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Conserved domains on  [gi|530381549|ref|XP_005248949|]
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adhesion G protein-coupled receptor F5 isoform X1 [Homo sapiens]

Protein Classification

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List of domain hits

Name Accession Description Interval E-value
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
1049-1323 1.86e-173

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


:

Pssm-ID: 320382 [Multi-domain]  Cd Length: 275  Bit Score: 516.66  E-value: 1.86e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1049 GILLDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLVANTWFIVVAAIQDNRYILCKTACVA 1128
Cdd:cd15254     1 LDELDYITYIGLSISILSLAICIVIESLVWKSVTKNRTSYMRHVCILNIAVSLLIADIWFIVVAAIQDQNYAVNGNVCVA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1129 ATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFCLGYGCPLAISVITLGATQPREVYTRKNVCWLNWED 1208
Cdd:cd15254    81 ATFFIHFFYLCVFFWMLALGLMLFYRLVFILHDTSKTIQKAVAFCLGYGCPLIISVITIAVTLPRDSYTRKKVCWLNWED 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1209 TKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTNLVFH 1288
Cdd:cd15254   161 SKALLAFVIPALIIVAVNSIITVVVIVKILRPSIGEKPSKQERSSLFQIIKSIGVLTPLLGLTWGFGLATVIKGSSIVFH 240
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 530381549 1289 IIFAILNVFQGLFILLFGCLWDLKVQEALLNKFSL 1323
Cdd:cd15254   241 ILFTLLNAFQGLFILVFGTLWDKKVQEALLNKYSF 275
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
993-1036 6.14e-15

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


:

Pssm-ID: 460350  Cd Length: 44  Bit Score: 70.03  E-value: 6.14e-15
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 530381549   993 KCVFWNFrLANNTGGWDSSGCYVEEGDGDNVTCICDHLTSFSIL 1036
Cdd:pfam01825    2 QCVFWDF-TNSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
285-361 1.06e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


:

Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.58  E-value: 1.06e-07
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530381549    285 EGDTVSLVCE-KEVLSSNVSWRYEEQQLeIQNSSRFSIytalfNNMTSVSKLTIHNITPGDAGEYVCKLILDIFEYEC 361
Cdd:smart00410    8 EGESVTLSCEaSGSPPPEVTWYKQGGKL-LAESGRFSV-----SRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79
SEA super family cl02507
SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed ...
179-281 1.24e-05

SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed function of regulating or binding carbohydrate side chains. Recently a proteolytic activity has been shown for a SEA domain.


The actual alignment was detected with superfamily member smart00200:

Pssm-ID: 470595  Cd Length: 121  Bit Score: 45.87  E-value: 1.24e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549    179 NVGFQEDLMNTSSALYRSYKTDLETAFRKGYG---ILPGFKGVTVTGFKSGSVVVTYEVKTTPPSleliHKANEQVVQSL 255
Cdd:smart00200   18 NLQYSPSLEDPSSEEYQELVRDVEKLLEQIYGktdLKPDFVGTEVIEFRNGSVVVDLGLLFNEGV----TNGQDVEEDLL 93
                            90       100
                    ....*....|....*....|....*..
gi 530381549    256 NQTYKMDYNS-FQAVTINESNFFVTPE 281
Cdd:smart00200   94 QVIKQAAYSLkITNVNVVDVLDPDSAD 120
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
517-602 7.94e-04

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


:

Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 39.80  E-value: 7.94e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549    517 PDPISVSEGQNFSIKCISDVSNYDEVYWNTSAGIKIYQRFYTTRRYlDGAESVLTVKTSTREWNGTYHCIFRYKNSYSIA 596
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSR-SGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                    ....*.
gi 530381549    597 TKDVIV 602
Cdd:smart00410   80 GTTLTV 85
 
Name Accession Description Interval E-value
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
1049-1323 1.86e-173

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


Pssm-ID: 320382 [Multi-domain]  Cd Length: 275  Bit Score: 516.66  E-value: 1.86e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1049 GILLDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLVANTWFIVVAAIQDNRYILCKTACVA 1128
Cdd:cd15254     1 LDELDYITYIGLSISILSLAICIVIESLVWKSVTKNRTSYMRHVCILNIAVSLLIADIWFIVVAAIQDQNYAVNGNVCVA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1129 ATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFCLGYGCPLAISVITLGATQPREVYTRKNVCWLNWED 1208
Cdd:cd15254    81 ATFFIHFFYLCVFFWMLALGLMLFYRLVFILHDTSKTIQKAVAFCLGYGCPLIISVITIAVTLPRDSYTRKKVCWLNWED 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1209 TKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTNLVFH 1288
Cdd:cd15254   161 SKALLAFVIPALIIVAVNSIITVVVIVKILRPSIGEKPSKQERSSLFQIIKSIGVLTPLLGLTWGFGLATVIKGSSIVFH 240
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 530381549 1289 IIFAILNVFQGLFILLFGCLWDLKVQEALLNKFSL 1323
Cdd:cd15254   241 ILFTLLNAFQGLFILVFGTLWDKKVQEALLNKYSF 275
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
1051-1302 5.44e-34

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 131.63  E-value: 5.44e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549  1051 LLDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVVAAIQDNRYILCKT---ACV 1127
Cdd:pfam00002    3 SLKVIYTVGYSLSLVALLLAIAIFLLF-RKLHCTRNYIHLNLFA-----SFILRALLFLVGDAVLFNKQDLDHCswvGCK 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549  1128 AATFFIHFFYLSVFFWMLTLGLMLfYRLVFILHETSRSTQKAIaFCLGYGCPLAIsVITLGATQPREVYTRKNvCWLNwE 1207
Cdd:pfam00002   77 VVAVFLHYFFLANFFWMLVEGLYL-YTLLVEVFFSERKYFWWY-LLIGWGVPALV-VGIWAGVDPKGYGEDDG-CWLS-N 151
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549  1208 DTKALLAFAIPALIIVVVNI---TITIVVITKILRPSigdKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTN 1284
Cdd:pfam00002  152 ENGLWWIIRGPILLIILVNFiifINIVRILVQKLRET---NMGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFAFNPENT 228
                          250       260
                   ....*....|....*....|
gi 530381549  1285 L--VFHIIFAILNVFQGLFI 1302
Cdd:pfam00002  229 LrvVFLYLFLILNSFQGFFV 248
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
993-1036 6.14e-15

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


Pssm-ID: 460350  Cd Length: 44  Bit Score: 70.03  E-value: 6.14e-15
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 530381549   993 KCVFWNFrLANNTGGWDSSGCYVEEGDGDNVTCICDHLTSFSIL 1036
Cdd:pfam01825    2 QCVFWDF-TNSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
990-1042 2.44e-14

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: 68.18  E-value: 2.44e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 530381549    990 GETKCVFWNFRlannTGGWDSSGCYVEEGDGDNVTCICDHLTSFSILMSPDSP 1042
Cdd:smart00303    1 FNPICVFWDES----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
285-361 1.06e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.58  E-value: 1.06e-07
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530381549    285 EGDTVSLVCE-KEVLSSNVSWRYEEQQLeIQNSSRFSIytalfNNMTSVSKLTIHNITPGDAGEYVCKLILDIFEYEC 361
Cdd:smart00410    8 EGESVTLSCEaSGSPPPEVTWYKQGGKL-LAESGRFSV-----SRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79
SEA smart00200
Domain found in sea urchin sperm protein, enterokinase, agrin; Proposed function of regulating ...
179-281 1.24e-05

Domain found in sea urchin sperm protein, enterokinase, agrin; Proposed function of regulating or binding carbohydrate sidechains.


Pssm-ID: 214554  Cd Length: 121  Bit Score: 45.87  E-value: 1.24e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549    179 NVGFQEDLMNTSSALYRSYKTDLETAFRKGYG---ILPGFKGVTVTGFKSGSVVVTYEVKTTPPSleliHKANEQVVQSL 255
Cdd:smart00200   18 NLQYSPSLEDPSSEEYQELVRDVEKLLEQIYGktdLKPDFVGTEVIEFRNGSVVVDLGLLFNEGV----TNGQDVEEDLL 93
                            90       100
                    ....*....|....*....|....*..
gi 530381549    256 NQTYKMDYNS-FQAVTINESNFFVTPE 281
Cdd:smart00200   94 QVIKQAAYSLkITNVNVVDVLDPDSAD 120
SEA pfam01390
SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed ...
170-258 2.66e-05

SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed function of regulating or binding carbohydrate side chains. Recently a proteolytic activity has been shown for a SEA domain.


Pssm-ID: 460188  Cd Length: 100  Bit Score: 44.54  E-value: 2.66e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549   170 VTLNMRVrLNVGFQEDLMNTSSALYRSYKTDLETAFRKGY---GILPGFKGVTVTGFKS--GSVVVTYEVKTTPPSLELi 244
Cdd:pfam01390    3 YTGSFKI-TNLQYTPDLGNPSSQEFKSLSRRIESLLNELFrnsSLRKQYIKSHVLRLRPdgGSVVVDVVLVFRFPSTEP- 80
                           90
                   ....*....|....*
gi 530381549   245 HKANEQVVQS-LNQT 258
Cdd:pfam01390   81 ALDREKLIEEiLRQT 95
I-set pfam07679
Immunoglobulin I-set domain;
285-351 4.11e-05

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 43.40  E-value: 4.11e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530381549   285 EGDTVSLVCE-KEVLSSNVSWRYEEQqlEIQNSSRFSIytalfNNMTSVSKLTIHNITPGDAGEYVCK 351
Cdd:pfam07679   14 EGESARFTCTvTGTPDPEVSWFKDGQ--PLRSSDRFKV-----TYEGGTYTLTISNVQPDDSGKYTCV 74
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
517-602 7.94e-04

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 39.80  E-value: 7.94e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549    517 PDPISVSEGQNFSIKCISDVSNYDEVYWNTSAGIKIYQRFYTTRRYlDGAESVLTVKTSTREWNGTYHCIFRYKNSYSIA 596
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSR-SGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                    ....*.
gi 530381549    597 TKDVIV 602
Cdd:smart00410   80 GTTLTV 85
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
513-586 1.19e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 39.09  E-value: 1.19e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530381549   513 LTITPDPISVSEGQNFSIKCISDVSNYDEVYWNTSAGIKIYQRfyTTRRYLDGAESVLTVKTSTREWNGTYHCI 586
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGS--TRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
289-351 5.09e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 36.92  E-value: 5.09e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530381549  289 VSLVCE-KEVLSSNVSWRYEEQQLEIQNSSRFSIYTalfnnmtSVSKLTIHNITPGDAGEYVCK 351
Cdd:cd00096     1 VTLTCSaSGNPPPTITWYKNGKPLPPSSRDSRRSEL-------GNGTLTISNVTLEDSGTYTCV 57
 
Name Accession Description Interval E-value
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
1049-1323 1.86e-173

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


Pssm-ID: 320382 [Multi-domain]  Cd Length: 275  Bit Score: 516.66  E-value: 1.86e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1049 GILLDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLVANTWFIVVAAIQDNRYILCKTACVA 1128
Cdd:cd15254     1 LDELDYITYIGLSISILSLAICIVIESLVWKSVTKNRTSYMRHVCILNIAVSLLIADIWFIVVAAIQDQNYAVNGNVCVA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1129 ATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFCLGYGCPLAISVITLGATQPREVYTRKNVCWLNWED 1208
Cdd:cd15254    81 ATFFIHFFYLCVFFWMLALGLMLFYRLVFILHDTSKTIQKAVAFCLGYGCPLIISVITIAVTLPRDSYTRKKVCWLNWED 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1209 TKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTNLVFH 1288
Cdd:cd15254   161 SKALLAFVIPALIIVAVNSIITVVVIVKILRPSIGEKPSKQERSSLFQIIKSIGVLTPLLGLTWGFGLATVIKGSSIVFH 240
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 530381549 1289 IIFAILNVFQGLFILLFGCLWDLKVQEALLNKFSL 1323
Cdd:cd15254   241 ILFTLLNAFQGLFILVFGTLWDKKVQEALLNKYSF 275
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
1049-1318 2.45e-161

orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group VI adhesion GPCRs consist of orphan receptors GPR110, GPR111, GPR113, GPR115, GPR116, and closely related proteins. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. GPR110 possesses a SEA box in the N-terminal has been identified as an oncogene over-expressed in lung and prostate cancer. GPR113 contains a hormone binding domain and one EGF (epidermal grown factor) domain. GPR112 has extremely long N-terminus (about 2,400 amino acids) containing a number of Ser/Thr-rich glycosylation sites and a pentraxin (PTX) domain. GPR116 has two C2-set immunoglobulin-like repeats, which is found in the members of the immunoglobulin superfamily of cell surface proteins, and a SEA (sea urchin sperm protein, enterokinase, and a grin)-box, which is present in the extracellular domain of the transmembrane mucin (MUC) family and known to enhance O-glycosylation. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320598 [Multi-domain]  Cd Length: 268  Bit Score: 484.89  E-value: 2.45e-161
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1049 GILLDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLVANTWFIVVAAIQDNRYilCKTACVA 1128
Cdd:cd15932     1 SPALDYITYVGLGISILSLVLCLIIEALVWKSVTKNKTSYMRHVCLVNIALSLLIADIWFIIGAAISTPPN--PSPACTA 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1129 ATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFCLGYGCPLAISVITLGATQPREVYTRKNVCWLNWED 1208
Cdd:cd15932    79 ATFFIHFFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITVAATAPQGGYTRKGVCWLNWDK 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1209 TKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTNLVFH 1288
Cdd:cd15932   159 TKALLAFVIPALAIVVVNFIILIVVIFKLLRPSVGERPSKDEKNALVQIGKSVAILTPLLGLTWGFGLGTMIDPKSLAFH 238
                         250       260       270
                  ....*....|....*....|....*....|
gi 530381549 1289 IIFAILNVFQGLFILLFGCLWDLKVQEALL 1318
Cdd:cd15932   239 IIFAILNSFQGFFILVFGTLLDSKVREALL 268
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
1051-1317 4.55e-105

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


Pssm-ID: 320660 [Multi-domain]  Cd Length: 267  Bit Score: 334.11  E-value: 4.55e-105
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1051 LLDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLVANTWFIVVAAIqdNRYILCKTACVAAT 1130
Cdd:cd15994     3 VLDYITRIGLGLSIFSLALCLTIEAVVWSHVTKTEITYMRHVCIVNIATSLLIADVWFILASIV--HNTALNYPLCVAAT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1131 FFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFCLGYGCPLAISVITLGATQPREVYTRKNVCWLNWEDTK 1210
Cdd:cd15994    81 FFLHFFYLSLFFWMLTKALLILYGILLVFFKITKSVFIATAFSIGYGCPLVIAVLTVAITEPKKGYLRPEACWLNWDETK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1211 ALLAFAIPALIIVVVNITITIVVITKILRPSIGDKpCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTNLVFHII 1290
Cdd:cd15994   161 ALLAFIIPALSIVVVNLIVVGVVVVKTQRSSIGES-CKQDVSNIIRISKNVAILTPLLGLTWGFGLATIIDSRSLPFHII 239
                         250       260
                  ....*....|....*....|....*..
gi 530381549 1291 FAILNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15994   240 FALLNAFQGFFILLFGTILDRKIRIAL 266
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
1052-1322 1.01e-90

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


Pssm-ID: 320381 [Multi-domain]  Cd Length: 271  Bit Score: 294.75  E-value: 1.01e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLVANTWFIVVAAIQDNRYilcKTACVAATF 1131
Cdd:cd15253     4 LDFLSQVGLGASILALLLCLGIYRLVWRSVVRNKISYFRHMTLVNIAFSLLLADTCFLGATFLSAGHE---SPLCLAAAF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFCLGYGCPLAISVITLGATQPREVYTRKNVCWLNWEdTKA 1211
Cdd:cd15253    81 LCHFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVTLGYLCPLLIAAATVAYYYPKRQYLHEGACWLNGE-SGA 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1212 LLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTNLVFHIIF 1291
Cdd:cd15253   160 IYAFSIPVLAIVLVNLLVLFVVLMKLMRPSVSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLTGESSQVSHYGF 239
                         250       260       270
                  ....*....|....*....|....*....|.
gi 530381549 1292 AILNVFQGLFILLFGCLWDLKVQEALLNKFS 1322
Cdd:cd15253   240 AILNAFQGVFILLFGCLMDKKVREALLKRLC 270
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
1052-1316 3.02e-56

adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G protein-coupled receptors; The B2 subfamily of class B GPCRs consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320168 [Multi-domain]  Cd Length: 253  Bit Score: 195.87  E-value: 3.02e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTsymrhTCIVNIAASLLVANTwFIVVAAIQDNRYILCktacVAATF 1131
Cdd:cd15040     4 LSIITYIGCGLSLLGLLLTIITYILFRKLRKRKPT-----KILLNLCLALLLANL-LFLFGINSTDNPVLC----TAVAA 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKaIAFCLGYGCPLAISVITLGATqPREVYTRKNVCWLNWEDTkA 1211
Cdd:cd15040    74 LLHYFLLASFMWMLVEALLLYLRLVKVFGTYPRHFIL-KYALIGWGLPLIIVIITLAVD-PDSYGNSSGYCWLSNGNG-L 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1212 LLAFAIPALIIVVVNITITIVVITKILRPSIGDKPcKQEKSSLFQISKSIGVLtPLLGLTWGFGLTTVFpGTNLVFHIIF 1291
Cdd:cd15040   151 YYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNK-KKRKKTKAQLRAAVSLF-FLLGLTWIFGILAIF-GARVVFQYLF 227
                         250       260
                  ....*....|....*....|....*
gi 530381549 1292 AILNVFQGLFILLFGCLWDLKVQEA 1316
Cdd:cd15040   228 AIFNSLQGFFIFIFHCLRNKEVRKA 252
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
1050-1317 7.36e-51

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


Pssm-ID: 320599 [Multi-domain]  Cd Length: 252  Bit Score: 180.22  E-value: 7.36e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVeAVVWKSVTKNRtsYMRHTcivNIAASLLVANTWFivVAAIQDNRYilcKTACVAA 1129
Cdd:cd15933     2 RALSIISYIGCGISIACLALTLII-FLVLRVLSSDR--FQIHK---NLCVALLLAQILL--LAGEWAEGN---KVACKVV 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTqkaIAFCLGYGCPLAISVITLGATQprEVYTRKNVCWLNWEDt 1209
Cdd:cd15933    71 AILLHFFFMAAFSWMLVEGLHLYLMIVKVFNYKSKMR---YYYFIGWGLPAIIVAISLAILF--DDYGSPNVCWLSLDD- 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 KALLAFAIPALIIVVVNITITIVVITKILR-PSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTnLVFH 1288
Cdd:cd15933   145 GLIWAFVGPVIFIITVNTVILILVVKITVSlSTNDAKKSQGTLAQIKSTAKASVVLLPILGLTWLFGVLVVNSQT-IVFQ 223
                         250       260
                  ....*....|....*....|....*....
gi 530381549 1289 IIFAILNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15933   224 YIFVILNSLQGLMIFLFHCVLNSEVRSAF 252
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
1052-1317 2.27e-49

class B family of seven-transmembrane G protein-coupled receptors; The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.


Pssm-ID: 410627 [Multi-domain]  Cd Length: 260  Bit Score: 176.25  E-value: 2.27e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVWKSvtknRTsyMRHTCIVNIAASLLVANTWFIVVAAIQDNRYilcKTACVAATF 1131
Cdd:cd13952     4 LSIITYIGCSLSLVGLLLTIITYLLFPKL----RN--LRGKILINLCLSLLLAQLLFLIGQLLTSSDR---PVLCKALAI 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKaIAFCLGYGCPLAISVITLGATQ---PREVYTRKNVCWLNwED 1208
Cdd:cd13952    75 LLHYFLLASFFWMLVEAFDLYRTFVKVFGSSERRRFL-KYSLYGWGLPLLIVIITAIVDFslyGPSPGYGGEYCWLS-NG 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1209 TKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQIsKSIGVLTPLLGLTWGFGLTTVFPGTNLVFH 1288
Cdd:cd13952   153 NALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSDRKQL-RAYLKLFPLMGLTWIFGILAPFVGGSLVFW 231
                         250       260
                  ....*....|....*....|....*....
gi 530381549 1289 IIFAILNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd13952   232 YLFDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
1050-1320 2.88e-37

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


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 141.60  E-value: 2.88e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTcivNIAASLLVANTWFIVVAaiqdnRYILCKTACVAA 1129
Cdd:cd15256     2 VALSSITYVGCSLSIFCLAITLVTFAVLSSVSTIRNQRYHIHA---NLSFAVLVAQILLLISF-----RFEPGTLPCKIM 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILheTSRSTQKAIAFCLGYGCPLAISVITLgaTQPREVYTRKNVCWLNWEDt 1209
Cdd:cd15256    74 AILLHFFFLSAFAWMLVEGLHLYSMVIKVF--GSEESKHFYYYGIGWGSPLLICIISL--TSALDSYGESDNCWLSLEN- 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 KALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVfPGTNLVFHI 1289
Cdd:cd15256   149 GAIWAFVAPALFVIVVNIGILIAVTRVISRISADNYKVHGDANAFKLTAKAVAVLLPILGSSWVFGVLAV-NTHALVFQY 227
                         250       260       270
                  ....*....|....*....|....*....|.
gi 530381549 1290 IFAILNVFQGLFILLFGCLWDLKVQEALLNK 1320
Cdd:cd15256   228 MFAIFNSLQGFFIFLFHCLLNSEVRAAFKHK 258
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
1051-1302 5.44e-34

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 131.63  E-value: 5.44e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549  1051 LLDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVVAAIQDNRYILCKT---ACV 1127
Cdd:pfam00002    3 SLKVIYTVGYSLSLVALLLAIAIFLLF-RKLHCTRNYIHLNLFA-----SFILRALLFLVGDAVLFNKQDLDHCswvGCK 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549  1128 AATFFIHFFYLSVFFWMLTLGLMLfYRLVFILHETSRSTQKAIaFCLGYGCPLAIsVITLGATQPREVYTRKNvCWLNwE 1207
Cdd:pfam00002   77 VVAVFLHYFFLANFFWMLVEGLYL-YTLLVEVFFSERKYFWWY-LLIGWGVPALV-VGIWAGVDPKGYGEDDG-CWLS-N 151
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549  1208 DTKALLAFAIPALIIVVVNI---TITIVVITKILRPSigdKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTN 1284
Cdd:pfam00002  152 ENGLWWIIRGPILLIILVNFiifINIVRILVQKLRET---NMGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFAFNPENT 228
                          250       260
                   ....*....|....*....|
gi 530381549  1285 L--VFHIIFAILNVFQGLFI 1302
Cdd:pfam00002  229 LrvVFLYLFLILNSFQGFFV 248
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
1050-1314 9.62e-34

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


Pssm-ID: 320556 [Multi-domain]  Cd Length: 259  Bit Score: 131.23  E-value: 9.62e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYMRHTCivniaASLLVANTWFIVVAAIQDNRyILCKTACVaa 1129
Cdd:cd15440     2 SALTFITYIGCIISIVCLLLAFITFTCF-RNLQCDRNTIHKNLC-----LCLLIAEIVFLLGIDQTENR-TLCGVIAG-- 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 tfFIHFFYLSVFFWMLTLGLMLFYRL--VFilhETSRSTQKAIAFClGYGCPLAISVITLGATqpREVYTRKNVCWLNwE 1207
Cdd:cd15440    73 --LLHYFFLAAFSWMLLEGFQLYVMLveVF---EPEKSRIKWYYLF-GYGLPALIVAVSAGVD--PTGYGTEDHCWLS-T 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1208 DTKALLAFAIPALIIVVVNITITIVVITKILRPSIGDkPCKQEKSSLFQIS---KSIGVLTPLLGLTWGFGLTTVFPGTn 1284
Cdd:cd15440   144 ENGFIWSFVGPVIVVLLANLVFLGMAIYVMCRHSSRS-ASKKDASKLKNIRgwlKGSIVLVVLLGLTWTFGLLFINQES- 221
                         250       260       270
                  ....*....|....*....|....*....|
gi 530381549 1285 LVFHIIFAILNVFQGLFILLFGCLWDLKVQ 1314
Cdd:cd15440   222 IVMAYIFTILNSLQGLFIFIFHCVLNEKVR 251
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
1050-1320 5.15e-32

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


Pssm-ID: 320557 [Multi-domain]  Cd Length: 254  Bit Score: 126.21  E-value: 5.15e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYmrHTcivNIAASLLVANTWFIVVAAIQDNRYIlcktaCVAA 1129
Cdd:cd15441     2 LLLKIVTYIGIGISLVLLVIAFLVLSCL-RGLQSNSNSI--HK---NLVACLLLAELLFLLGINQTENLFP-----CKLI 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVfilhETSRSTQKAIAFC--LGYGCPLAISVITLGaTQPrEVYTRKNVCWLNWE 1207
Cdd:cd15441    71 AILLHYFYLSAFSWLLVESLHLYRMLT----EPRDINHGHMRFYylLGYGIPAIIVGLSVG-LRP-DGYGNPDFCWLSVN 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1208 DTkALLAFAIPALIIVVVNITITIVVITKILRpsigDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTnLVF 1287
Cdd:cd15441   145 ET-LIWSFAGPIAFVIVITLIIFILALRASCT----LKRHVLEKASVRTDLRSSFLLLPLLGATWVFGLLAVNEDS-ELL 218
                         250       260       270
                  ....*....|....*....|....*....|...
gi 530381549 1288 HIIFAILNVFQGLFILLFGCLWDLKVQEALLNK 1320
Cdd:cd15441   219 HYLFAGLNFLQGLFIFLFYCIFNKKVRRELKNA 251
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
1053-1307 7.85e-30

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


Pssm-ID: 410632 [Multi-domain]  Cd Length: 270  Bit Score: 120.02  E-value: 7.85e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1053 DIISYVGVGFSILSLAaCLVVEAVVWKSVTKNRTSYMRhtCIVNIAASLLVANTWFIVVAAIQDNRYilckTACVAATFF 1132
Cdd:cd15039     2 SILGILTLIGLIISLV-FLLLTLAVYALLPELRNLHGK--CLMCLVLSLFVAYLLLLIGQLLSSGDS----TLCVALGIL 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1133 IHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKA--IAFCL-GYGCPLAISVITLGATQ--PREVYTR---KNVCWL 1204
Cdd:cd15039    75 LHFFFLAAFFWLNVMSFDIWRTFRGKRSSSSRSKERKrfLRYSLyAWGVPLLLVAVTIIVDFspNTDSLRPgygEGSCWI 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1205 NwEDTKALLAFAIPALIIVVVNITITIVVITKILR-PSIGDKPCK--QEKSSLFQISKSIGVLTpllGLTWGFGLTTVFP 1281
Cdd:cd15039   155 S-NPWALLLYFYGPVALLLLFNIILFILTAIRIRKvKKETAKVQSrlRSDKQRFRLYLKLFVIM---GVTWILEIISWFV 230
                         250       260
                  ....*....|....*....|....*..
gi 530381549 1282 GTNLVFHIIFAILNVFQGLFI-LLFGC 1307
Cdd:cd15039   231 GGSSVLWYIFDILNGLQGVFIfLIFVC 257
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
1058-1317 1.19e-27

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: 113.50  E-value: 1.19e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1058 VGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLvantwfIVVAAIQdnryILCKTACVAATFFIHFFY 1137
Cdd:cd15251    10 VGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNIL------ILVGQTQ----TLNKGVCTMTAAFLHFFF 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1138 LSVFFWMLTLGLMLFyrLVFILHETSRSTQKAIaFCLGYGCPLAISVITLGATQPREvYTRKNVCWLNWEDtKALLAFAI 1217
Cdd:cd15251    80 LSSFCWVLTEAWQSY--MAVTGRMRTRLIRKRF-LCLGWGLPALVVAVSVGFTRTKG-YGTSSYCWLSLEG-GLLYAFVG 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1218 PALIIVVVNITITIVVITKIL-RPSIGDKPCKQEKSSLfqisksigVLTPLLGLTWGFGLTTVFPGTNLVFHIIFAILNV 1296
Cdd:cd15251   155 PAAAVVLVNMVIGILVFNKLVsRDGISDNAMASLWSSC--------VVLPLLALTWMSAVLAMTDRRSVLFQILFAVFDS 226
                         250       260
                  ....*....|....*....|.
gi 530381549 1297 FQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15251   227 LQGFVIVMVHCILRREVQDAV 247
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
1050-1315 8.18e-27

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


Pssm-ID: 320380 [Multi-domain]  Cd Length: 257  Bit Score: 111.06  E-value: 8.18e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAAClVVEAVVWKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVVAAIQDNryilcKTACVAA 1129
Cdd:cd15252     2 NILTRITQVGIIISLVCLAIC-IFTFWFFRGLQSDRTTIHKNLCI-----SLFLAELVFLIGINTTTN-----KIFCSVI 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILhETSRSTQKAIAFcLGYGCPLAIsVITLGATQPREVYTRKnVCWLNwEDT 1209
Cdd:cd15252    71 AGLLHYFFLAAFAWMFIEGIQLYLMLVEVF-ENEGSRHKNFYI-FGYGSPAVI-VGVSAALGYRYYGTTK-VCWLS-TEN 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 KALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTnLVFHI 1289
Cdd:cd15252   146 YFIWSFIGPATLIILLNLIFLGVAIYKMFRHTAGLKPEVSCLENIRSWARGAIALLFLLGLTWIFGVLHINHAS-VVMAY 224
                         250       260
                  ....*....|....*....|....*.
gi 530381549 1290 IFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd15252   225 LFTVSNSLQGMFIFLFHCVLSRKVRK 250
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
1052-1315 2.90e-26

CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the leukocyte cell-surface antigen CD97 and the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4), are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily B2 of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying numbers of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of CD97, alternative splicing results in three isoforms possessing either three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. For example, CD97, which is involved in angiogenesis and the migration and invasion of tumor cells, has been shown to promote cell aggregation in a GPS proteolysis-dependent manner. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320554 [Multi-domain]  Cd Length: 261  Bit Score: 109.47  E-value: 2.90e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVVAAIQDNryilcKTACVAATF 1131
Cdd:cd15438     4 LTLITKVGLSVSLFCLFLCILTFLFC-RSIRGTRNTIHLHLCL-----SLFLAHLIFLLGINNTNN-----QVACAVVAG 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFclGYGCPLAISVITlgATQPREVYTRKNVCWLNWEDTkA 1211
Cdd:cd15438    73 LLHYFFLAAFCWMSLEGVELYLMVVQVFNTQSLKKRYLLLI--GYGVPLVIVAIS--AAVNSKGYGTQRHCWLSLERG-F 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1212 LLAFAIPALIIVVVNITITIVVITKI------LRPSIGdkpcKQEKSSLFQISkSIGVLTpLLGLTWGFGLTtVFPGTNL 1285
Cdd:cd15438   148 LWSFLGPVCLIILVNAIIFVITVWKLaekfssINPDME----KLRKIRALTIT-AIAQLC-ILGCTWIFGFF-QFSDSTL 220
                         250       260       270
                  ....*....|....*....|....*....|
gi 530381549 1286 VFHIIFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd15438   221 VMSYLFTILNSLQGLFIFLLHCLLSKQVRE 250
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
1058-1317 7.16e-26

brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediates direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320654 [Multi-domain]  Cd Length: 291  Bit Score: 109.27  E-value: 7.16e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1058 VGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLvantwfIVVAAIQdnryILCKTACVAATFFIHFFY 1137
Cdd:cd15988    10 IGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNIL------ILVGQSQ----TLSKGVCTMTAAFLHFFF 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1138 LSVFFWMLTLGLMLFyrLVFILHETSRSTQKAIaFCLGYGCPLAISVITLGATQPREvYTRKNVCWLNWEDtKALLAFAI 1217
Cdd:cd15988    80 LSSFCWVLTEAWQSY--LAVIGRMRTRLVRKRF-LCLGWGLPALVVAVSVGFTRTKG-YGTASYCWLSLEG-GLLYAFVG 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1218 PALIIVVVNITITIVVITKIL-RPSIGDKPCKQE-------KSSLFQISKSIGVLT-----------------------P 1266
Cdd:cd15988   155 PAAVIVLVNMLIGIIVFNKLMsRDGISDKSKKQRagseaepCSSLLLKCSKCGVVSsaamssatassamaslwsscvvlP 234
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530381549 1267 LLGLTWGFGLTTVFPGTNLVFHIIFAILNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15988   235 LLALTWMSAVLAMTDRRSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVV 285
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
1050-1315 1.69e-25

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


Pssm-ID: 320673 [Multi-domain]  Cd Length: 258  Bit Score: 107.31  E-value: 1.69e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVvaAIQDNRYilcKTACVAA 1129
Cdd:cd16007     2 LLLSVITWVGIVISLVCLAICISTFCFL-RGLQTDRNTIHKNLCI-----NLFLAELLFLI--GIDKTQY---QIACPIF 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILhETSRSTQKAIAFClGYGCPLAisVITLGATQPREVYTRKNVCWLNwEDT 1209
Cdd:cd16007    71 AGLLHFFFLAAFSWLCLEGVQLYLMLVEVF-ESEYSRKKYYYLC-GYCFPAL--VVGISAAIDYRSYGTEKACWLR-VDN 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 KALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPckqEKSSLFQI-SKSIGVLTPL--LGLTWGFGLTTVFPGTnLV 1286
Cdd:cd16007   146 YFIWSFIGPVSFVIVVNLVFLMVTLHKMIRSSSVLKP---DSSRLDNIkSWALGAITLLflLGLTWAFGLLFINKES-VV 221
                         250       260
                  ....*....|....*....|....*....
gi 530381549 1287 FHIIFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd16007   222 MAYLFTTFNAFQGMFIFIFHCALQKKVHK 250
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
1052-1315 2.04e-25

epidermal growth factor-like module-containing mucin-like hormone receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4) and the leukocyte cell-surface antigen CD97, are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying number of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of EMR2, alternative splicing results in four isoforms possessing either two (EGF1,2), three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320555 [Multi-domain]  Cd Length: 263  Bit Score: 107.04  E-value: 2.04e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVeAVVWKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVVAAIQDNRyILCktACVAAtf 1131
Cdd:cd15439     4 LTVITYVGLIISLLCLFLAILT-FLLCRSIRNTSTSLHLQLSL-----CLFLADLLFLVGIDRTDNK-VLC--SIIAG-- 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLFY---RLVFILHETSRSTQKAIAFCLGYGCPlAISVITLGATQPrEVYTRKNVCWLNWEd 1208
Cdd:cd15439    73 FLHYLFLACFAWMFLEAVHLFLtvrNLKVVNYFSSHRFKKRFMYPVGYGLP-AVIVAISAAVNP-QGYGTPKHCWLSME- 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1209 TKALLAFAIPALIIVVVNITItIVVITKILRPSIG--DKPCKQEKSSLFQISKSIGVLTpLLGLTWGFGLTTVFPGTnLV 1286
Cdd:cd15439   150 KGFIWSFLGPVCVIIVINLVL-FCLTLWILREKLSslNAEVSTLKNTRLLTFKAIAQLF-ILGCTWILGLFQVGPVA-TV 226
                         250       260
                  ....*....|....*....|....*....
gi 530381549 1287 FHIIFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd15439   227 MAYLFTITNSLQGVFIFLVHCLLNRQVRE 255
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
1050-1315 7.17e-23

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


Pssm-ID: 320672 [Multi-domain]  Cd Length: 258  Bit Score: 99.60  E-value: 7.17e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVeAVVWKSVTKNRTSYMRHTCIvniaaSLLVANtwFIVVAAIQDNRYilcKTACVAA 1129
Cdd:cd16006     2 LLLTVITWVGIVISLVCLAICIFT-FCFFRGLQSDRNTIHKNLCI-----NLFIAE--FIFLIGIDKTEY---KIACPIF 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILHetSRSTQKAIAFCLGYGCPLAisVITLGATQPREVYTRKNVCWLNwEDT 1209
Cdd:cd16006    71 AGLLHFFFLAAFAWMCLEGVQLYLMLVEVFE--SEYSRKKYYYVAGYLFPAT--VVGVSAAIDYKSYGTEKACWLR-VDN 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 KALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTnLVFHI 1289
Cdd:cd16006   146 YFIWSFIGPVTFIILLNLIFLVITLCKMVKHSNTLKPDSSRLENIKSWVLGAFALLCLLGLTWSFGLLFINEET-IVMAY 224
                         250       260
                  ....*....|....*....|....*.
gi 530381549 1290 IFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd16006   225 LFTIFNAFQGMFIFIFHCALQKKVRK 250
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
1051-1308 1.54e-22

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: 98.96  E-value: 1.54e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1051 LLDIISYVGVGFSILslaaCLVVEAVVWKSVTKNRTSYMRHTCIvNIAASLLVANTWFIVVAAIQD-NRYILCKTACVaa 1129
Cdd:cd15997     3 ILTLITYLGCGISSI----FLGITLVTYLAFEKLRRDYPSKILI-NLCTALLMLNLVFLLNSWLSSfNNYGLCITVAA-- 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 tfFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTqkAIAFCL-GYGCPLAISVITL-------GATQPREVY-TRKN 1200
Cdd:cd15997    76 --FLHYFLLASFTWMGLEAVHMYFALVKVFNIYIPNY--ILKFCIaGWGIPAVVVALVLainkdfyGNELSSDSLhPSTP 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1201 VCWLNwEDTKALLAFAIPALIIVVVNITITIVVITKIlRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVF 1280
Cdd:cd15997   152 FCWIQ-DDVVFYISVVAYFCLIFLCNISMFITVLIQI-RSMKAKKPSRNWKQGFLHDLKSVASLTFLLGLTWGFAFFAWG 229
                         250       260
                  ....*....|....*....|....*...
gi 530381549 1281 PGtNLVFHIIFAILNVFQGLFILLFGCL 1308
Cdd:cd15997   230 PV-RIFFLYLFSICNTLQGFFIFVFHCL 256
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
1050-1315 2.56e-22

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


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 98.09  E-value: 2.56e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVeAVVWKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVVAAIQDNryilcKTACVAA 1129
Cdd:cd16005     2 LLLDVITWVGILLSLVCLLICIFT-FCFFRGLQSDRNTIHKNLCI-----SLFVAELLFLIGINRTDQ-----PIACAVF 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILHetSRSTQKAIAFCLGYGCPLAIsvITLGATQPREVYTRKNVCWLNWeDT 1209
Cdd:cd16005    71 AALLHFFFLAAFTWMFLEGVQLYIMLVEVFE--SEHSRRKYFYLVGYGMPALI--VAVSAAVDYRSYGTDKVCWLRL-DT 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 KALLAFAIPALIIVVVNITITIVVI------TKILRPSIGdkpCKQEKSSLfqISKSIGVLTpLLGLTWGFGLTTVFPGT 1283
Cdd:cd16005   146 YFIWSFIGPATLIIMLNVIFLGIALykmfhhTAILKPESG---CLDNIKSW--VIGAIALLC-LLGLTWAFGLMYINEST 219
                         250       260       270
                  ....*....|....*....|....*....|..
gi 530381549 1284 nLVFHIIFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd16005   220 -VIMAYLFTIFNSLQGMFIFIFHCVLQKKVRK 250
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
1058-1317 3.33e-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: 98.14  E-value: 3.33e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1058 VGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLvantwfIVVAAIQDNRYILCktACVAAtfFIHFFY 1137
Cdd:cd15990    13 VGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNAL------ILIGQTQTRNKVVC--TLVAA--FLHFFF 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1138 LSVFFWMLTLGLMLFyrLVFILHETSRSTQKAIaFCLGYGCPLAISVITLGATQPREvYTRKNVCWLNWEDtKALLAFAI 1217
Cdd:cd15990    83 LSSFCWVLTEAWQSY--MAVTGRLRNRIIRKRF-LCLGWGLPALVVAISVGFTKAKG-YGTVNYCWLSLEG-GLLYAFVG 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1218 PALIIVVVNITITIVVITKIL-RPSIGDKPCKQEK-SSLFqiskSIGVLTPLLGLTWGFGLTTVFPGTNLVFHIIFAILN 1295
Cdd:cd15990   158 PAAAVVLVNMVIGILVFNKLVsKDGITDKKLKERAgASLW----SSCVVLPLLALTWMSAVLAITDRRSALFQILFAVFD 233
                         250       260
                  ....*....|....*....|..
gi 530381549 1296 VFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15990   234 SLEGFVIVMVHCILRREVQDAV 255
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
1052-1315 4.03e-22

EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the leukocyte cell-surface antigen CD97 and the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4), are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily B2 of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying numbers of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of CD97, alternative splicing results in three isoforms possessing either three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. On the other hand, EMR2 generates four isoforms possessing either two (EGF1,2), three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. For example, CD97, which is involved in angiogenesis and the migration and invasion of tumor cells, has been shown to promote cell aggregation in a GPS proteolysis-dependent manner. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320597 [Multi-domain]  Cd Length: 262  Bit Score: 97.59  E-value: 4.03e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVVAAIQDNryilcKTACVAATF 1131
Cdd:cd15931     4 LEWINRVGVIVSLFCLGLAIFTFLLC-RWIPKINTTAHLHLCL-----CLSMSHTLFLAGIEYVEN-----ELACTVMAG 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLFY--RLVFILHETSRSTQKAIAFCL-GYGCPLAISVITlGATQPREvYTRKNVCWLNWEd 1208
Cdd:cd15931    73 LLHYLFLASFVWMLLEALQLHLlvRRLTKVQVIQRDGLPRPLLCLiGYGVPFLIVGVS-ALVYSDG-YGEAKMCWLSQE- 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1209 TKALLAFAIPALIIVVVNiTITIVVITKILRPSIGD--KPCKQEKSSLFQISKSIGVLTpLLGLTWGFGLTTVFPgTNLV 1286
Cdd:cd15931   150 RGFNWSFLGPVIAIIGIN-WILFCATLWCLRQTLSNmnSDISQLKDTRLLTFKAVAQLF-ILGCTWVLGLFQTNP-VALV 226
                         250       260
                  ....*....|....*....|....*....
gi 530381549 1287 FHIIFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd15931   227 FQYLFTILNSLQGAFLFLVHCLLNKEVRE 255
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
1051-1317 4.93e-22

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


Pssm-ID: 320383 [Multi-domain]  Cd Length: 263  Bit Score: 97.23  E-value: 4.93e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1051 LLDIISYVGVGFSILSLAACLVVEAVVwkSVTKNRtsymRHTCIVNIAASLLVANTWFIVVAAIQDNryilcKTACVAAT 1130
Cdd:cd15255     3 TLRTLSFIGCGVSLCALIVTFILFLAV--GVPKSE----RTTVHKNLIFALAAAEFLLMFSEWAKGN-----QVACWAVT 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1131 FFIHFFYLSVFFWMLTLGLMLFYRLVFI-LHETSRSTqkaIAFCLGYGCPLAISVITLGATQPRevYTRKNVCWLNWEdT 1209
Cdd:cd15255    72 ALLHLFFLAAFSWMLVEGLLLWSKVVAVnMSEDRRMK---FYYVTGWGLPVVIVAVTLATSFNK--YVADQHCWLNVQ-T 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 KALLAFAIPALIIVVVN--ITITIVVIT--------KILRPSIGDKpcKQEKSSLFQISKSIGVLTPLLGLTWgfgLTTV 1279
Cdd:cd15255   146 DIIWAFVGPVLFVLTVNtfVLFRVVMVTvssarrraKMLTPSSDLE--KQIGIQIWATAKPVLVLLPVLGLTW---LCGV 220
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 530381549 1280 FPGTNLVFHIIFAILNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15255   221 LVHLSDVWAYVFITLNSFQGLYIFLVYAIYNSEVRNAI 258
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
1052-1306 7.13e-22

orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR128 is an orphan receptor of the adhesion family (subclass B2) that belongs to the class B GPCRs. Expression of GPR128 was detected in the mouse intestinal mucosa and is thought to be involved in energy balance, as its knockout mice showed a decrease in body weight gain and an increase in intestinal contraction frequency compared to wild-type controls. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320385 [Multi-domain]  Cd Length: 303  Bit Score: 98.02  E-value: 7.13e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEaVVWKSVTKNRTSYMrhtcIVNIAASLLVANTWFIVVAAIQDNRYILCKTA------ 1125
Cdd:cd15257     4 LDIISTIGCVLSIAGLVITIIFH-LHTRKLRKSSVTWV----LLNLCSSLLLFNIIFTSGVENTNNDYEISTVPdretnt 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1126 --------------CVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFcLGYGCPLAISVITLGAT- 1190
Cdd:cd15257    79 vllseeyvepdtdvCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQASA-IGWGIPAVVVAITLGATy 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1191 -------QPREVYTRKNVCWL-----NWEDTKALL-AFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQeKSSLFQI 1257
Cdd:cd15257   158 rfptslpVFTRTYRQEEFCWLaaldkNFDIKKPLLwGFLLPVGLILITNVILFIMTSQKVLKKNNKKLTTKK-RSYMKKI 236
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530381549 1258 SKSIGVLTpLLGLTWGFG--LTTVFPGTNLVFHIIFAILNVFQGLFI-LLFG 1306
Cdd:cd15257   237 YITVSVAV-VFGITWILGylMLVNNDLSKLVFSYIFCITNTTQGVQIfILYT 287
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
1051-1315 1.31e-21

Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; member of the class B2 family of seven-transmembrane G protein-coupled receptors; ETL (EGF-TM7-latrophilin-related protein) belongs to Group I adhesion GPCRs, which also include latrophilins (also called lectomedins or latrotoxin receptors). All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. ETL, for instance, contains EGF-like repeats, which also present in other EGF-TM7 adhesion GPCRs, such as Cadherin EGF LAG seven-pass G-type receptors (CELSR1-3), EGF-like module receptors (EMR1-3), CD97, and Flamingo. ETL is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320553 [Multi-domain]  Cd Length: 258  Bit Score: 96.10  E-value: 1.31e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1051 LLDIISYVGVGFSILSLAAClVVEAVVWKSVTKNRTSYMRHTCivniaASLLVANTWFIVVAAIQDNRYIlcktaCVAAT 1130
Cdd:cd15437     3 VLTRITQLGIIISLICLSMC-IFTFWFFSEIQSTRTTIHKNLC-----CSLFLAELIFLIGINMNANKLF-----CSIIA 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1131 FFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFclGYGCPLAisVITLGATQPREVYTRKNVCWLNWEDTk 1210
Cdd:cd15437    72 GLLHYFFLAAFAWMCIEGIHLYLIVVGVIYNKGFLHKNFYIF--GYGSPAV--VVGISAALGYKYYGTTKVCWLSTENN- 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1211 ALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTNLVFHIi 1290
Cdd:cd15437   147 FIWSFIGPACLIILVNLLAFGVIIYKVFRHTAMLKPEVSCYENIRSCARGALALLFLLGATWIFGVLHVVYGSVVTAYL- 225
                         250       260
                  ....*....|....*....|....*
gi 530381549 1291 FAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd15437   226 FTISNAFQGMFIFIFLCVLSRKIQE 250
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
1052-1322 5.50e-21

Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320657 [Multi-domain]  Cd Length: 254  Bit Score: 94.14  E-value: 5.50e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRtsymrHTCIVNIAASLLVANTWFIVVAAIQDNRYIlcktaCVAATF 1131
Cdd:cd15991     4 LKIITYTTVSLSLVALLITFILLVLI-RTLRSNL-----HSIHKNLVAALFFSELIFLIGINQTENPFV-----CTVVAI 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLfYRLvfiLHETSRSTQKAIAF--CLGYGCPLAISVITLGATQprEVYTRKNVCWLNWEDT 1209
Cdd:cd15991    73 LLHYFYMSTFAWMFVEGLHI-YRM---LTEVRNINTGHMRFyyVVGWGIPAIITGLAVGLDP--QGYGNPDFCWLSVQDT 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 kALLAFAIPALIIVVVNITITIVVItkilRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGTnLVFHI 1289
Cdd:cd15991   147 -LIWSFAGPIGIVVIINTVIFVLAA----KASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGLMAVNSDT-LSFHY 220
                         250       260       270
                  ....*....|....*....|....*....|...
gi 530381549 1290 IFAILNVFQGLFILLFGCLWDLKVQEALLNKFS 1322
Cdd:cd15991   221 LFAIFSCLQGIFIFFFHCIFNKEVRKHLKNVLT 253
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
1050-1307 3.39e-20

orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B secretin-like receptors of seven-transmembrane G protein-coupled receptors; GPR64 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR97, GPR112, GPR114, and GPR126. GPR64 is mainly expressed in the epididymis of male reproductive tract, and targeted deletion of GPR64 causes sperm stasis and efferent duct blockage due to abnormal fluid reabsorption, resulting in male infertility. GPR64 is also over-expressed in Ewing's sarcoma (ES), as well as upregulated in other carcinomas from kidney, prostate or lung, and promotes invasiveness and metastasis in ES via the upregulation of placental growth factor (PGF) and matrix metalloproteinase (MMP) 1. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 92.20  E-value: 3.39e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVeAVVWKSVTKNRTSYMrhtcIVNIAASLLVANTWFIVVAAIQdnRYILCKTACVAA 1129
Cdd:cd15444     2 LILTFITYIGCGLSAIFLSVTLVT-YIAFEKIRRDYPSKI----LIQLCVALLLLNLVFLLDSWIA--LYKDIVGLCISV 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRstQKAIAFCL-GYGCPLAISVITLGATQPREVYTRK--------- 1199
Cdd:cd15444    75 AVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIR--KYILKFCIvGWGVPAVVVAIVLAVSKDNYGLGSYgkspngstd 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1200 NVCWLNWEdtkalLAFAIPAL----IIVVVNITITIVVITKILRPSIGDKPCKQEKSSLfQISKSIGVLTPLLGLTWGFG 1275
Cdd:cd15444   153 DFCWINNN-----IVFYITVVgyfcVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSL-QDLRSVAGITFLLGITWGFA 226
                         250       260       270
                  ....*....|....*....|....*....|..
gi 530381549 1276 LTTVFPGtNLVFHIIFAILNVFQGLFILLFGC 1307
Cdd:cd15444   227 FFAWGPV-NLAFMYLFAIFNTLQGFFIFIFYC 257
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
1058-1317 1.01e-19

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


Pssm-ID: 320655 [Multi-domain]  Cd Length: 293  Bit Score: 91.28  E-value: 1.01e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1058 VGVGFSILSLAACLVVEAVVWKSVTKNRTSYMRHTCIVNIAASLLvantwfIVVAAIQDNRyilcKTACVAATFFIHFFY 1137
Cdd:cd15989    12 VGCGLSCLALITLAVVYAALWRYIRSERSIILINFCLSIISSNIL------ILVGQTQTHN----KGICTMTTAFLHFFF 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1138 LSVFFWMLTLGLMLFYRLVFILHetSRSTQKAIaFCLGYGCPLAISVITLGATQPREvYTRKNVCWLNWEDtKALLAFAI 1217
Cdd:cd15989    82 LASFCWVLTEAWQSYMAVTGKIR--TRLIRKRF-LCLGWGLPALVVAISMGFTKAKG-YGTPHYCWLSLEG-GLLYAFVG 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1218 PALIIVVVNITITIVVITKIL-RPSIGDKPCKQEKSSLFQISKSIG------------------------------VLTP 1266
Cdd:cd15989   157 PAAAVVLVNMVIGILVFNKLVsRDGILDKKLKHRAGQMSEPHSGLTlkcakcgvvsttalsattasnamaslwsscVVLP 236
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530381549 1267 LLGLTWGFGLTTVFPGTNLVFHIIFAILNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15989   237 LLALTWMSAVLAMTDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAF 287
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
1050-1315 1.51e-19

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


Pssm-ID: 320552 [Multi-domain]  Cd Length: 258  Bit Score: 89.85  E-value: 1.51e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1050 ILLDIISYVGVGFSILSLAACLVVeAVVWKSVTKNRTSYMRHTCIvniaaSLLVANTWFIVvaAIQDNRYILcktACVAA 1129
Cdd:cd15436     2 LLLFVITWVGIVISLVCLLICIFT-FCFFRGLQTDRNTIHKNLCI-----NLFIAELLFLI--GINRTQYTI---ACPIF 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILhETSRSTQKAIAFClGYGCPlaISVITLGATQPREVYTRKNVCWLNwEDT 1209
Cdd:cd15436    71 AGLLHFFFLAAFCWLCLEGVQLYLLLVEVF-ESEYSRRKYFYLC-GYSFP--ALVVAVSAAIDYRSYGTEKACWLR-VDN 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1210 KALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPckqEKSSLFQI-SKSIGVLTPL--LGLTWGFGLTTVFPGTnLV 1286
Cdd:cd15436   146 YFIWSFIGPVTFVITLNLVFLVITLHKMVSHSDLLKP---DSSRLDNIkSWALGAIALLflLGLTWSFGLMFINEES-VV 221
                         250       260
                  ....*....|....*....|....*....
gi 530381549 1287 FHIIFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd15436   222 MAYLFTIFNAFQGVFIFIFHCALQKKVRK 250
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
1051-1315 4.52e-19

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: 88.79  E-value: 4.52e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1051 LLDIISYVGVGFSILSLAACLVVeavvWKSVTKNRTSYMRHTcIVNIAASLLVANTWFIVVAAIQDNRyilCKTACVAAT 1130
Cdd:cd15996     3 VLTFITYIGCGISAIFSAATLLT----YIAFEKLRRDYPSKI-LMNLSTALLFLNLVFLLDGWIASFE---IDELCITVA 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1131 FFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRstQKAIAFCL-GYGCPLAISVITLGATQPREVYTRK---------- 1199
Cdd:cd15996    75 VLLHFFLLATFTWMGLEAIHMYIALVKVFNTYIR--RYILKFCIiGWGLPALIVSIVLASTNDNYGYGYYgkdkdgqggd 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1200 NVCWLNwEDTKALLAFAIPALIIVVVNITITIVVITKILRPSiGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTV 1279
Cdd:cd15996   153 EFCWIK-NPVVFYVTCAAYFGIMFLMNVAMFIVVMVQICGRN-GKRSNRTLREEILRNLRSVVSLTFLLGMTWGFAFFAW 230
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 530381549 1280 FPgTNLVFHIIFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd15996   231 GP-VNLAFMYLFTIFNSLQGLFIFVFHCALKENVQK 265
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
1052-1315 6.53e-19

orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Group VIII adhesion GPCRs include orphan GPCRs such as GPR56, GPR64, GPR97, GPR112, GPR114, and GPR126. GPR56 is involved in the regulation of oligodendrocyte development and myelination in the central nervous system via coupling to G(12/13) proteins, which leads to the activation of RhoA GTPase. GPR126, on the other hand, is required for Schwann cells, but not oligodendrocyte myelination in the peripheral nervous system. Gpr64 is mainly expressed in the epididymis of male reproductive tract, and targeted deletion of GPR64 causes sperm stasis and efferent duct blockage due to abnormal fluid reabsorption, resulting in male infertility. GPR64 is also over-expressed in Ewing's sarcoma (ES), as well as upregulated in other carcinomas from kidney, prostate or lung, and promotes invasiveness and metastasis in ES via the upregulation of placental growth factor (PGF) and matrix metalloproteinase (MMP) 1. GPR97 is identified as a lymphatic adhesion receptor that is specifically expressed in lymphatic endothelium, but not in blood vascular endothelium, and is shown to regulate migration of lymphatic endothelial cells via the small GTPases RhoA and cdc42. GPR112 is specifically expressed in normal enterochromatin cells and gastrointestinal neuroendocrine carcinoma cells, but its biological function is unknown. GPR114 is mainly found in granulocytes (polymorphonuclear leukocytes), and GPR114-transfected cells induced an increase in cAMP levels via coupling to G(s) protein. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320386 [Multi-domain]  Cd Length: 267  Bit Score: 88.24  E-value: 6.53e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVWKSvtknRTSYMRHTcIVNIAASLLVANTWFIVVAAIQDNRyilCKTACVAATF 1131
Cdd:cd15258     4 LTFISYVGCGISAIFLAITILTYIAFRKL----RRDYPSKI-HMNLCAALLLLNLAFLLSSWIASFG---SDGLCIAVAV 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRstQKAIAFCL-GYGCPlAISVITLGATQP----------REVYTRKN 1200
Cdd:cd15258    76 ALHYFLLACLTWMGLEAFHLYLLLVKVFNTYIR--RYILKLCLvGWGLP-ALLVTLVLSVRSdnygpitipnGEGFQNDS 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1201 VCWLnwedtKALLAFAIPAL----IIVVVNITITIVVITKILRpsIGDKPCKQEKSSLFQISKSIGVLTPLLGLTWGFGL 1276
Cdd:cd15258   153 FCWI-----RDPVVFYITVVgyfgLTFLFNMVMLATVLVQICR--LREKAQATPRKRALHDLLTLLGLTFLLGLTWGLAF 225
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 530381549 1277 TTvFPGTNLVFHIIFAILNVFQGLFILLFGCLWDLKVQE 1315
Cdd:cd15258   226 FA-WGPFNLPFLYLFAIFNSLQGFFIFIWYCSMKENVRK 263
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
1052-1322 7.47e-17

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


Pssm-ID: 341321 [Multi-domain]  Cd Length: 273  Bit Score: 82.27  E-value: 7.47e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVveAVV----WKSVTKNRTSYMRHTCIvniaASLLVANTWFIVVAAIQDNRYILCKT--- 1124
Cdd:cd15041     1 LLVVYYIYLVGYSLSLVALLP--AIViflyFRSLRCTRIRLHINLFL----SFILRAVFWIIWDLLVVYDRLTSSGVetv 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1125 ------ACVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQkaIAFCLGYGCPLAISVITLGAtqpREVYTR 1198
Cdd:cd15041    75 lmqnpvGCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSSLK--LYYAIGWGLPLVIVVIWAIV---RALLSN 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1199 KNvCWLNWEDTKALLAFAIPALIIVVVN----ITITIVVITKiLRPSIGDKPCKQEKSSlfqisKSIGVLTPLLGLTwgF 1274
Cdd:cd15041   150 ES-CWISYNNGHYEWILYGPNLLALLVNlfflINILRILLTK-LRSHPNAEPSNYRKAV-----KATLILIPLFGIQ--Y 220
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530381549 1275 GLTTVFPGT----NLVFHIIFAILNVFQGLFILLFGCLWDLKVQEALLNKFS 1322
Cdd:cd15041   221 LLTIYRPPDgsegELVYEYFNAILNSSQGFFVAVIYCFLNGEVQSELKRKWS 272
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
1051-1316 3.40e-16

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


Pssm-ID: 320659 [Multi-domain]  Cd Length: 254  Bit Score: 79.89  E-value: 3.40e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1051 LLDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYmrHTcivNIAASLLVANTWFIVVAAIQDNRYIlcktaCVAAT 1130
Cdd:cd15993     3 TLAIVTYSSVSASLAALVLTFSVLTCL-RGLKSNTRGI--HS---NIAAALFLSELLFLLGINRTENQFL-----CTVVA 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1131 FFIHFFYLSVFFWMLTLGLMLfYRLVFILHETSRSTQKaIAFCLGYGCPLAISVITLGATQprEVYTRKNVCWLNWEDtK 1210
Cdd:cd15993    72 ILLHYFFLSTFAWLFVQGLHI-YRMQTEARNVNFGAMR-FYYAIGWGVPAIITGLAVGLDP--EGYGNPDFCWISIHD-K 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1211 ALLAFAIPALIIVVVNITITIVVITKILRPsiGDKPCKqeKSSLFQISKSIGVLTPLLGLTWGFGLTTVfPGTNLVFHII 1290
Cdd:cd15993   147 LVWSFAGPIVVVIVMNGVMFLLVARMSCSP--GQKETK--KTSVLMTLRSSFLLLLLISATWLFGLLAV-NNSVLAFHYL 221
                         250       260
                  ....*....|....*....|....*.
gi 530381549 1291 FAILNVFQGLFILLFGCLWDLKVQEA 1316
Cdd:cd15993   222 HAILCCLQGLAVLLLFCVLNEEVQEA 247
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
993-1036 6.14e-15

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


Pssm-ID: 460350  Cd Length: 44  Bit Score: 70.03  E-value: 6.14e-15
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 530381549   993 KCVFWNFrLANNTGGWDSSGCYVEEGDGDNVTCICDHLTSFSIL 1036
Cdd:pfam01825    2 QCVFWDF-TNSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
990-1042 2.44e-14

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: 68.18  E-value: 2.44e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 530381549    990 GETKCVFWNFRlannTGGWDSSGCYVEEGDGDNVTCICDHLTSFSILMSPDSP 1042
Cdd:smart00303    1 FNPICVFWDES----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPPI 49
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
1089-1322 7.04e-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 [Multi-domain]  Cd Length: 272  Bit Score: 73.56  E-value: 7.04e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1089 MRHTCIVNIAASLLVANTWFIVVAAIQDNRYILCKTACVAATFFiHFFYLSVFFWMLTLGLMLFYRLVfilhET-SRSTQ 1167
Cdd:cd15263    35 LRNTIHTNLMFTYILADLTWILTLTLQVSIGEDQKSCIILVVLL-HYFHLTNFFWMFVEGLYLYMLVV----ETfSGENI 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1168 KAIAF-CLGYGCPLAISVI---------TLGATQPREVYTRKNVCWLNWEDTKALlaFAIPALIIVVVNIT----ITIVV 1233
Cdd:cd15263   110 KLRVYaFIGWGIPAVVIVIwaivkalapTAPNTALDPNGLLKHCPWMAEHIVDWI--FQGPAILVLAVNLVflvrIMWVL 187
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1234 ITKiLRPSigdkpCKQEKSSLFQISKSIGVLTPLLGLTWGFGLTTVFPGT-NLVFHIIFAILNVFQGLFILLFGCLWDLK 1312
Cdd:cd15263   188 ITK-LRSA-----NTVETQQYRKAAKALLVLIPLLGITYILVIAGPTEGIaANIFEYVRAVLLSTQGFTVALFYCFLNTE 261
                         250
                  ....*....|
gi 530381549 1313 VQEALLNKFS 1322
Cdd:cd15263   262 VRNTLRHHFE 271
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
1054-1322 4.29e-13

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


Pssm-ID: 320392 [Multi-domain]  Cd Length: 265  Bit Score: 70.91  E-value: 4.29e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1054 IISYVGVGFSILSLAACLVVEAVvWKSVTKNRTSYMRHTcivnIAASLLVANTWFIVVAAI-----QDNRYiLCKTacVA 1128
Cdd:cd15264     6 IIYYLGFSISLVALAVALIIFLY-FRSLRCLRNNIHCNL----IVTFILRNVTWFIMQNTLteihhQSNQW-VCRL--IV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1129 ATFfiHFFYLSVFFWMLTLGLMLFYRLVFilhetSRSTQKA---IAFCLGYGCPLAISVITlgATQPreVYTRKNVCWLN 1205
Cdd:cd15264    78 TVY--NYFQVTNFFWMFVEGLYLHTMIVW-----AYSADKIrfwYYIVIGWCIPCPFVLAW--AIVK--LLYENEHCWLP 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1206 -WEDTKALLAFAIPALIIVVVNI----TITIVVITKiLRPSigdkpCKQEKSSLFQISKSIGVLTPLLGLTwgFGLTTVF 1280
Cdd:cd15264   147 kSENSYYDYIYQGPILLVLLINFiflfNIVWVLITK-LRAS-----NTLETIQYRKAVKATLVLLPLLGIT--YMLFFIN 218
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 530381549 1281 PGTNLVFHIIF----AILNVFQGLFILLFGCLWDLKVQEALLNKFS 1322
Cdd:cd15264   219 PGDDKTSRLVFiyfnTFLQSFQGLFVAVFYCFLNGEVRSAIRKKFS 264
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
1052-1304 3.97e-12

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: 67.92  E-value: 3.97e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVwKSVTKNRTSYMRhtcivNIAASLLVANTWFIVVAAIQDNRYilcktACVAATF 1131
Cdd:cd15992     4 LKTLTWSSVGVTLGFLLLTFLFLLCL-RALRSNKTSIRK-----NGATALFLSELVFILGINQADNPF-----ACTVIAI 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYLSVFFWMLTLGLMLfYRLVFILHETSRSTQKaIAFCLGYGCPLAISVITLGATQprEVYTRKNVCWLNWEDTkA 1211
Cdd:cd15992    73 LLHFFYLCTFSWLFLEGLHI-YRMLSEVRDINYGPMR-FYYLIGWGVPAFITGLAVGLDP--EGYGNPDFCWLSIYDT-L 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1212 LLAFAIPalIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTpLLGLTWGFGLTTVFPGTnLVFHIIF 1291
Cdd:cd15992   148 IWSFAGP--VAFAVSMNVFLYILSSRASCSAQQQSFEKKKGPVSGLRTAFTVLL-LVSVTCLLALLSVNSDV-ILFHYLF 223
                         250
                  ....*....|...
gi 530381549 1292 AILNVFQGLFILL 1304
Cdd:cd15992   224 AGFNCLQGPFIFL 236
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
1051-1308 4.93e-12

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


Pssm-ID: 320387 [Multi-domain]  Cd Length: 260  Bit Score: 67.79  E-value: 4.93e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1051 LLDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTsyMRHTcIVNIAASLLVANTWFivVAAIQDNRYILcktACVAAT 1130
Cdd:cd15259     3 LLHPVVYAGAALCLLCLLATIITYIVFHRLIRISRK--GRHM-LVNLCLHLLLTCVVF--VGGINRTANQL---VCQAVG 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1131 FFIHFFYLSVFFWMlTLGLMLFYRLVfilHETSRSTQKA----------IAFCL-GYGCPLAISVITlGATQPREvYTRK 1199
Cdd:cd15259    75 ILLHYSTLCTLLWV-GVTARNMYKQV---TKTAKPPQDEdqpprppkpmLRFYLiGWGIPLIICGIT-AAVNLDN-YSTY 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1200 NVCWLNWEDTkaLLAFAIPALIIVVVNItITIVVITKILRpsigdkpcKQEKSSLFQISKSIGVLTpLLGLTWGFGLTTV 1279
Cdd:cd15259   149 DYCWLAWDPS--LGAFYGPAALIVLVNC-IYFLRIYCQLK--------GAPVSFQSQLRGAVITLF-LYVAMWACGALAV 216
                         250       260       270
                  ....*....|....*....|....*....|..
gi 530381549 1280 ---FPGtNLVFHIIFAILNVFQGLFILLFGCL 1308
Cdd:cd15259   217 sqrYFL-DLVFSCLYGATCSSLGLFVLIHHCL 247
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
1054-1317 8.14e-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 [Multi-domain]  Cd Length: 265  Bit Score: 64.19  E-value: 8.14e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1054 IISYVGVGFSILSLaaclVVEAVVWKSVTKNRTsyMRHTCIVNIAASLLVAN-TWFIVVAAIQDNRYILCKTACVAATFF 1132
Cdd:cd15445     6 IINYLGHCISLVAL----LVAFVLFLRLRSIRC--LRNIIHWNLITAFILRNaTWFVVQLTMSPEVHQSNVVWCRLVTAA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1133 IHFFYLSVFFWMLTLGLMLFYRLVfiLHETSRSTQKAIAFCLGYGCPLAISVitlgATQPREVYTRKNVCWLNWE-DTKA 1211
Cdd:cd15445    80 YNYFHVTNFFWMFGEGCYLHTAIV--LTYSTDKLRKWMFICIGWCIPFPIIV----AWAIGKLYYDNEKCWFGKRaGVYT 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1212 LLAFAIPALIIVVVNI----TITIVVITKiLRPSIGDKPCKQEKSSlfqisKSIGVLTPLLGLTwgFGLTTVFPGTNLVF 1287
Cdd:cd15445   154 DYIYQGPMILVLLINFiflfNIVRILMTK-LRASTTSETIQYRKAV-----KATLVLLPLLGIT--YMLFFVNPGEDEIS 225
                         250       260       270
                  ....*....|....*....|....*....|....
gi 530381549 1288 HIIF----AILNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15445   226 RIVFiyfnSFLESFQGFFVSVFYCFLNSEVRSAV 259
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
1110-1322 8.11e-09

pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PACAP-R1) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and vasoactive intestinal peptide (VIP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. PACAP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level.


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 58.44  E-value: 8.11e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1110 VVAAIQDNRYILCKT-ACVAATFFIHFFYLSVFFWMLTLGLMLFYRLVfilhETSRSTQKAIAF--CLGYGCPLAisVIT 1186
Cdd:cd15987    60 VLYAEQDSDHCFVSTvECKAVMVFFHYCVMSNYFWLFIEGLYLFTLLV----ETFFPERRYFYWytIIGWGTPTI--CVT 133
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1187 LGATQprEVYTRKNVCWLNWEDTKALLAFAIPALIIVVVN----ITITIVVITKILRPSIGDkpckQEKSSLFQISKSIG 1262
Cdd:cd15987   134 VWAVL--RLHFDDTGCWDMNDNTALWWVIKGPVVGSIMINfvlfIGIIIILVQKLQSPDIGG----NESSIYLRLARSTL 207
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530381549 1263 VLTPLLGL---TWGFGLTTVFPGTNLVFHIifaILNVFQGLFILLFGCLWDLKVQEALLNKFS 1322
Cdd:cd15987   208 LLIPLFGIhytVFAFSPENVSKRERLVFEL---GLGSFQGFVVAVLYCFLNGEVQSEIKRKWR 267
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
1126-1322 2.03e-08

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


Pssm-ID: 320388 [Multi-domain]  Cd Length: 267  Bit Score: 56.90  E-value: 2.03e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1126 CVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFIlhetSRSTQKAIAFCL--GYGCPLAISVITLGAtqpREVYTRKN-VC 1202
Cdd:cd15260    75 CQALHVLLQYFMVCNYFWMFCEGLYLHTVLVVA----FISEKSLMRWFIaiGWGVPLVITAIYAGV---RASLPDDTeRC 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1203 WLnwEDTKALLAFAIPALIIVVVN----ITITIVVITKiLRPSigdkPCKQEKSSLFQISKSIGVLTPLLGLTwgFGLTT 1278
Cdd:cd15260   148 WM--EESSYQWILIVPVVLSLLINliflINIVRVLLTK-LRAT----SPNPAPAGLRKAVRATLILIPLLGLQ--FLLIP 218
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 530381549 1279 VFPGTN----LVFHIIFAILNVFQGLFILLFGCLWDLKVQEALLNKFS 1322
Cdd:cd15260   219 FRPEPGapleTIYQYVSALLTSLQGLCVAVLFCFCNGEVIAAIKRKWR 266
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
1095-1309 2.62e-08

orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR97 is an orphan receptor that has been classified into the group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR112, GPR114, and GPR126. GPR97 is identified as a lymphatic adhesion receptor that is specifically expressed in lymphatic endothelium, but not in blood vascular endothelium, and is shown to regulate migration of lymphatic endothelial cells via the small GTPases RhoA and cdc42. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320558 [Multi-domain]  Cd Length: 277  Bit Score: 56.73  E-value: 2.62e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1095 VNIAASLLVANTWFIVVAAIQDNRYilcKTACVAATFFIHFFYLSVFFWMLTLGLMLFyrLVFILHETSRSTQKAIAFCL 1174
Cdd:cd15442    46 VNLSSSLLLLNLAFLLNSGVSSRAH---PGLCKALGGVTHYFLLCCFTWMAIEAFHLY--LLAIKVFNTYIHHYFAKLCL 120
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1175 -GYGCPlAISVITLGATQPREVYT-----RKNVCWLNWEDTKALLAFAIPA----LIIVVVNITITIVVITKIL---RPS 1241
Cdd:cd15442   121 vGWGFP-ALVVTITGSINSYGAYTimdmaNRTTLHLCWINSKHLTVHYITVcgyfGLTFLFNTVVLGLVAWKIFhlqSAT 199
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530381549 1242 IGDKPCKQEKSSLFQISksigvLTPLLGLTWGFGLTTvfPGTNLVFHI-IFAILNVFQGLFIllfgCLW 1309
Cdd:cd15442   200 AGKEKCQAWKGGLTVLG-----LSCLLGVTWGLAFFT--YGSMSVPTVyIFALLNSLQGLFI----FIW 257
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
1054-1321 8.74e-08

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


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 54.97  E-value: 8.74e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1054 IISYVGVGFSILSLAACLVVeAVVWKSVtknrtSYMRHTCIVNIAASLLVANTWFIVVAAIQDNRYILCKTACVAATFFI 1133
Cdd:cd15446     6 IINYLGHCISVGALVVAFLL-FLCLRSI-----RCLRNIIHWNLITTFILRNVMWFLLQMIDHNIHESNEVWCRCITTIY 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1134 HFFYLSVFFWMLTLGLMLFYRLVfiLHETSRSTQKAIAFCLGYGCPLAISVitlgATQPREVYTRKNVCWLNWEDTKAL- 1212
Cdd:cd15446    80 NYFVVTNFFWMFVEGCYLHTAIV--MTYSTDKLRKWVFLFIGWCIPCPIIV----AWAIGKLYYENEQCWFGKEPGKYId 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1213 LAFAIPALIIVVVNIT----ITIVVITKiLRPSIGDKPCKQEKSSlfqisKSIGVLTPLLGLTwgFGLTTVFPGTNLVFH 1288
Cdd:cd15446   154 YIYQGPVILVLLINFVflfnIVRILMTK-LRASTTSETIQYRKAV-----KATLVLLPLLGIT--YMLFFVNPGEDDISQ 225
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 530381549 1289 IIF----AILNVFQGLFILLFGCLWDLKVQEALLNKF 1321
Cdd:cd15446   226 IVFiyfnSFLQSFQGFFVSVFYCFLNGEVRSAARKRW 262
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
285-361 1.06e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.58  E-value: 1.06e-07
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530381549    285 EGDTVSLVCE-KEVLSSNVSWRYEEQQLeIQNSSRFSIytalfNNMTSVSKLTIHNITPGDAGEYVCKLILDIFEYEC 361
Cdd:smart00410    8 EGESVTLSCEaSGSPPPEVTWYKQGGKL-LAESGRFSV-----SRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
1124-1317 4.99e-07

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


Pssm-ID: 320399 [Multi-domain]  Cd Length: 267  Bit Score: 52.81  E-value: 4.99e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1124 TACVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILheTSRSTQKAIAFCLGYGCPLAISVITlgatqpreVYTRK---- 1199
Cdd:cd15271    75 VACKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTF--TSDRKYFWWYILIGWGAPSVTVTVW--------VLTRLqydn 144
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1200 NVCwlnWEDTKALLAFAI--PALIIVVVNITITIVVI----TKILRPSIGdkpcKQEKSSLFQISKSIGVLTPLLGLTwg 1273
Cdd:cd15271   145 RGC---WDDLESRIWWIIktPILLSVFVNFLIFINVIrilvQKLKSPDVG----GNDTSHYMRLAKSTLLLIPLFGVH-- 215
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 530381549 1274 FGLTTVFP-GTNLVFHIIFAI-LNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15271   216 YVVFAFFPeHVGVEARLYFELvLGSFQGFIVALLYCFLNGEVQAEI 261
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
1126-1321 5.89e-07

vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Vasoactive intestinal peptide (VIP) receptor 2 is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. VIP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320652 [Multi-domain]  Cd Length: 269  Bit Score: 52.50  E-value: 5.89e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1126 CVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTqkaIAFCLGYGCPlAISVITLGATQpreVYTRKNVCWLN 1205
Cdd:cd15986    79 CKVSLVILQYCIMANFYWLLVEGLYLHTLLVVIFSENRHFI---VYLLIGWGIP-TVFIIAWIVAR---IYLEDTGCWDT 151
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1206 WEDTKALLAFAIPALIIVVVN----ITITIVVITKILRPSIGDKPCKQEKsslfQISKSIGVLTPLLGLTwgFGLTTVFP 1281
Cdd:cd15986   152 NDHSVPWWVIRIPIIISIILNfilfISIIRILLQKLRSPDVGGNDQSQYK----RLAKSTLLLIPLFGVH--YIVFVYFP 225
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 530381549 1282 GTNLV-FHIIFAI-LNVFQGLFILLFGCLWDLKVQEALLNKF 1321
Cdd:cd15986   226 DSSSSnYQIFFELcLGSFQGLVVAILYCFLNSEVQGELKRKW 267
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
1124-1314 6.69e-07

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


Pssm-ID: 320596 [Multi-domain]  Cd Length: 268  Bit Score: 52.43  E-value: 6.69e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1124 TACVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAFclGYGCPlaisVITLGATQPREVYTRKNVCW 1203
Cdd:cd15930    75 VGCKASMVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLI--GWGAP----TVFVTVWIVARLYFEDTGCW 148
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1204 LNWEDTKALLAFAIPALIIVVVN----ITITIVVITKILRPSIGdkpcKQEKSSLFQISKSIGVLTPLLG---LTWGFGL 1276
Cdd:cd15930   149 DINDESPYWWIIKGPILISILVNfvlfINIIRILLQKLRSPDIG----GNESSQYKRLARSTLLLIPLFGihyIVFAFFP 224
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 530381549 1277 TTVFPGTNLVFHIifaILNVFQGLFILLFGCLWDLKVQ 1314
Cdd:cd15930   225 ENISLGIRLYFEL---CLGSFQGFVVAVLYCFLNGEVQ 259
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
1058-1330 1.00e-06

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


Pssm-ID: 341343 [Multi-domain]  Cd Length: 274  Bit Score: 52.09  E-value: 1.00e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1058 VGVGFSILSLAACLVVeAVVWKSVTKNRTSYMRH---TCIVNIAASLLvantWFIVVA---AIQDNRYILCKtacvaatf 1131
Cdd:cd15274    10 VGHSLSIATLLISLGI-FFFFRSLSCQRVTLHKNlflSYILNSIIIII----HLVAVVpngELVARNPVSCK-------- 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1132 FIHFFYL----SVFFWMLTLGLMLFYRLVF-ILHETSRSTqkaIAFCLGYGCPL---AISVITlgatqpREVYTRKNvCW 1203
Cdd:cd15274    77 ILHFIHQymmgCNYFWMLCEGIYLHTLIVVaVFAEKQRLM---WYYLLGWGFPLiptTIHAIT------RAVYYNDN-CW 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1204 LNwEDTKALLAFAIPALIIVVVN----ITITIVVITKIlrpsigdKPCKQEKSSLF-QISKSIGVLTPLLGLTwgFGLTT 1278
Cdd:cd15274   147 LS-SETHLLYIIHGPIMAALVVNffflLNIVRVLVTKL-------RETHEAESHMYlKAVKATLILVPLLGIQ--FVLFP 216
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 530381549 1279 VFPGTNLVFHI---IFAILNVFQGLFILLFGCLWDLKVQEAL---LNKFSLSRWSSQH 1330
Cdd:cd15274   217 WRPSGKILGKIydyVMHSLIHFQGFFVATIFCFCNGEVQATLkrqWNQYKIQFGVRFG 274
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
1052-1309 5.35e-06

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR114 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR97, GPR112, and GPR126. GPR114 is mainly found in granulocytes (polymorphonuclear leukocytes), and GPR114-transfected cells induced an increase in cAMP levels via coupling to G(s) protein. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320559 [Multi-domain]  Cd Length: 268  Bit Score: 49.75  E-value: 5.35e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVGFSILSLAACLVVEAVVWKSVTKNRTSYmrHtciVNIAASLLVANTWFI---VVAAIQDNryilckTACVA 1128
Cdd:cd15443     4 LTYISIVGCSISAAASLLTILLHFFSRKQPKDSTTRI--H---MNLLGSLFLLNGSFLlspPLATSQST------WLCRA 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1129 ATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRstQKAIAFC-LGYGCPLAISVITLGATqpREVYTRKNV------ 1201
Cdd:cd15443    73 AAALLHYSLLCCLTWMAIEGFHLYLLLVKVYNIYIR--RYVLKLCvLGWGLPALIVLLVLIFK--REAYGPHTIptgtgy 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1202 -----CWLNWEDTKALLAFAIpALIIVVVNITITIVVItKILR--PSIGDKPCKQEKSSLFQIsksIGvLTPLLGLTWGF 1274
Cdd:cd15443   149 qnasmCWITSSKVHYVLVLGY-AGLTSLFNLVVLAWVV-RMLRrlRSRKQELGERARRDWVTV---LG-LTCLLGTTWAL 222
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 530381549 1275 GLTTVfpGTNLVFHII-FAILNVFQGLFIllfgCLW 1309
Cdd:cd15443   223 AFFSF--GVFLIPQLFlFTIINSLYGFFI----CLW 252
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
1126-1314 7.92e-06

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: 341342 [Multi-domain]  Cd Length: 279  Bit Score: 49.18  E-value: 7.92e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1126 CVAATFFihffylsvffWMLTLGLMLFYRLVFILHETSRSTQkaIAFCLGYGCPLaISVITLGATqpREVYTRKNvCWLN 1205
Cdd:cd15268    96 CVAANYY----------WLLVEGVYLYTLLAFSVFSEQRIFR--LYLSIGWGVPL-LFVIPWGIV--KYLYEDEG-CWTR 159
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1206 WEDTKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSslFQISKSIGVLTPLLG---LTWGFGLTTVFPG 1282
Cdd:cd15268   160 NSNMNYWLIIRLPILFAIGVNFLIFIRVICIVVSKLKANLMCKTDIK--CRLAKSTLTLIPLLGtheVIFAFVMDEHARG 237
                         170       180       190
                  ....*....|....*....|....*....|....
gi 530381549 1283 TnLVFHIIFAILNV--FQGLFILLFGCLWDLKVQ 1314
Cdd:cd15268   238 T-LRFVKLFTELSFtsFQGLMVAILYCFVNNEVQ 270
SEA smart00200
Domain found in sea urchin sperm protein, enterokinase, agrin; Proposed function of regulating ...
179-281 1.24e-05

Domain found in sea urchin sperm protein, enterokinase, agrin; Proposed function of regulating or binding carbohydrate sidechains.


Pssm-ID: 214554  Cd Length: 121  Bit Score: 45.87  E-value: 1.24e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549    179 NVGFQEDLMNTSSALYRSYKTDLETAFRKGYG---ILPGFKGVTVTGFKSGSVVVTYEVKTTPPSleliHKANEQVVQSL 255
Cdd:smart00200   18 NLQYSPSLEDPSSEEYQELVRDVEKLLEQIYGktdLKPDFVGTEVIEFRNGSVVVDLGLLFNEGV----TNGQDVEEDLL 93
                            90       100
                    ....*....|....*....|....*..
gi 530381549    256 NQTYKMDYNS-FQAVTINESNFFVTPE 281
Cdd:smart00200   94 QVIKQAAYSLkITNVNVVDVLDPDSAD 120
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
1126-1321 1.25e-05

vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of seven-transmembrane G protein-coupled receptors; Vasoactive intestinal peptide (VIP) receptor 1 is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. VIP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320397 [Multi-domain]  Cd Length: 268  Bit Score: 48.70  E-value: 1.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1126 CVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIafCLGYGCPlaiSVITLGATQPReVYTRKNVCWLN 1205
Cdd:cd15269    77 CKAAMVFFQYCIMANFFWLLVEGLYLHTLLAVSFFSERKYFWWYI--LIGWGAP---SVFITAWSVAR-IYFEDVGCWDT 150
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1206 WEDTKALLAFAIPALIIVVVN----ITITIVVITKILRPSIGdkpcKQEKSSLFQISKSIGVLTPLLGLTwgFGLTTVFP 1281
Cdd:cd15269   151 IIESLLWWIIKTPILVSILVNfilfICIIRILVQKLHSPDIG----RNESSQYSRLAKSTLLLIPLFGIH--YIMFAFFP 224
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 530381549 1282 GT-----NLVFHIifaILNVFQGLFILLFGCLWDLKVQEALLNKF 1321
Cdd:cd15269   225 DNfkaevKLVFEL---ILGSFQGFVVAVLYCFLNGEVQAELKRKW 266
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
1125-1314 1.35e-05

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


Pssm-ID: 320401 [Multi-domain]  Cd Length: 285  Bit Score: 48.52  E-value: 1.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1125 ACVAATFFIHFFYLSVFFWMLTLGLMLfYRLVFILHETSrSTQKAIAFCLGYGCPLAISVITLGATQPREvytrKNVCWL 1204
Cdd:cd15273    90 VCKAITSLWQYFIIANYSWILMEGLYL-HNLIFLALFSD-ENNIILYILLGWGLPLIFVVPWIVARILFE----NSLCWT 163
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1205 NWEDTKALLAFAIPALIIVVVN----ITITIVVITKiLRPSIgdkpckQEKSSLFQ-ISKSIGVLTPLLGLTWGFGLTTV 1279
Cdd:cd15273   164 TNSNLLNFLIIRIPIMISVLINfilfLNIVRVLLVK-LRSSV------NEDSRRYKkWAKSTLVLVPLFGVHYTIFLILS 236
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 530381549 1280 F-PGTNLVFHIIF----AILNVFQGLFILLFGCLWDLKVQ 1314
Cdd:cd15273   237 YlDDTNEAVELIWlfcdQLFASFQGFFVALLYCFLNGEVR 276
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
1052-1314 2.10e-05

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: 47.90  E-value: 2.10e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1052 LDIISYVGVgfsILSLAACLVVEAVVWKSVTKNRTsymrHTCIV--NIAASLLVANTWFIVVAAIQDnryILCKTACVAA 1129
Cdd:cd15995     4 LTILTYVGC---IISALASVFTIAFYLCSRRKPRD----YTIYVhmNLLLAIFLLDTSFLISEPLAL---TGSEAACRAG 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLfYRLVFilhETSRSTQKAIAFCL---GYGCPLAISVITLGATQPR------------E 1194
Cdd:cd15995    74 GMFLHFSLLACLTWMGIEGYNL-YRLVV---EVFNTYVPHFLLKLcavGWGLPIFLVTLIFLVDQDNygpiilavhrspE 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1195 VYTRKNVCWLNWEDTKALLAFAIPALIIvVVNITITIVVITKILRpsigDKPCKQEKSSLFQIsksIGvLTPLLGLTWGF 1274
Cdd:cd15995   150 KVTYATICWITDSLISNITNLGLFSLVF-LFNMAMLATMVVEILR----LRPRTHKWSHVLTL---LG-LSLVLGIPWAL 220
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 530381549 1275 GLTTVFPGT-NLVFHIIFAILNVFQGLFILLFgcLWDLKVQ 1314
Cdd:cd15995   221 AFFSFASGTfQLVIVYLFTIINSLQGFLIFLW--YWSMVLQ 259
SEA pfam01390
SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed ...
170-258 2.66e-05

SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed function of regulating or binding carbohydrate side chains. Recently a proteolytic activity has been shown for a SEA domain.


Pssm-ID: 460188  Cd Length: 100  Bit Score: 44.54  E-value: 2.66e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549   170 VTLNMRVrLNVGFQEDLMNTSSALYRSYKTDLETAFRKGY---GILPGFKGVTVTGFKS--GSVVVTYEVKTTPPSLELi 244
Cdd:pfam01390    3 YTGSFKI-TNLQYTPDLGNPSSQEFKSLSRRIESLLNELFrnsSLRKQYIKSHVLRLRPdgGSVVVDVVLVFRFPSTEP- 80
                           90
                   ....*....|....*
gi 530381549   245 HKANEQVVQS-LNQT 258
Cdd:pfam01390   81 ALDREKLIEEiLRQT 95
I-set pfam07679
Immunoglobulin I-set domain;
285-351 4.11e-05

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 43.40  E-value: 4.11e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530381549   285 EGDTVSLVCE-KEVLSSNVSWRYEEQqlEIQNSSRFSIytalfNNMTSVSKLTIHNITPGDAGEYVCK 351
Cdd:pfam07679   14 EGESARFTCTvTGTPDPEVSWFKDGQ--PLRSSDRFKV-----TYEGGTYTLTISNVQPDDSGKYTCV 74
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
279-351 4.41e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 42.94  E-value: 4.41e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530381549   279 TPEIIFEGDTVSLVCE-KEVLSSNVSWRYEEQQLEIQNSSRFSIYTalfnnmtSVSKLTIHNITPGDAGEYVCK 351
Cdd:pfam13927    9 SSVTVREGETVTLTCEaTGSPPPTITWYKNGEPISSGSTRSRSLSG-------SNSTLTISNVTRSDAGTYTCV 75
7tm_classA_rhodopsin-like cd00637
rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor ...
1063-1233 6.54e-05

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: 410626 [Multi-domain]  Cd Length: 275  Bit Score: 46.51  E-value: 6.54e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1063 SILSLAACLVVEAVVWKSVTKNRTSYMrhtCIVNIAAS-LLVA--NTWFIVVAAIQdNRYILCKTACVAATFFIHFFYLS 1139
Cdd:cd00637     9 FVVGLVGNLLVILVILRNRRLRTVTNY---FILNLAVAdLLVGllVIPFSLVSLLL-GRWWFGDALCKLLGFLQSVSLLA 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1140 VffwMLTLGLMLFYRLVFILH-------ETSRSTQKAIAFCLGYGCPLAISVITLGATQPREVYTRKNVCWLNWEDTKA- 1211
Cdd:cd00637    85 S---ILTLTAISVDRYLAIVHplryrrrFTRRRAKLLIALIWLLSLLLALPPLLGWGVYDYGGYCCCCLCWPDLTLSKAy 161
                         170       180
                  ....*....|....*....|....*..
gi 530381549 1212 -----LLAFAIPALIIVVVNITITIVV 1233
Cdd:cd00637   162 tiflfVLLFLLPLLVIIVCYVRIFRKL 188
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
1058-1323 1.01e-04

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


Pssm-ID: 320651 [Multi-domain]  Cd Length: 280  Bit Score: 45.69  E-value: 1.01e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1058 VGVGFSILSLAACLVVEAVVWK-SVTKNRTSYMRHTCIVNIAASLLVANT-----WFIVVAAIQDNRYILCKTA---CVA 1128
Cdd:cd15985    10 VGYTLSLLTLVSALLILTSIRKlHCTRNYIHANLFASFILRAVSVIVKDTllerrWGREIMRVADWGELLSHKAaigCRM 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1129 ATFFIHFFYLSVFFWMLTLGLMLFYRLV-FILHETSRSTqkaIAFCLGYGCPLAISVITLGATqprevYTRKNV-CWLNW 1206
Cdd:cd15985    90 AQVVMQYCILANHYWFFVEAVYLYKLLIgAVFSEKNYYL---LYLYLGWGTPVLFVVPWMLAK-----YLKENKeCWALN 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1207 EDTKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKpcKQEKSSLFQISKSIGVLTPLLGL---TWGFGLTTVFPGT 1283
Cdd:cd15985   162 ENMAYWWIIRIPILLASLINLLIFMRILKVILSKLRANQ--KGYADYKLRLAKATLTLIPLFGIhevVFIFATDEQTTGI 239
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 530381549 1284 NLVFHIIFAI-LNVFQGLFILLFGCLWDLKVQEALLNKFSL 1323
Cdd:cd15985   240 LRYIKVFFTLfLNSFQGFLVAVLYCFANKEVKSELLKKWRL 280
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
1118-1325 1.09e-04

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


Pssm-ID: 320650 [Multi-domain]  Cd Length: 290  Bit Score: 45.71  E-value: 1.09e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1118 RYILCKtacVAATFFIHFFYLSvFFWMLTLGLMLfYRLVFILHETSRSTQKAIAFcLGYGCPlAISVITLGATQPREVYT 1197
Cdd:cd15984    91 QFVGCK---VAVTFFLYFLATN-YYWILVEGLYL-HSLIFMAFFSEKKYLWGFTL-FGWGLP-AVFVTIWASVRATLADT 163
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1198 RknvCW-LNWEDTKALLAfaIPALIIVVVN----ITITIVVITKILRPSIGDKPCKQEKSSLFqisKSIGVLTPLLGLTW 1272
Cdd:cd15984   164 G---CWdLSAGNLKWIIQ--VPILAAIVVNfilfINIVRVLATKLRETNAGRCDTRQQYRKLL---KSTLVLMPLFGVHY 235
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530381549 1273 GFGLTTVF---PGTNLVFHIIFAIL-NVFQGLFILLFGCLWDLKVQEALlnKFSLSR 1325
Cdd:cd15984   236 IVFMAMPYtevSGILWQVQMHYEMLfNSFQGFFVAIIYCFCNGEVQAEI--KKSWSR 290
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
1124-1323 2.21e-04

glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon-like peptide-2 receptor (GLP2R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor (GCGR) and GLP1R. GLP2R is activated by glucagon-like peptide 2, which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. GLP2R belongs to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320394 [Multi-domain]  Cd Length: 280  Bit Score: 44.74  E-value: 2.21e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1124 TACVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAfcLGYGCPLaISVITLGATQpreVYTRKNVCW 1203
Cdd:cd15266    85 TSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYML--IGWGTPV-LFVVPWGVAK---ILLENTGCW 158
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1204 LNWEDTKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSslFQISKSIGVLTPLLG---LTWGFGLTTVF 1280
Cdd:cd15266   159 GRNENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYK--YRLARSTLVLIPLLGiheVVFSFITDEQV 236
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 530381549 1281 PG-TNLVFHIIFAILNVFQGLFILLFGCLWDLKVQEALLNKFSL 1323
Cdd:cd15266   237 EGfSRHIRLFIQLTLSSFQGFLVAVLYCFANGEVKAELKKRWQL 280
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
1131-1314 7.18e-04

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


Pssm-ID: 320400 [Multi-domain]  Cd Length: 285  Bit Score: 43.15  E-value: 7.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1131 FFIHFFYLSV--FFWMLTLGLMLfYRLVFI--LHETSRSTQKAIafcLGYGCPLAISV--ITLGATQPREVytrknvCWL 1204
Cdd:cd15272    93 FFTMFNYILGanYMWIFVEGLYL-HMLIFVavFSENSRVKWYIL---LGWLSPLLFVLpwVFVRATLEDTL------CWN 162
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1205 NWEDTKALLAFAIPALIIVVVN----ITITIVVITKiLRPSIGDK--PCKQEKsslfqISKSIGVLTPLLGLTW----GF 1274
Cdd:cd15272   163 TNTNKGYFWIIRGPIVISIAINflffINIVRVLFTK-LKASNTQEsrPFRYRK-----LAKSTLVLIPLFGVHYmvfvVL 236
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 530381549 1275 GLTTVFPGTNLVFHIIFAILNVFQGLFILLFGCLWDLKVQ 1314
Cdd:cd15272   237 PDSMSSDEAELVWLYFEMFFNSFQGFIVALLFCFLNGEVQ 276
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
517-602 7.94e-04

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 39.80  E-value: 7.94e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549    517 PDPISVSEGQNFSIKCISDVSNYDEVYWNTSAGIKIYQRFYTTRRYlDGAESVLTVKTSTREWNGTYHCIFRYKNSYSIA 596
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSR-SGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                    ....*.
gi 530381549    597 TKDVIV 602
Cdd:smart00410   80 GTTLTV 85
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
1060-1320 8.89e-04

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


Pssm-ID: 320395 [Multi-domain]  Cd Length: 281  Bit Score: 42.89  E-value: 8.89e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1060 VGFSiLSLAACLVVEAVVwksVTKNRTSYMRHTCIVNIAASLLVANTWFIVVAAIQDNRYIL--------------CKTA 1125
Cdd:cd15267    12 VGYS-LSLGALLLALAIL---GGFSKLHCMRNAIHMNLFASFILKASSVLVIDGLLRTRYSQkieddlsstwlsdeAVAG 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1126 CVAATFFIHFFYLSVFFWMLTLGLMLfYRLVFILHETSRSTQKaIAFCLGYGCPLAISVITLGATqprevYTRKNV-CWL 1204
Cdd:cd15267    88 CRVAAVFMQYGIVANYCWLLVEGIYL-HNLLVLAVFPERSYFS-LYLCIGWGAPALFVVPWVVVK-----CLYENVqCWT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1205 NWEDTKALLAFAIPALIIVVVNITITIVVItKILRPSIgDKPCKQEKSSLFQISKSIGVLTPLLGL---TWGFGLTTVFP 1281
Cdd:cd15267   161 SNDNMGFWWILRFPVFLAILINFFIFVRII-QILVSKL-RARQMHYTDYKFRLAKSTLTLIPLLGIhevVFAFVTDEHAQ 238
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 530381549 1282 GTNLVFHIIFAI-LNVFQGLFILLFGCLWDLKVQEALLNK 1320
Cdd:cd15267   239 GTLRSAKLFFDLfLSSFQGLLVAVLYCFLNKEVQSELRRR 278
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
1054-1314 9.18e-04

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


Pssm-ID: 320398 [Multi-domain]  Cd Length: 268  Bit Score: 42.86  E-value: 9.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1054 IISYVGVGFSILSLAACLVVeAVVWKSVTKNRtSYMrHTCIvnIAASLLVANTWFIVVAAIQDNRYI----LCKTACVAA 1129
Cdd:cd15270     6 IIYTVGYSISIVSLCVAVAI-LVAFRRLHCPR-NYI-HIQL--FFTFILKAIAVFIKDAALFQEDDTdhcsMSTVLCKVS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1130 TFFIHFFYLSVFFWMLTLGLMLFYRLVFILhetSRSTQKAIAFCL-GYGCPLAISVITLGAtqprEVYTRKNVCWLNWED 1208
Cdd:cd15270    81 VVFCHYCVMTNFFWLLVEAVYLNCLLASSF---PRGKRYFWWLVLlGWGLPTLCTGTWILC----KLYFEDTECWDINND 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1209 TKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSSLFQISKSIGVLTPLLGLTW-GFGLTTVFPGTNLVF 1287
Cdd:cd15270   154 SPYWWIIKGPIVISVGVNFLLFLNIIRILLKKLDPRQINFNNSAQYRRLSKSTLLLIPLFGTHYiIFNFLPDYAGLGIRL 233
                         250       260
                  ....*....|....*....|....*..
gi 530381549 1288 HIIFAiLNVFQGLFILLFGCLWDLKVQ 1314
Cdd:cd15270   234 YLELC-LGSFQGFIVAVLYCFLNQEVQ 259
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
513-586 1.19e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 39.09  E-value: 1.19e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530381549   513 LTITPDPISVSEGQNFSIKCISDVSNYDEVYWNTSAGIKIYQRfyTTRRYLDGAESVLTVKTSTREWNGTYHCI 586
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGS--TRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
1104-1307 1.30e-03

G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR123 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, and also includes orphan receptors GPR124 and GPR125. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells, yet its biological function remains to be determined. Adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320666 [Multi-domain]  Cd Length: 275  Bit Score: 42.25  E-value: 1.30e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1104 ANTWFIVVAAIQDNRY-ILCKtacvAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIA-------FCLG 1175
Cdd:cd16000    51 ALTFAVFAGGINRTKYpIICQ----AVGIVLHYSTLSTMLWIGVTARNIYKQVTKKPHLCQDTDQPPYPkqpllrfYLVS 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1176 YGCPLAISVITlGATQPREVYTRKN---VCWLNWEdtKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKS 1252
Cdd:cd16000   127 GGVPFIICGIT-AATNINNYGTEDEdtpYCWMAWE--PSLGAFYGPVAFIVLVTCIYFLCTYVQLRRHPERKYELKNEHS 203
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530381549 1253 SLFQISKSIGVLTpLLGLTWGFGLTTVFPG--TNLVFHIIFAILNVFQGLFILLFGC 1307
Cdd:cd16000   204 FKAQLRAAAFTLF-LFTATWAFGALAVSQGhfLDMIFSCLYGAFCVTLGLFILIHHC 259
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
1124-1317 2.65e-03

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


Pssm-ID: 341353 [Multi-domain]  Cd Length: 279  Bit Score: 41.27  E-value: 2.65e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1124 TACVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHETSRSTQKAIAfcLGYGCPLaISVITLGATQprevYTRKNV-C 1202
Cdd:cd15929    84 LGCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLL--LGWGAPV-LFVVPWGIVK----YLYENTgC 156
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1203 WLNWEDTKALLAFAIPALIIVVVNITITIVVITKILRPSIGDKPCKQEKSslFQISKSIGVLTPLLG---LTWGFGLTTV 1279
Cdd:cd15929   157 WTRNDNMAYWWIIRLPILLAILINFFIFVRILKILVSKLRANQMCKTDYK--FRLAKSTLTLIPLLGvheVVFAFVTDEQ 234
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 530381549 1280 FPGTnLVFHIIFA--ILNVFQGLFILLFGCLWDLKVQEAL 1317
Cdd:cd15929   235 ARGT-LRFIKLFFelFLSSFQGLLVAVLYCFANKEVQSEL 273
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
283-352 3.07e-03

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 37.94  E-value: 3.07e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530381549   283 IFEGDTVSLVCEKEVLSSN--VSWRYEEQQLEiqnssrFSIYTALFNNMTSVSKLTIHNITPGDAGEYVCKL 352
Cdd:pfam00047    8 VLEGDSATLTCSASTGSPGpdVTWSKEGGTLI------ESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVV 73
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
1126-1318 3.29e-03

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


Pssm-ID: 320389 [Multi-domain]  Cd Length: 282  Bit Score: 41.20  E-value: 3.29e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1126 CVAATFFIHFFYLSVFFWMLTLGLMLFYRLVFILHetsRSTQKAIAFC-LGYGCPLAISVITLGATQpreVYTRKNVCWL 1204
Cdd:cd15261    88 CEGFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVF---SGKPNYLFYYiLGWGIPIVHTSAWAIVTL---IKMKVNRCWF 161
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381549 1205 NWEDTKALLAFAIPALIIVVVN----ITITIVVITKiLRpsigdkpcKQEKSSLFQISKSIG---VLTPLLGLTwGFGLT 1277
Cdd:cd15261   162 GYYLTPYYWILEGPRLAVILINlfflLNIIRVLVSK-LR--------ESHSREIEQVRKAVKaaiVLLPLLGIT-NILQM 231
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 530381549 1278 TVFPGTNLVFHiiFAI-------LNVFQGLFILLFGCLWDLKVQEALL 1318
Cdd:cd15261   232 IPPPLTSVIVG--FAVwsysthfLTSFQGFFVALIYCFLNGEVKNVLK 277
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
289-351 5.09e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 36.92  E-value: 5.09e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530381549  289 VSLVCE-KEVLSSNVSWRYEEQQLEIQNSSRFSIYTalfnnmtSVSKLTIHNITPGDAGEYVCK 351
Cdd:cd00096     1 VTLTCSaSGNPPPTITWYKNGKPLPPSSRDSRRSEL-------GNGTLTISNVTLEDSGTYTCV 57
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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