKQGFLWS-FSGPVAFIIFCNAAIFVITVWKLTKKFSeinpNMKKLRK 718
Cdd:cd14940  115 CWGLPLISTIIMLIK---HHYGPVgNWCWIGNQYTGYRFGlFYGPFFIIFGISAVLVGLTSHYTYQVIH----NWVSDNK 187
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 251823835 719 ARVLT--ITSIAQLLVLGCTWGFGLF-----LFNPHSTWLSYIFTLLNCLQGLF 765
Cdd:cd14940  188 DLHKTyqFKLVNYIIVFLLCWIFAVInriqnALNPFPFALNLLHTYLSPSHGFY 241
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
557-696 1.05e-06

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: 51.40  E-value: 1.05e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 557 IQSSRTMVHL--HLCICLFLGSIIFLVGV-ENEGGEVglrCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRvfqgqgls 633
Cdd:cd15999   33 VRISRKSWHMlvNLCFHIFLTCAVFVGGInQTRNASV---CQAVGIILHYSTLATVLWVGVTARNIYKQVTR-------- 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 634 TWQRC-----------------LIGYGVPLLIVAISmAVVKMDGYG---HATYCWLDFRKQgfLWSFSGPVAFIIFCNAA 693
Cdd:cd15999  102 KAKRCqdpdeppppprpmlrfyLIGGGIPIIVCGIT-AAANIKNYGsrpNAPYCWMAWEPS--LGAFYGPAGFIIFVNCM 178

                 ...
gi 251823835 694 IFV 696
Cdd:cd15999  179 YFL 181
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
528-783 2.02e-06

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


Pssm-ID: 320649  Cd Length: 285  Bit Score: 50.31  E-value: 2.02e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 528 RLELITKVGLLLSLICLLLCILTFLLVKPIQSSRTMVHLHLC---IC----LFLGSIIfLVGVENEG--------GEVGL 592
Cdd:cd15983    3 RLHLMYTIGYSISLAALLVAVCILCYFKRLHCTRNYIHIHLFasfICragsIFVKDAV-LYSGTNEGealdekieFGLSP 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 593 RCRL------VAVMLHFCFLAA-FCWMALEGVELYFLVVRVFQGQGLSTWQRCLIGYGVPLLIVAI--SMAVVKMDgygh 663
Cdd:cd15983   82 GTRLqwvgckVTVTLFLYFLATnHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVwaSVRVSLAD---- 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 664 aTYCWlDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTKKFSEINPNMKKLRKARVLTITSIAQLLVLgctwgFG--- 740
Cdd:cd15983  158 -TQCW-DLSAGNLKWIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKLDPRQQYRKLLKSTLVLMPL-----FGvhy 230
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 251823835 741 -LFLFNPHSTWLSYIF-------TLLNCLQGLFLYVMLCLLNKKVREEYWK 783
Cdd:cd15983  231 vLFMAMPYTDVTGLLWqiqmhyeMLFNSSQGFFVAFIYCFCNGEVQAEIKK 281
7tm_classA_rhodopsin-like cd00637
rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor ...
568-773 2.50e-06

rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor superfamily; Class A rhodopsin-like receptors constitute about 90% of all GPCRs. The class A GPCRs include the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands. All GPCRs have 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. Based on sequence similarity, GPCRs can be divided into six major classes: class A (rhodopsin-like family), class B (Methuselah-like, adhesion and secretin-like receptor family), class C (metabotropic glutamate receptor family), class D (fungal mating pheromone receptors), class E (cAMP receptor family), and class F (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: 320086  Cd Length: 274  Bit Score: 49.97  E-value: 2.50e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 568 LCICLFLG--SIIFLVGVENEGGEVGlrCRLVAVMLHFCFLAA---FCWMAlegVELYFLVVRVFQGQGLSTWQRCLIG- 641
Cdd:cd00637   45 LLVGLLVIpfSLVSLLLGGWWFGDAL--CKLLGFLQTVSLTASiltLTAIS---VDRYLAIVHPLRYRRRFTKRRAKLVi 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 642 ---YGVPLLIVAISMAVVKMDGYGHATYCWLDFRKQG---------FLWSFSGPVAFIIFCNAAIFvITVWKLTKKFSEI 709
Cdd:cd00637  120 aliWLLSLLLALPPLLGWKVYEYGGYCCCCLCWPDLTlskaytiflFVLLFLLPLLVIIVCYVRIF-RKLRRHRKRISSS 198
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 251823835 710 NPNMKKLRKARV--LTITSIAQLLVLGCTWGfglflfnP-HSTWLSYIFTLLNCLQGLFLYVMLCLL 773
Cdd:cd00637  199 SNSSRRRRRRRErkVTKMLLIVVVVFLLCWL-------PyFILFLLDVFGPDPSPLPRILYFLALLL 258
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
560-780 4.75e-06

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  Cd Length: 269  Bit Score: 49.03  E-value: 4.75e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 560 SRTMVHLHLCICLFLGSIIFLV----------GVENEGGEVGLRCRLVAVMLHFCFLAAFCWMALEGVELYFLVVRVFqg 629
Cdd:cd15986   35 TRNYIHLNLFFSFILRAISVLVkddilysssnTEHCTVPPSLIGCKVSLVILQYCIMANFYWLLVEGLYLHTLLVVIF-- 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 630 qglsTWQRC-----LIGYGVPLLIVaISMAVVKMdgYGHATYCWLDFRKQGFLWSFSGPVAFIIFCNAAIFVITVWKLTK 704
Cdd:cd15986  113 ----SENRHfivylLIGWGIPTVFI-IAWIVARI--YLEDTGCWDTNDHSVPWWVIRIPIIISIILNFILFISIIRILLQ 185
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 251823835 705 KFS--EINPN----MKKLRKARVLTITsiaqllVLGCTWGFGLFLFNPHSTWLSYIFTL-LNCLQGLFLYVMLCLLNKKV 777
Cdd:cd15986  186 KLRspDVGGNdqsqYKRLAKSTLLLIP------LFGVHYIVFVYFPDSSSSNYQIFFELcLGSFQGLVVAILYCFLNSEV 259

                 ...
gi 251823835 778 REE 780
Cdd:cd15986  260 QGE 262
EGF_CA smart00179
Calcium-binding EGF-like domain;
165-197 8.71e-06

Calcium-binding EGF-like domain;


Pssm-ID: 214542  Cd Length: 39  Bit Score: 45.32  E-value: 8.71e-06
                           10        20        30
                   ....*....|....*....|....*....|...
gi 251823835   165 DVNECISGqNHCHQSTHCINKLGGYSCICRQGW 197
Cdd:smart00179   1 DIDECASG-NPCQNGGTCVNTVGSYRCECPPGY 32
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
478-522 1.25e-05

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: 44.69  E-value: 1.25e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 251823835   478 HELICAFWKahNGNGYWDTDGCSM----NGTGFCHCNHLTSFAILMAQY 522
Cdd:smart00303   1 FNPICVFWD--ESSGEWSTRGCELletnGTHTTCSCNHLTTFAVLMDVP 47
EGF_CA pfam07645
Calcium-binding EGF domain;
69-118 3.73e-05

Calcium-binding EGF domain;


Pssm-ID: 311536  Cd Length: 42  Bit Score: 43.50  E-value: 3.73e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 251823835   69 DINECLLPGFSCGDFAMCKNSEGSYTCVCNLGYKllsgaesfVNESENTC 118
Cdd:pfam07645   1 DVDECADGTHNCPANTVCVNTIGSFECVCPDGYE--------NNEDGTNC 42
EGF_CA smart00179
Calcium-binding EGF-like domain;
69-101 4.61e-05

Calcium-binding EGF-like domain;


Pssm-ID: 214542  Cd Length: 39  Bit Score: 43.00  E-value: 4.61e-05
                           10        20        30
                   ....*....|....*....|....*....|...
gi 251823835    69 DINECLLPGfSCGDFAMCKNSEGSYTCVCNLGY 101
Cdd:smart00179   1 DIDECASGN-PCQNGGTCVNTVGSYRCECPPGY 32
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
69-103 8.34e-05

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 42.24  E-value: 8.34e-05
                         10        20        30
                 ....*....|....*....|....*....|....*
gi 251823835  69 DINECLLPGfSCGDFAMCKNSEGSYTCVCNLGYKL 103
Cdd:cd00054    1 DIDECASGN-PCQNGGTCVNTVGSYRCSCPPGYTG 34
EGF_CA cd00054
Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular ...
165-197 8.83e-05

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.


Pssm-ID: 238011  Cd Length: 38  Bit Score: 42.24  E-value: 8.83e-05
                         10        20        30
                 ....*....|....*....|....*....|...
gi 251823835 165 DVNECISGqNHCHQSTHCINKLGGYSCICRQGW 197
Cdd:cd00054    1 DIDECASG-NPCQNGGTCVNTVGSYRCSCPPGY 32
EGF cd00053
Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large ...
217-246 3.46e-04

Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large number of proteins, mostly animal; the list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied; the functional significance of EGF-like domains in what appear to be unrelated proteins is not yet clear; a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase); the domain includes six cysteine residues which have been shown to be involved in disulfide bonds; the main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet; Subdomains between the conserved cysteines vary in length; the region between the 5th and 6th cysteine contains two conserved glycines of which at least one is present in most EGF-like domains; a subset of these bind calcium.


Pssm-ID: 238010  Cd Length: 36  Bit Score: 40.54  E-value: 3.46e-04
                         10        20        30
                 ....*....|....*....|....*....|
gi 251823835 217 ECSSgQHQCHNSTVCKNTVGSYKCHCRPGW 246
Cdd:cd00053    1 ECAA-SNPCSNGGTCV