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Conserved domains on  [gi|341940782|sp|Q8VEC3|]
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RecName: Full=Adhesion G-protein coupled receptor F1; AltName: Full=G protein-coupled receptor 110; Flags: Precursor

Protein Classification

SEA and GPS domain-containing protein( domain architecture ID 12018329)

protein containing domains SEA, GPS, and 7tm_GPCRs

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
584-847 6.50e-134

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


The actual alignment was detected with superfamily member cd15932:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 268  Bit Score: 401.31  E-value: 6.50e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 584 KWITYIGLSISIASLILCLIIESLFWKQTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPSGVCVAAVFFTH 663
Cdd:cd15932    5 DYITYVGLGISILSLVLCLIIEALVWKSVTKNKTSYMRHVCLVNIALSLLIADIWFIIGAAISTPPNPSPACTAATFFIH 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 664 FFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQPSNSYKRNDVCWLNWsDKSKPLL 743
Cdd:cd15932   85 FFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITVAATAPQGGYTRKGVCWLNW-DKTKALL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 744 AFVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMANSHNLAWHVLFAL 823
Cdd:cd15932  164 AFVIPALAIVVVNFIILIVVIFKLLRPSVGERPSKDEKNALVQIGKSVAILTPLLGLTWGFGLGTMIDPKSLAFHIIFAI 243
                        250       260
                 ....*....|....*....|....
gi 341940782 824 LNAFQGFFIFCFGILLDTKLRQLL 847
Cdd:cd15932  244 LNSFQGFFILVFGTLLDSKVREAL 267
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
530-571 2.71e-13

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: 64.72  E-value: 2.71e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 341940782   530 PRCVFWDFSQLQWSNAGCQLVNETLDTVLCRCSHLTSFSMLM 571
Cdd:smart00303   3 PICVFWDESSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
SEA super family cl02507
SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed ...
153-232 3.75e-04

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 pfam01390:

Pssm-ID: 470595  Cd Length: 100  Bit Score: 40.68  E-value: 3.75e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  153 GTFEI-DEKFPEDLWNSSSDVYAHYTVGIENQLKEAYRRV---HGFESVRVTQFRK--GSIVVGYEVTGSTSPPELLFAI 226
Cdd:pfam01390   5 GSFKItNLQYTPDLGNPSSQEFKSLSRRIESLLNELFRNSslrKQYIKSHVLRLRPdgGSVVVDVVLVFRFPSTEPALDR 84

                  ....*.
gi 341940782  227 EQEAEK 232
Cdd:pfam01390  85 EKLIEE 90
 
Name Accession Description Interval E-value
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
584-847 6.50e-134

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: 401.31  E-value: 6.50e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 584 KWITYIGLSISIASLILCLIIESLFWKQTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPSGVCVAAVFFTH 663
Cdd:cd15932    5 DYITYVGLGISILSLVLCLIIEALVWKSVTKNKTSYMRHVCLVNIALSLLIADIWFIIGAAISTPPNPSPACTAATFFIH 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 664 FFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQPSNSYKRNDVCWLNWsDKSKPLL 743
Cdd:cd15932   85 FFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITVAATAPQGGYTRKGVCWLNW-DKTKALL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 744 AFVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMANSHNLAWHVLFAL 823
Cdd:cd15932  164 AFVIPALAIVVVNFIILIVVIFKLLRPSVGERPSKDEKNALVQIGKSVAILTPLLGLTWGFGLGTMIDPKSLAFHIIFAI 243
                        250       260
                 ....*....|....*....|....
gi 341940782 824 LNAFQGFFIFCFGILLDTKLRQLL 847
Cdd:cd15932  244 LNSFQGFFILVFGTLLDSKVREAL 267
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
586-832 8.39e-24

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: 101.59  E-value: 8.39e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  586 ITYIGLSISIASLILCLIIESLFwkqtkRSQTSyTRNICLVNIAVSLLIADVWFIIAATV-----DPSVSPSGVCVAAVF 660
Cdd:pfam00002   7 IYTVGYSLSLVALLLAIAIFLLF-----RKLHC-TRNYIHLNLFASFILRALLFLVGDAVlfnkqDLDHCSWVGCKVVAV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  661 FTHFFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIgfCLGYGCPLLISIITLAVTqpSNSYKRNDVCWLNwsdKSK 740
Cdd:pfam00002  81 FLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYL--LIGWGVPALVVGIWAGVD--PKGYGEDDGCWLS---NEN 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  741 PLL-AFVVPALTIVAVNLVVVLLVLR----KLWRPAVGERlnqdDKATAIRMGKSLLVLTPLLGLTWGFGIGTMA--NSH 813
Cdd:pfam00002 154 GLWwIIRGPILLIILVNFIIFINIVRilvqKLRETNMGKS----DLKQYRRLAKSTLLLLPLLGITWVFGLFAFNpeNTL 229
                         250
                  ....*....|....*....
gi 341940782  814 NLAWHVLFALLNAFQGFFI 832
Cdd:pfam00002 230 RVVFLYLFLILNSFQGFFV 248
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
530-571 2.71e-13

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: 64.72  E-value: 2.71e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 341940782   530 PRCVFWDFSQLQWSNAGCQLVNETLDTVLCRCSHLTSFSMLM 571
Cdd:smart00303   3 PICVFWDESSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
530-570 3.70e-12

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: 61.55  E-value: 3.70e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 341940782  530 PRCVFWDFSQLQ---WSNAGCQLVNETLDTVLCRCSHLTSFSML 570
Cdd:pfam01825   1 PQCVFWDFTNSTtgrWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
SEA pfam01390
SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed ...
153-232 3.75e-04

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: 40.68  E-value: 3.75e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  153 GTFEI-DEKFPEDLWNSSSDVYAHYTVGIENQLKEAYRRV---HGFESVRVTQFRK--GSIVVGYEVTGSTSPPELLFAI 226
Cdd:pfam01390   5 GSFKItNLQYTPDLGNPSSQEFKSLSRRIESLLNELFRNSslrKQYIKSHVLRLRPdgGSVVVDVVLVFRFPSTEPALDR 84

                  ....*.
gi 341940782  227 EQEAEK 232
Cdd:pfam01390  85 EKLIEE 90
 
Name Accession Description Interval E-value
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
584-847 6.50e-134

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: 401.31  E-value: 6.50e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 584 KWITYIGLSISIASLILCLIIESLFWKQTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPSGVCVAAVFFTH 663
Cdd:cd15932    5 DYITYVGLGISILSLVLCLIIEALVWKSVTKNKTSYMRHVCLVNIALSLLIADIWFIIGAAISTPPNPSPACTAATFFIH 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 664 FFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQPSNSYKRNDVCWLNWsDKSKPLL 743
Cdd:cd15932   85 FFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITVAATAPQGGYTRKGVCWLNW-DKTKALL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 744 AFVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMANSHNLAWHVLFAL 823
Cdd:cd15932  164 AFVIPALAIVVVNFIILIVVIFKLLRPSVGERPSKDEKNALVQIGKSVAILTPLLGLTWGFGLGTMIDPKSLAFHIIFAI 243
                        250       260
                 ....*....|....*....|....
gi 341940782 824 LNAFQGFFIFCFGILLDTKLRQLL 847
Cdd:cd15932  244 LNSFQGFFILVFGTLLDSKVREAL 267
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
585-850 9.11e-96

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: 302.11  E-value: 9.11e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISIASLILCLIIESLFWKQTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSP--SGVCVAAVFFT 662
Cdd:cd15254    6 YITYIGLSISILSLAICIVIESLVWKSVTKNRTSYMRHVCILNIAVSLLIADIWFIVVAAIQDQNYAvnGNVCVAATFFI 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 663 HFFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQPSNSYKRNDVCWLNWSDkSKPL 742
Cdd:cd15254   86 HFFYLCVFFWMLALGLMLFYRLVFILHDTSKTIQKAVAFCLGYGCPLIISVITIAVTLPRDSYTRKKVCWLNWED-SKAL 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 743 LAFVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMANSHNLAWHVLFA 822
Cdd:cd15254  165 LAFVIPALIIVAVNSIITVVVIVKILRPSIGEKPSKQERSSLFQIIKSIGVLTPLLGLTWGFGLATVIKGSSIVFHILFT 244
                        250       260
                 ....*....|....*....|....*...
gi 341940782 823 LLNAFQGFFIFCFGILLDTKLRQLLSNK 850
Cdd:cd15254  245 LLNAFQGLFILVFGTLWDKKVQEALLNK 272
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
585-847 3.35e-89

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: 284.42  E-value: 3.35e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISIASLILCLIIESLFWKQTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPSGVCVAAVFFTHF 664
Cdd:cd15994    6 YITRIGLGLSIFSLALCLTIEAVVWSHVTKTEITYMRHVCIVNIATSLLIADVWFILASIVHNTALNYPLCVAATFFLHF 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQPSNSYKRNDVCWLNWsDKSKPLLA 744
Cdd:cd15994   86 FYLSLFFWMLTKALLILYGILLVFFKITKSVFIATAFSIGYGCPLVIAVLTVAITEPKKGYLRPEACWLNW-DETKALLA 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 745 FVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATaIRMGKSLLVLTPLLGLTWGFGIGTMANSHNLAWHVLFALL 824
Cdd:cd15994  165 FIIPALSIVVVNLIVVGVVVVKTQRSSIGESCKQDVSNI-IRISKNVAILTPLLGLTWGFGLATIIDSRSLPFHIIFALL 243
                        250       260
                 ....*....|....*....|...
gi 341940782 825 NAFQGFFIFCFGILLDTKLRQLL 847
Cdd:cd15994  244 NAFQGFFILLFGTILDRKIRIAL 266
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
586-851 1.24e-67

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: 226.57  E-value: 1.24e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFWKQTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATvdPSVSP-SGVCVAAVFFTHF 664
Cdd:cd15253    7 LSQVGLGASILALLLCLGIYRLVWRSVVRNKISYFRHMTLVNIAFSLLLADTCFLGATF--LSAGHeSPLCLAAAFLCHF 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQPSNSYKRNDVCWLNwsDKSKPLLA 744
Cdd:cd15253   85 FYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVTLGYLCPLLIAAATVAYYYPKRQYLHEGACWLN--GESGAIYA 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 745 FVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMANSHNLAWHVLFALL 824
Cdd:cd15253  163 FSIPVLAIVLVNLLVLFVVLMKLMRPSVSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLTGESSQVSHYGFAIL 242
                        250       260
                 ....*....|....*....|....*..
gi 341940782 825 NAFQGFFIFCFGILLDTKLRQLLSNKL 851
Cdd:cd15253  243 NAFQGVFILLFGCLMDKKVREALLKRL 269
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
585-846 1.52e-40

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: 150.03  E-value: 1.52e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISIASLILCLIIESLFWKQTKRsqtsyTRNICLVNIAVSLLIADVWFIIAATVDPSvspSGVCVAAVFFTHF 664
Cdd:cd15040    6 IITYIGCGLSLLGLLLTIITYILFRKLRKR-----KPTKILLNLCLALLLANLLFLFGINSTDN---PVLCTAVAALLHY 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGILLAYRIILVFHHMaLTTMMAIGFCLGYGCPLLISIITLAVTqPSNSYKRNDVCWLnwSDKSKPLLA 744
Cdd:cd15040   78 FLLASFMWMLVEALLLYLRLVKVFGTY-PRHFILKYALIGWGLPLIIVIITLAVD-PDSYGNSSGYCWL--SNGNGLYYA 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 745 FVVPALTIVAVNLVVVLLVLRKLWRPAVgeRLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMANSHnLAWHVLFALL 824
Cdd:cd15040  154 FLGPVLLIILVNLVIFVLVLRKLLRLSA--KRNKKKRKKTKAQLRAAVSLFFLLGLTWIFGILAIFGAR-VVFQYLFAIF 230
                        250       260
                 ....*....|....*....|..
gi 341940782 825 NAFQGFFIFCFGILLDTKLRQL 846
Cdd:cd15040  231 NSLQGFFIFIFHCLRNKEVRKA 252
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
585-847 1.22e-34

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


Pssm-ID: 410627 [Multi-domain]  Cd Length: 260  Bit Score: 133.11  E-value: 1.22e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISIASLILCLIIESLFWKQTKrsqtsyTRNICLVNIAVSLLIADVWFIIAATVDPSVSPSGvCVAAVFFTHF 664
Cdd:cd13952    6 IITYIGCSLSLVGLLLTIITYLLFPKLRN------LRGKILINLCLSLLLAQLLFLIGQLLTSSDRPVL-CKALAILLHY 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGILLAYRIILVFHHMaLTTMMAIGFCLGYGCPLLISIITLAVTQPSNSYKR---NDVCWLNwSDKSKp 741
Cdd:cd13952   79 FLLASFFWMLVEAFDLYRTFVKVFGSS-ERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPgygGEYCWLS-NGNAL- 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 742 LLAFVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIR----------MGksllvltpllgLTWGFGIGTMAN 811
Cdd:cd13952  156 LWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSDRKQlraylklfplMG-----------LTWIFGILAPFV 224
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 341940782 812 SHNLAWHVLFALLNAFQGFFIFCFGILLDTKLRQLL 847
Cdd:cd13952  225 GGSLVFWYLFDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
586-847 3.04e-32

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: 125.90  E-value: 3.04e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFwkqtkrSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPsgvCVAAVFFTHFF 665
Cdd:cd15933    7 ISYIGCGISIACLALTLIIFLVL------RVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGNKVA---CKVVAILLHFF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHHmalTTMMAIGFCLGYGCPLLISIITLAVTqpSNSYKRNDVCWLNWSDKSKplLAF 745
Cdd:cd15933   78 FMAAFSWMLVEGLHLYLMIVKVFNY---KSKMRYYYFIGWGLPAIIVAISLAIL--FDDYGSPNVCWLSLDDGLI--WAF 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 746 VVPALTIVAVNLVVVLLVLRKLWR-PAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTmANSHNLAWHVLFALL 824
Cdd:cd15933  151 VGPVIFIITVNTVILILVVKITVSlSTNDAKKSQGTLAQIKSTAKASVVLLPILGLTWLFGVLV-VNSQTIVFQYIFVIL 229
                        250       260
                 ....*....|....*....|...
gi 341940782 825 NAFQGFFIFCFGILLDTKLRQLL 847
Cdd:cd15933  230 NSLQGLMIFLFHCVLNSEVRSAF 252
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
586-850 1.83e-27

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: 112.33  E-value: 1.83e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFWK-QTKRSQTSYTRniclVNIAVSLLIADVWFIIAATVDPSVSPsgvCVAAVFFTHF 664
Cdd:cd15256    7 ITYVGCSLSIFCLAITLVTFAVLSSvSTIRNQRYHIH----ANLSFAVLVAQILLLISFRFEPGTLP---CKIMAILLHF 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGfcLGYGCPLLISIITLavTQPSNSYKRNDVCWLnwSDKSKPLLA 744
Cdd:cd15256   80 FFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYG--IGWGSPLLICIISL--TSALDSYGESDNCWL--SLENGAIWA 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 745 FVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIgTMANSHNLAWHVLFALL 824
Cdd:cd15256  154 FVAPALFVIVVNIGILIAVTRVISRISADNYKVHGDANAFKLTAKAVAVLLPILGSSWVFGV-LAVNTHALVFQYMFAIF 232
                        250       260
                 ....*....|....*....|....*.
gi 341940782 825 NAFQGFFIFCFGILLDTKLRQLLSNK 850
Cdd:cd15256  233 NSLQGFFIFLFHCLLNSEVRAAFKHK 258
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
586-849 2.69e-25

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: 106.19  E-value: 2.69e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFwKQTKRSQTSYTRNICLvniavSLLIADVWFIIAATvdpSVSPSGVCVAAVFFTHFF 665
Cdd:cd15440    7 ITYIGCIISIVCLLLAFITFTCF-RNLQCDRNTIHKNLCL-----CLLIAEIVFLLGID---QTENRTLCGVIAGLLHYF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHhmALTTMMAIGFCLGYGCPLLISIITLAVTqpSNSYKRNDVCWLNWSDKSkpLLAF 745
Cdd:cd15440   78 FLAAFSWMLLEGFQLYVMLVEVFE--PEKSRIKWYYLFGYGLPALIVAVSAGVD--PTGYGTEDHCWLSTENGF--IWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 746 VVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQD-DKATAIRMG-KSLLVLTPLLGLTWGFGIGTMaNSHNLAWHVLFAL 823
Cdd:cd15440  152 VGPVIVVLLANLVFLGMAIYVMCRHSSRSASKKDaSKLKNIRGWlKGSIVLVVLLGLTWTFGLLFI-NQESIVMAYIFTI 230
                        250       260
                 ....*....|....*....|....*.
gi 341940782 824 LNAFQGFFIFCFGILLDTKLRQLLSN 849
Cdd:cd15440  231 LNSLQGLFIFIFHCVLNEKVRKELRR 256
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
586-832 8.39e-24

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: 101.59  E-value: 8.39e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  586 ITYIGLSISIASLILCLIIESLFwkqtkRSQTSyTRNICLVNIAVSLLIADVWFIIAATV-----DPSVSPSGVCVAAVF 660
Cdd:pfam00002   7 IYTVGYSLSLVALLLAIAIFLLF-----RKLHC-TRNYIHLNLFASFILRALLFLVGDAVlfnkqDLDHCSWVGCKVVAV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  661 FTHFFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIgfCLGYGCPLLISIITLAVTqpSNSYKRNDVCWLNwsdKSK 740
Cdd:pfam00002  81 FLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYL--LIGWGVPALVVGIWAGVD--PKGYGEDDGCWLS---NEN 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  741 PLL-AFVVPALTIVAVNLVVVLLVLR----KLWRPAVGERlnqdDKATAIRMGKSLLVLTPLLGLTWGFGIGTMA--NSH 813
Cdd:pfam00002 154 GLWwIIRGPILLIILVNFIIFINIVRilvqKLRETNMGKS----DLKQYRRLAKSTLLLLPLLGITWVFGLFAFNpeNTL 229
                         250
                  ....*....|....*....
gi 341940782  814 NLAWHVLFALLNAFQGFFI 832
Cdd:pfam00002 230 RVVFLYLFLILNSFQGFFV 248
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
586-852 5.17e-22

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: 96.55  E-value: 5.17e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFwkqtkRSQTSYTRNIcLVNIAVSLLIADVWFIIAATvdpSVSPSGVCVAAVFFTHFF 665
Cdd:cd15441    7 VTYIGIGISLVLLVIAFLVLSCL-----RGLQSNSNSI-HKNLVACLLLAELLFLLGIN---QTENLFPCKLIAILLHYF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLaYRIiLVFHHMALTTMMAIGFCLGYGCPLLISIITLAVtQPSnSYKRNDVCWLnwsDKSKPLL-A 744
Cdd:cd15441   78 YLSAFSWLLVESLHL-YRM-LTEPRDINHGHMRFYYLLGYGIPAIIVGLSVGL-RPD-GYGNPDFCWL---SVNETLIwS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 745 FVVPALTIVAVNLVVVLLVLRKLWRpavgeRLNQDDKATAIRMG-KSLLVLTPLLGLTWGFGIgTMANSHNLAWHVLFAL 823
Cdd:cd15441  151 FAGPIAFVIVITLIIFILALRASCT-----LKRHVLEKASVRTDlRSSFLLLPLLGATWVFGL-LAVNEDSELLHYLFAG 224
                        250       260
                 ....*....|....*....|....*....
gi 341940782 824 LNAFQGFFIFCFGILLDTKLRQLLSNKLT 852
Cdd:cd15441  225 LNFLQGLFIFLFYCIFNKKVRRELKNALL 253
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
586-845 3.46e-18

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: 85.25  E-value: 3.46e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNIClvniaVSLLIADVWFIIAatVDPSVSPSgVCVAAVFFTHFF 665
Cdd:cd15252    7 ITQVGIIISLVCLAIC-IFTFWFFRGLQSDRTTIHKNLC-----ISLFLAELVFLIG--INTTTNKI-FCSVIAGLLHYF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHhmALTTMMAIGFCLGYGCPLLISIITLAVTqpSNSYKRNDVCWLnwSDKSKPLLAF 745
Cdd:cd15252   78 FLAAFAWMFIEGIQLYLMLVEVFE--NEGSRHKNFYIFGYGSPAVIVGVSAALG--YRYYGTTKVCWL--STENYFIWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 746 VVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIgTMANSHNLAWHVLFALLN 825
Cdd:cd15252  152 IGPATLIILLNLIFLGVAIYKMFRHTAGLKPEVSCLENIRSWARGAIALLFLLGLTWIFGV-LHINHASVVMAYLFTVSN 230
                        250       260
                 ....*....|....*....|
gi 341940782 826 AFQGFFIFCFGILLDTKLRQ 845
Cdd:cd15252  231 SLQGMFIFLFHCVLSRKVRK 250
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
586-845 1.02e-16

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: 80.96  E-value: 1.02e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNICLvniavSLLIADVWFIIAATVDPSVSPSGVcVAAVFftHFF 665
Cdd:cd15438    7 ITKVGLSVSLFCLFLC-ILTFLFCRSIRGTRNTIHLHLCL-----SLFLAHLIFLLGINNTNNQVACAV-VAGLL--HYF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVF--HHMALTTMMAIgfclGYGCPLLISIITLAVTqpSNSYKRNDVCWLNWSDKSkpLL 743
Cdd:cd15438   78 FLAAFCWMSLEGVELYLMVVQVFntQSLKKRYLLLI----GYGVPLVIVAISAAVN--SKGYGTQRHCWLSLERGF--LW 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 744 AFVVPALTIVAVNLVVVLLVLRKLWRPAvgERLNQD-DKATAIR-MGKSLLVLTPLLGLTWGFGIGTMaNSHNLAWHVLF 821
Cdd:cd15438  150 SFLGPVCLIILVNAIIFVITVWKLAEKF--SSINPDmEKLRKIRaLTITAIAQLCILGCTWIFGFFQF-SDSTLVMSYLF 226
                        250       260
                 ....*....|....*....|....
gi 341940782 822 ALLNAFQGFFIFCFGILLDTKLRQ 845
Cdd:cd15438  227 TILNSLQGLFIFLLHCLLSKQVRE 250
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
584-833 1.05e-16

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: 81.12  E-value: 1.05e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 584 KWITYIGLSISIASLILCLIIESLFwkqtkrsqtSYTRNI---CLVNIAVSLLIADVWFIIAATVdpSVSPSGVCVAAVF 660
Cdd:cd15039    5 GILTLIGLIISLVFLLLTLAVYALL---------PELRNLhgkCLMCLVLSLFVAYLLLLIGQLL--SSGDSTLCVALGI 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 661 FTHFFYLAVFFWMLVLG--ILLAYRIILVFHHMALTTMMAIGFCL-GYGCPLLISIITLAVTQ-PSNSYKR----NDVCW 732
Cdd:cd15039   74 LLHFFFLAAFFWLNVMSfdIWRTFRGKRSSSSRSKERKRFLRYSLyAWGVPLLLVAVTIIVDFsPNTDSLRpgygEGSCW 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 733 LNwSDKSKpLLAFVVPALTIVAVNLVVVLLVLRKLWR----PAVGERLNQDDKAT-------AIRMGksllvltpllgLT 801
Cdd:cd15039  154 IS-NPWAL-LLYFYGPVALLLLFNIILFILTAIRIRKvkkeTAKVQSRLRSDKQRfrlylklFVIMG-----------VT 220
                        250       260       270
                 ....*....|....*....|....*....|...
gi 341940782 802 WGFGIGT-MANSHNLAWHVlFALLNAFQGFFIF 833
Cdd:cd15039  221 WILEIISwFVGGSSVLWYI-FDILNGLQGVFIF 252
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
584-852 1.66e-14

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: 74.50  E-value: 1.66e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 584 KWITYIGLSISIASLILCLIIESLFwkQTKRSQTSYTRNiclvNIAVSLLIADVWFIIAatVDPSVSPSgVCVAAVFFTH 663
Cdd:cd15991    5 KIITYTTVSLSLVALLITFILLVLI--RTLRSNLHSIHK----NLVAALFFSELIFLIG--INQTENPF-VCTVVAILLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 664 FFYLAVFFWMLVLGiLLAYRIILVFHHMAlTTMMAIGFCLGYGCPLLISiiTLAVTQPSNSYKRNDVCWLNWSDKSkpLL 743
Cdd:cd15991   76 YFYMSTFAWMFVEG-LHIYRMLTEVRNIN-TGHMRFYYVVGWGIPAIIT--GLAVGLDPQGYGNPDFCWLSVQDTL--IW 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 744 AFVVPALTIVAVNLVVVLLVLRKlwrpAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIgtMA-NSHNLAWHVLFA 822
Cdd:cd15991  150 SFAGPIGIVVIINTVIFVLAAKA----SCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGL--MAvNSDTLSFHYLFA 223
                        250       260       270
                 ....*....|....*....|....*....|
gi 341940782 823 LLNAFQGFFIFCFGILLDTKLRQLLSNKLT 852
Cdd:cd15991  224 IFSCLQGIFIFFFHCIFNKEVRKHLKNVLT 253
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
530-571 2.71e-13

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: 64.72  E-value: 2.71e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 341940782   530 PRCVFWDFSQLQWSNAGCQLVNETLDTVLCRCSHLTSFSMLM 571
Cdd:smart00303   3 PICVFWDESSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
585-833 3.41e-13

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


Pssm-ID: 320385 [Multi-domain]  Cd Length: 303  Bit Score: 71.44  E-value: 3.41e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISIASLILClIIESLFWKQTKRSQTSYTrnicLVNIAVSLLIADVWFIIA------------------ATVD 646
Cdd:cd15257    6 IISTIGCVLSIAGLVIT-IIFHLHTRKLRKSSVTWV----LLNLCSSLLLFNIIFTSGventnndyeistvpdretNTVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 647 PSVS----PSGVCVAAVFFTHFFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGFcLGYGCPLLISIITLAVT--- 719
Cdd:cd15257   81 LSEEyvepDTDVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQASA-IGWGIPAVVVAITLGATyrf 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 720 -----QPSNSYKRNDVCWLNWSDKS----KPLL-AFVVP-ALTIVAVNLVVVLLVLRKLWRpavgerlNQDDKATAIR-- 786
Cdd:cd15257  160 ptslpVFTRTYRQEEFCWLAALDKNfdikKPLLwGFLLPvGLILITNVILFIMTSQKVLKK-------NNKKLTTKKRsy 232
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 341940782 787 MGK--SLLVLTPLLGLTWGFGIGTMANSH--NLAWHVLFALLNAFQGFFIF 833
Cdd:cd15257  233 MKKiyITVSVAVVFGITWILGYLMLVNNDlsKLVFSYIFCITNTTQGVQIF 283
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
589-832 5.55e-13

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: 69.98  E-value: 5.55e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 589 IGLSISIASLILCLIIESLFWKQTKRSqtsytRNICLVNIAVSLLIADVWFIIAATvdpSVSPSGVCVAAVFFTHFFYLA 668
Cdd:cd15251   10 VGCGVSCLALLTLLAIYAAFWRYIRSE-----RSIILINFCLSIISSNILILVGQT---QTLNKGVCTMTAAFLHFFFLS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 669 VFFWMLVLgillAYRIIL-VFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQpSNSYKRNDVCWLnwSDKSKPLLAFVV 747
Cdd:cd15251   82 SFCWVLTE----AWQSYMaVTGRMRTRLIRKRFLCLGWGLPALVVAVSVGFTR-TKGYGTSSYCWL--SLEGGLLYAFVG 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 748 PALTIVAVNLVVVLLVLRKLWrpavgERLNQDDKATAIRMgkSLLVLTPLLGLTWGFGIGTMANSHNLAWHVLFALLNAF 827
Cdd:cd15251  155 PAAAVVLVNMVIGILVFNKLV-----SRDGISDNAMASLW--SSCVVLPLLALTWMSAVLAMTDRRSVLFQILFAVFDSL 227

                 ....*
gi 341940782 828 QGFFI 832
Cdd:cd15251  228 QGFVI 232
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
586-845 6.83e-13

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: 69.52  E-value: 6.83e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNIClvniaVSLLIADVWFIIAATVDPSvspSGVCVAAVFFTHFF 665
Cdd:cd15437    7 ITQLGIIISLICLSMC-IFTFWFFSEIQSTRTTIHKNLC-----CSLFLAELIFLIGINMNAN---KLFCSIIAGLLHYF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHHMALttMMAIGFCLGYGCPLLISIITLAVTQpsNSYKRNDVCWLnwSDKSKPLLAF 745
Cdd:cd15437   78 FLAAFAWMCIEGIHLYLIVVGVIYNKGF--LHKNFYIFGYGSPAVVVGISAALGY--KYYGTTKVCWL--STENNFIWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 746 VVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMANSHNLAWHvLFALLN 825
Cdd:cd15437  152 IGPACLIILVNLLAFGVIIYKVFRHTAMLKPEVSCYENIRSCARGALALLFLLGATWIFGVLHVVYGSVVTAY-LFTISN 230
                        250       260
                 ....*....|....*....|
gi 341940782 826 AFQGFFIFCFGILLDTKLRQ 845
Cdd:cd15437  231 AFQGMFIFIFLCVLSRKIQE 250
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
585-835 2.09e-12

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: 68.31  E-value: 2.09e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISIASLILCLIIESLFWKQTKrsqtSYTRNIcLVNIAVSLLIADVWFIIAATVDPSVSPSGVCVAAVFFTHF 664
Cdd:cd15444    6 FITYIGCGLSAIFLSVTLVTYIAFEKIRR----DYPSKI-LIQLCVALLLLNLVFLLDSWIALYKDIVGLCISVAVFLHY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAigFCL-GYGCPLLISIITLAVTqPSN----SYKR------NDVCWL 733
Cdd:cd15444   81 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILK--FCIvGWGVPAVVVAIVLAVS-KDNyglgSYGKspngstDDFCWI 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 734 NWSdkskplLAFVVPAL----TIVAVNLVVVLLVLRKLWRPAVGERLNQDDKaTAIRMGKSLLVLTPLLGLTWGFGIGTM 809
Cdd:cd15444  158 NNN------IVFYITVVgyfcVIFLLNISMFIVVLVQLCRIKKQKQLGAQRK-TSLQDLRSVAGITFLLGITWGFAFFAW 230
                        250       260
                 ....*....|....*....|....*.
gi 341940782 810 ANShNLAWHVLFALLNAFQGFFIFCF 835
Cdd:cd15444  231 GPV-NLAFMYLFAIFNTLQGFFIFIF 255
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
586-845 3.12e-12

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


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 67.66  E-value: 3.12e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNIClvniaVSLLIADVWFIIAatVDPSVSPSGVCVAAVFFtHFF 665
Cdd:cd16005    7 ITWVGILLSLVCLLIC-IFTFCFFRGLQSDRNTIHKNLC-----ISLFVAELLFLIG--INRTDQPIACAVFAALL-HFF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHhmALTTMMAIGFCLGYGCPLLISIITLAVTQpsNSYKRNDVCWLNWSdkSKPLLAF 745
Cdd:cd16005   78 FLAAFTWMFLEGVQLYIMLVEVFE--SEHSRRKYFYLVGYGMPALIVAVSAAVDY--RSYGTDKVCWLRLD--TYFIWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 746 VVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQ--DDKATAIRMGksLLVLTPLLGLTWGFGIgTMANSHNLAWHVLFAL 823
Cdd:cd16005  152 IGPATLIIMLNVIFLGIALYKMFHHTAILKPESgcLDNIKSWVIG--AIALLCLLGLTWAFGL-MYINESTVIMAYLFTI 228
                        250       260
                 ....*....|....*....|..
gi 341940782 824 LNAFQGFFIFCFGILLDTKLRQ 845
Cdd:cd16005  229 FNSLQGMFIFIFHCVLQKKVRK 250
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
530-570 3.70e-12

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: 61.55  E-value: 3.70e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 341940782  530 PRCVFWDFSQLQ---WSNAGCQLVNETLDTVLCRCSHLTSFSML 570
Cdd:pfam01825   1 PQCVFWDFTNSTtgrWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
586-739 1.47e-11

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: 66.09  E-value: 1.47e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFwkqtKRSQTsyTRNICLVNIAVSLLI-ADVWFIIAATVDPSVSPS-----------G 653
Cdd:cd15041    7 IYLVGYSLSLVALLPAIVIFLYF----RSLRC--TRIRLHINLFLSFILrAVFWIIWDLLVVYDRLTSsgvetvlmqnpV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 654 VCVAAVFFTHFFYLAVFFWMLVLGILLAYRIILVFHHMALTtmMAIGFCLGYGCPLLISIITLAVtqpsNSYKRNDVCWL 733
Cdd:cd15041   81 GCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSS--LKLYYAIGWGLPLVIVVIWAIV----RALLSNESCWI 154

                 ....*.
gi 341940782 734 NWSDKS 739
Cdd:cd15041  155 SYNNGH 160
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
585-835 1.80e-11

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: 65.68  E-value: 1.80e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISI----ASLILCLIIESLfwkqtkrsQTSYTRNIcLVNIAVSLLIADVWFIIAATVdPSVSPSGVCVAAVF 660
Cdd:cd15996    6 FITYIGCGISAifsaATLLTYIAFEKL--------RRDYPSKI-LMNLSTALLFLNLVFLLDGWI-ASFEIDELCITVAV 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 661 FTHFFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAigFCL-GYGCPLLISIITLAVTQPSNSY----------KRND 729
Cdd:cd15996   76 LLHFFLLATFTWMGLEAIHMYIALVKVFNTYIRRYILK--FCIiGWGLPALIVSIVLASTNDNYGYgyygkdkdgqGGDE 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 730 VCWLnwsdkSKPLLAFVVPA--------LTIVAVNLVVVLLVLRKlwrpavGERLNQDDKATAIRMGKSLLVLTPLLGLT 801
Cdd:cd15996  154 FCWI-----KNPVVFYVTCAayfgimflMNVAMFIVVMVQICGRN------GKRSNRTLREEILRNLRSVVSLTFLLGMT 222
                        250       260       270
                 ....*....|....*....|....*....|....
gi 341940782 802 WGFGIGTMAnSHNLAWHVLFALLNAFQGFFIFCF 835
Cdd:cd15996  223 WGFAFFAWG-PVNLAFMYLFTIFNSLQGLFIFVF 255
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
589-752 1.90e-11

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: 65.75  E-value: 1.90e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 589 IGLSISIASLILCLIIESLFWKQTKRSqtsytRNICLVNIAVSLLIADVWFIIAATvdpSVSPSGVCVAAVFFTHFFYLA 668
Cdd:cd15988   10 IGCAVSCMALLILLAIYAAFWRFIRSE-----RSIILLNFCLSILASNILILVGQS---QTLSKGVCTMTAAFLHFFFLS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 669 VFFWMLVlgilLAYRIIL-VFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQpSNSYKRNDVCWLnwSDKSKPLLAFVV 747
Cdd:cd15988   82 SFCWVLT----EAWQSYLaVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTR-TKGYGTASYCWL--SLEGGLLYAFVG 154

                 ....*
gi 341940782 748 PALTI 752
Cdd:cd15988  155 PAAVI 159
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
586-752 3.28e-11

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: 64.70  E-value: 3.28e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIeSLFWKQTKrsqtsYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPS-GVCVAAVFFTHF 664
Cdd:cd15263    7 IYFIGYSLSLVALSLALWI-FLYFKDLR-----CLRNTIHTNLMFTYILADLTWILTLTLQVSIGEDqKSCIILVVLLHY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGIllaYRIILVFHHMALTTM-MAIGFCLGYGCPLLIsIITLAVTQPSNSYKRNDVCWLNWSDKSKPLL 743
Cdd:cd15263   81 FHLTNFFWMFVEGL---YLYMLVVETFSGENIkLRVYAFIGWGIPAVV-IVIWAIVKALAPTAPNTALDPNGLLKHCPWM 156
                        170
                 ....*....|....*.
gi 341940782 744 A-------FVVPALTI 752
Cdd:cd15263  157 AehivdwiFQGPAILV 172
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
586-845 1.00e-10

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: 63.13  E-value: 1.00e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNICLvniavSLLIADVWFIIAAtvdPSVSPSGVCVAAVFFTHFF 665
Cdd:cd15439    7 ITYVGLIISLLCLFLA-ILTFLLCRSIRNTSTSLHLQLSL-----CLFLADLLFLVGI---DRTDNKVLCSIIAGFLHYL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILL--AYRIILVFHHMALTTMMAIGFCL-GYGCPLLISIITLAVtQPsNSYKRNDVCWLN------WS 736
Cdd:cd15439   78 FLACFAWMFLEAVHLflTVRNLKVVNYFSSHRFKKRFMYPvGYGLPAVIVAISAAV-NP-QGYGTPKHCWLSmekgfiWS 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 737 DKSkPLLAFVVPALTIVAVNlvvvllvlrkLWrpAVGERLNQDDK-ATAIRMGKSLLVLTPLLG----LTWGFGIgTMAN 811
Cdd:cd15439  156 FLG-PVCVIIVINLVLFCLT----------LW--ILREKLSSLNAeVSTLKNTRLLTFKAIAQLfilgCTWILGL-FQVG 221
                        250       260       270
                 ....*....|....*....|....*....|....
gi 341940782 812 SHNLAWHVLFALLNAFQGFFIFCFGILLDTKLRQ 845
Cdd:cd15439  222 PVATVMAYLFTITNSLQGVFIFLVHCLLNRQVRE 255
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
586-835 1.27e-10

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: 63.20  E-value: 1.27e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFWKQTKrsqtSYTRNIcLVNIAVSLLIADVWFIIAATVdPSVSPSGVCVAAVFFTHFF 665
Cdd:cd15258    7 ISYVGCGISAIFLAITILTYIAFRKLRR----DYPSKI-HMNLCAALLLLNLAFLLSSWI-ASFGSDGLCIAVAVALHYF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGFcLGYGCPLLISIITLAVtQPSNSY----------KRNDVCWLNw 735
Cdd:cd15258   81 LLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLCL-VGWGLPALLVTLVLSV-RSDNYGpitipngegfQNDSFCWIR- 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 736 sdksKPLLAFVVPALTIVAVNLVVVLLVLRKLWR-PAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMAnSHN 814
Cdd:cd15258  158 ----DPVVFYITVVGYFGLTFLFNMVMLATVLVQiCRLREKAQATPRKRALHDLLTLLGLTFLLGLTWGLAFFAWG-PFN 232
                        250       260
                 ....*....|....*....|.
gi 341940782 815 LAWHVLFALLNAFQGFFIFCF 835
Cdd:cd15258  233 LPFLYLFAIFNSLQGFFIFIW 253
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
586-851 1.70e-10

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


Pssm-ID: 320673 [Multi-domain]  Cd Length: 258  Bit Score: 62.63  E-value: 1.70e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNIClvniaVSLLIADVWFIIAatVDPSvSPSGVCVAAVFFTHFF 665
Cdd:cd16007    7 ITWVGIVISLVCLAIC-ISTFCFLRGLQTDRNTIHKNLC-----INLFLAELLFLIG--IDKT-QYQIACPIFAGLLHFF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHhmALTTMMAIGFCLGYGCPLLISIITLAVTQpsNSYKRNDVCWLNWSDKSkpLLAF 745
Cdd:cd16007   78 FLAAFSWLCLEGVQLYLMLVEVFE--SEYSRKKYYYLCGYCFPALVVGISAAIDY--RSYGTEKACWLRVDNYF--IWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 746 VVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIgTMANSHNLAWHVLFALLN 825
Cdd:cd16007  152 IGPVSFVIVVNLVFLMVTLHKMIRSSSVLKPDSSRLDNIKSWALGAITLLFLLGLTWAFGL-LFINKESVVMAYLFTTFN 230
                        250       260
                 ....*....|....*....|....*.
gi 341940782 826 AFQGFFIFCFGILLDTKLRQLLSNKL 851
Cdd:cd16007  231 AFQGMFIFIFHCALQKKVHKEYSKCL 256
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
586-845 3.75e-10

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: 61.47  E-value: 3.75e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNICLvniavSLLIADVWFIIAATVdpsVSPSGVCVAAVFFTHFF 665
Cdd:cd16006    7 ITWVGIVISLVCLAIC-IFTFCFFRGLQSDRNTIHKNLCI-----NLFIAEFIFLIGIDK---TEYKIACPIFAGLLHFF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHhmALTTMMAIGFCLGYGCPLLISIITLAVTQpsNSYKRNDVCWLNWSDKSkpLLAF 745
Cdd:cd16006   78 FLAAFAWMCLEGVQLYLMLVEVFE--SEYSRKKYYYVAGYLFPATVVGVSAAIDY--KSYGTEKACWLRVDNYF--IWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 746 VVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIgTMANSHNLAWHVLFALLN 825
Cdd:cd16006  152 IGPVTFIILLNLIFLVITLCKMVKHSNTLKPDSSRLENIKSWVLGAFALLCLLGLTWSFGL-LFINEETIVMAYLFTIFN 230
                        250       260
                 ....*....|....*....|
gi 341940782 826 AFQGFFIFCFGILLDTKLRQ 845
Cdd:cd16006  231 AFQGMFIFIFHCALQKKVRK 250
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
585-845 1.81e-09

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


Pssm-ID: 320597 [Multi-domain]  Cd Length: 262  Bit Score: 59.45  E-value: 1.81e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNIClvniaVSLLIADVWFIIAatvDPSVSPSGVCVAAVFFTHF 664
Cdd:cd15931    6 WINRVGVIVSLFCLGLA-IFTFLLCRWIPKINTTAHLHLC-----LCLSMSHTLFLAG---IEYVENELACTVMAGLLHY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGI---LLAYRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTqpSNSYKRNDVCWLNWSdkSKP 741
Cdd:cd15931   77 LFLASFVWMLLEALqlhLLVRRLTKVQVIQRDGLPRPLLCLIGYGVPFLIVGVSALVY--SDGYGEAKMCWLSQE--RGF 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 742 LLAFVVPALTIVAVNLVVVLLVLRKLwRPAVGE---RLNQDDKATAIRMgkSLLVLTPLLGLTWGFGIgTMANSHNLAWH 818
Cdd:cd15931  153 NWSFLGPVIAIIGINWILFCATLWCL-RQTLSNmnsDISQLKDTRLLTF--KAVAQLFILGCTWVLGL-FQTNPVALVFQ 228
                        250       260
                 ....*....|....*....|....*..
gi 341940782 819 VLFALLNAFQGFFIFCFGILLDTKLRQ 845
Cdd:cd15931  229 YLFTILNSLQGAFLFLVHCLLNKEVRE 255
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
586-845 2.64e-09

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


Pssm-ID: 320659 [Multi-domain]  Cd Length: 254  Bit Score: 59.09  E-value: 2.64e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFwkqtkRSQTSYTRNIcLVNIAVSLLIADVWFIIAATvdpSVSPSGVCVAAVFFTHFF 665
Cdd:cd15993    7 VTYSSVSASLAALVLTFSVLTCL-----RGLKSNTRGI-HSNIAAALFLSELLFLLGIN---RTENQFLCTVVAILLHYF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLaYRIILVFHHMALTTMMaIGFCLGYGCPLLISiiTLAVTQPSNSYKRNDVCWLNWSDKSkpLLAF 745
Cdd:cd15993   78 FLSTFAWLFVQGLHI-YRMQTEARNVNFGAMR-FYYAIGWGVPAIIT--GLAVGLDPEGYGNPDFCWISIHDKL--VWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 746 VVPALTIVAVNLVVVLLVLRKLWRPAVGERlnqdDKATAIRMGKSLLVLTPLLGLTWGFGIGTMANShNLAWHVLFALLN 825
Cdd:cd15993  152 AGPIVVVIVMNGVMFLLVARMSCSPGQKET----KKTSVLMTLRSSFLLLLLISATWLFGLLAVNNS-VLAFHYLHAILC 226
                        250       260
                 ....*....|....*....|
gi 341940782 826 AFQGFFIFCFGILLDTKLRQ 845
Cdd:cd15993  227 CLQGLAVLLLFCVLNEEVQE 246
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
586-752 3.01e-09

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


Pssm-ID: 320383 [Multi-domain]  Cd Length: 263  Bit Score: 58.71  E-value: 3.01e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIeSLFWKQTKRSQTSYTRNICLVNIAV-SLLIADVWfiiaatvdpSVSPSGVCVAAVFFTHF 664
Cdd:cd15255    7 LSFIGCGVSLCALIVTFIL-FLAVGVPKSERTTVHKNLIFALAAAeFLLMFSEW---------AKGNQVACWAVTALLHL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 665 FYLAVFFWMLVLGILLAYRIILVfhHMALTTMMAIGFCLGYGCPLLISIITLAVTqpSNSYKRNDVCWLNWsdKSKPLLA 744
Cdd:cd15255   77 FFLAAFSWMLVEGLLLWSKVVAV--NMSEDRRMKFYYVTGWGLPVVIVAVTLATS--FNKYVADQHCWLNV--QTDIIWA 150

                 ....*...
gi 341940782 745 FVVPALTI 752
Cdd:cd15255  151 FVGPVLFV 158
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
586-752 7.74e-09

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: 57.81  E-value: 7.74e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFwkqtkRSqTSYTRNICLVNIAVSLLIADV-WFIIAATVDPSVSPS--GVCVAAVFFT 662
Cdd:cd15264    7 IYYLGFSISLVALAVALIIFLYF-----RS-LRCLRNNIHCNLIVTFILRNVtWFIMQNTLTEIHHQSnqWVCRLIVTVY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 663 HFFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIgfCLGYGCPLLISIITLAVTqpsnSYKRNDVCWLNWSDKSKPL 742
Cdd:cd15264   81 NYFQVTNFFWMFVEGLYLHTMIVWAYSADKIRFWYYI--VIGWCIPCPFVLAWAIVK----LLYENEHCWLPKSENSYYD 154
                        170
                 ....*....|
gi 341940782 743 LAFVVPALTI 752
Cdd:cd15264  155 YIYQGPILLV 164
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
586-845 1.61e-08

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: 56.72  E-value: 1.61e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFwkqtKRSQTSytRNICLVNIAVSLLIADVWFIIAATvdpSVSPSGVCVAAVFFTHFF 665
Cdd:cd15436    7 ITWVGIVISLVCLLICIFTFCFF----RGLQTD--RNTIHKNLCINLFIAELLFLIGIN---RTQYTIACPIFAGLLHFF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFH-HMALTTMMAIGfclGYGCPLLISIITLAVTQpsNSYKRNDVCWLN------WSdk 738
Cdd:cd15436   78 FLAAFCWLCLEGVQLYLLLVEVFEsEYSRRKYFYLC---GYSFPALVVAVSAAIDY--RSYGTEKACWLRvdnyfiWS-- 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 739 skpllaFVVPALTIVAVNLVVVLLVLRKLWR-----PAVGERLNqDDKATAIrmgkSLLVLTPLLGLTWGFGIgTMANSH 813
Cdd:cd15436  151 ------FIGPVTFVITLNLVFLVITLHKMVShsdllKPDSSRLD-NIKSWAL----GAIALLFLLGLTWSFGL-MFINEE 218
                        250       260       270
                 ....*....|....*....|....*....|..
gi 341940782 814 NLAWHVLFALLNAFQGFFIFCFGILLDTKLRQ 845
Cdd:cd15436  219 SVVMAYLFTIFNAFQGVFIFIFHCALQKKVRK 250
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
586-732 9.22e-08

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: 54.56  E-value: 9.22e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIiesLFWKQtkRSqTSYTRNICLVNIAVSLLIADV-WFIIAATVDPSVSPSGV--CVAAVFFT 662
Cdd:cd15445    7 INYLGHCISLVALLVAFV---LFLRL--RS-IRCLRNIIHWNLITAFILRNAtWFVVQLTMSPEVHQSNVvwCRLVTAAY 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 663 HFFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIgfCLGYGCPLLIsIITLAVTQpsnSYKRNDVCW 732
Cdd:cd15445   81 NYFHVTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFI--CIGWCIPFPI-IVAWAIGK---LYYDNEKCW 144
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
586-839 9.91e-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: 54.42  E-value: 9.91e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILClIIESLFWKQTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPsGVCVAAVFFTHFF 665
Cdd:cd15442    7 ISSAGCGVSMVFLIFT-IILYFFLRFTYQKFKSEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHP-GLCKALGGVTHYF 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGI---LLAYRIILVFHHMALTTMmaigfCL-GYGCPLLISIITLAVtqpsNSY-------KRN----DV 730
Cdd:cd15442   85 LLCCFTWMAIEAFhlyLLAIKVFNTYIHHYFAKL-----CLvGWGFPALVVTITGSI----NSYgaytimdMANrttlHL 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 731 CWLNwsdkSKPLLAFVVP-----ALTIVAVNLVVVLLVLR--KLWRPAVGERLNQDDKATAIRMGKSLLVLTpllglTWG 803
Cdd:cd15442  156 CWIN----SKHLTVHYITvcgyfGLTFLFNTVVLGLVAWKifHLQSATAGKEKCQAWKGGLTVLGLSCLLGV-----TWG 226
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 341940782 804 FGIGTMANSHNLAWHvLFALLNAFQGFFIFCFGILL 839
Cdd:cd15442  227 LAFFTYGSMSVPTVY-IFALLNSLQGLFIFIWFVIL 261
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
589-832 3.74e-07

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: 52.69  E-value: 3.74e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 589 IGLSISIASLILCLIIESLFWKQTKRSqtsytRNICLVNIAVSLLIADVWFIIAATvdpSVSPSGVCVAAVFFTHFFYLA 668
Cdd:cd15990   13 VGCGVSSLTLLLLIIIYVSVWRYIRSE-----RSVILINFCLSIISSNALILIGQT---QTRNKVVCTLVAAFLHFFFLS 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 669 VFFWMLVLGillAYRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQpSNSYKRNDVCWLnwSDKSKPLLAFVVP 748
Cdd:cd15990   85 SFCWVLTEA---WQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTK-AKGYGTVNYCWL--SLEGGLLYAFVGP 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 749 ALTIVAVNLVVVLLVLRKLWrpavgERLNQDDKATAIRMGKSLLVLTPL---LGLTWGFGIGTMANSHNLAWHVLFALLN 825
Cdd:cd15990  159 AAAVVLVNMVIGILVFNKLV-----SKDGITDKKLKERAGASLWSSCVVlplLALTWMSAVLAITDRRSALFQILFAVFD 233

                 ....*..
gi 341940782 826 AFQGFFI 832
Cdd:cd15990  234 SLEGFVI 240
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
586-845 6.21e-07

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: 51.97  E-value: 6.21e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFWKQTKrsqtSYTRNIcLVNIAVSLLIADVWFIIAATVDpSVSPSGVCVAAVFFTHFF 665
Cdd:cd15997    7 ITYLGCGISSIFLGITLVTYLAFEKLRR----DYPSKI-LINLCTALLMLNLVFLLNSWLS-SFNNYGLCITVAAFLHYF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHHMALTTMMAigFCL-GYGCPLLISIITLAV-------------TQPSNSYkrndvC 731
Cdd:cd15997   81 LLASFTWMGLEAVHMYFALVKVFNIYIPNYILK--FCIaGWGIPAVVVALVLAInkdfygnelssdsLHPSTPF-----C 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 732 WL--NW----SDKSKPLLAFVVpALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAirmgksllVLTPLLGLTWGFG 805
Cdd:cd15997  154 WIqdDVvfyiSVVAYFCLIFLC-NISMFITVLIQIRSMKAKKPSRNWKQGFLHDLKSVA--------SLTFLLGLTWGFA 224
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 341940782 806 IGTMANSHNLAWHvLFALLNAFQGFFIFCFGILLDTKLRQ 845
Cdd:cd15997  225 FFAWGPVRIFFLY-LFSICNTLQGFFIFVFHCLMKENVRK 263
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
589-752 7.63e-07

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: 51.99  E-value: 7.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 589 IGLSISIASLILCLIIESLFWKQTKRSqtsytRNICLVNIAVSLLIADVWFIIAATVDPSVSpsgVCVAAVFFTHFFYLA 668
Cdd:cd15989   12 VGCGLSCLALITLAVVYAALWRYIRSE-----RSIILINFCLSIISSNILILVGQTQTHNKG---ICTMTTAFLHFFFLA 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 669 VFFWMLVlgilLAYRIILVFHHMALTTMMAIGF-CLGYGCPLLISIITLAVTQpSNSYKRNDVCWLnwSDKSKPLLAFVV 747
Cdd:cd15989   84 SFCWVLT----EAWQSYMAVTGKIRTRLIRKRFlCLGWGLPALVVAISMGFTK-AKGYGTPHYCWL--SLEGGLLYAFVG 156

                 ....*
gi 341940782 748 PALTI 752
Cdd:cd15989  157 PAAAV 161
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
584-848 1.68e-06

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: 50.59  E-value: 1.68e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 584 KWITYIGLSISIASLILCLIIESLFwKQTKRSQTSYTRNIclvniAVSLLIADVWFIIAatVDPSVSPSgVCVAAVFFTH 663
Cdd:cd15992    5 KTLTWSSVGVTLGFLLLTFLFLLCL-RALRSNKTSIRKNG-----ATALFLSELVFILG--INQADNPF-ACTVIAILLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 664 FFYLAVFFWMLVLGILLaYRIILVFHHMALTTMMaIGFCLGYGCPLLISiiTLAVTQPSNSYKRNDVCWLNWSDKSkpLL 743
Cdd:cd15992   76 FFYLCTFSWLFLEGLHI-YRMLSEVRDINYGPMR-FYYLIGWGVPAFIT--GLAVGLDPEGYGNPDFCWLSIYDTL--IW 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 744 AFVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRmgkSLLVLTPLLGLTWGFGIGTMaNSHNLAWHVLFAL 823
Cdd:cd15992  150 SFAGPVAFAVSMNVFLYILSSRASCSAQQQSFEKKKGPVSGLR---TAFTVLLLVSVTCLLALLSV-NSDVILFHYLFAG 225
                        250       260
                 ....*....|....*....|....*
gi 341940782 824 LNAFQGFFIFCFGILLDTKLRQLLS 848
Cdd:cd15992  226 FNCLQGPFIFLSHVVLLKEVRKALK 250
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
586-747 5.78e-05

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: 45.89  E-value: 5.78e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFWKqtkrsqTSYTRNICLVNI-------AVSLLIADVWFIIAATVDP----------S 648
Cdd:cd15266    7 IYTIGYSLSLISLSLALLILLLLRK------LHCTRNYIHMNLfasfilrALAVLIKDIVLYSTYSKRPddetgwisylS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 649 VSPSGVCVAAVFFTHFFYLAVFFWMLVLGILLayRIILVFHHMALTTMMAIGFCLGYGCPLLIS---IITLAVTQPSNSY 725
Cdd:cd15266   81 EESSTSCRVAQVFMHYFVGANYFWLLVEGLYL--HTLLVTAVLSERRLLKKYMLIGWGTPVLFVvpwGVAKILLENTGCW 158
                        170       180
                 ....*....|....*....|..
gi 341940782 726 KRNDVCWLNWSDKSKPLLAFVV 747
Cdd:cd15266  159 GRNENMGIWWIIRGPILLCITV 180
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
584-736 1.60e-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: 44.40  E-value: 1.60e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 584 KWITYIGLSISIASLILCLIIESLFWK-QTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPSGVCVAAVFFT 662
Cdd:cd15270    5 KIIYTVGYSISIVSLCVAVAILVAFRRlHCPRNYIHIQLFFTFILKAIAVFIKDAALFQEDDTDHCSMSTVLCKVSVVFC 84
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 341940782 663 HFFYLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIgfCLGYGCPLLISIITLAvtqpSNSYKRNDVCW-LNWS 736
Cdd:cd15270   85 HYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLV--LLGWGLPTLCTGTWIL----CKLYFEDTECWdINND 153
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
586-752 1.64e-04

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


Pssm-ID: 320388 [Multi-domain]  Cd Length: 267  Bit Score: 44.57  E-value: 1.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIIESLFwKQTKrsqtsYTRNICLVNIAVSLLIAD----VWFIIAATVDPSVSPSGV-CVAAVF 660
Cdd:cd15260    7 VYIGGYSVSLIALIISLAIFFSF-RSLR-----CTRITIHMNLFISFALNNllwiVWYKLVVDNPEVLLENPIwCQALHV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 661 FTHFFYLAVFFWMLVLGILLAYRIILVF--HHMALTTMMAIGFCLgygcPLLISIITLAVTqpSNSYKRNDVCWLNWSDK 738
Cdd:cd15260   81 LLQYFMVCNYFWMFCEGLYLHTVLVVAFisEKSLMRWFIAIGWGV----PLVITAIYAGVR--ASLPDDTERCWMEESSY 154
                        170
                 ....*....|....
gi 341940782 739 SKPLLAFVVPALTI 752
Cdd:cd15260  155 QWILIVPVVLSLLI 168
SEA pfam01390
SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed ...
153-232 3.75e-04

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: 40.68  E-value: 3.75e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782  153 GTFEI-DEKFPEDLWNSSSDVYAHYTVGIENQLKEAYRRV---HGFESVRVTQFRK--GSIVVGYEVTGSTSPPELLFAI 226
Cdd:pfam01390   5 GSFKItNLQYTPDLGNPSSQEFKSLSRRIESLLNELFRNSslrKQYIKSHVLRLRPdgGSVVVDVVLVFRFPSTEPALDR 84

                  ....*.
gi 341940782  227 EQEAEK 232
Cdd:pfam01390  85 EKLIEE 90
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
590-714 1.00e-03

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: 42.02  E-value: 1.00e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 590 GLSISIASLILCLIIESLFWKqtkrsqTSYTRNICLVNIAVS-------LLIADVWFIIAATVDPSVSPSGVCVAAVFFT 662
Cdd:cd15271   11 GYGTSLTSLITAVLIFCTFRK------LHCTRNYIHINLFVSfilralaVFIKDAVLFADESVDHCTMSTVACKAAVTFF 84
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 341940782 663 HFFYLAVFFWMLVLGILLAYRIILVFHHMalTTMMAIGFCLGYGCPLLISII 714
Cdd:cd15271   85 QFCVLANFFWLLVEGMYLQTLLLLTFTSD--RKYFWWYILIGWGAPSVTVTV 134
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
585-733 2.79e-03

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: 40.53  E-value: 2.79e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 585 WITYIGLSISIASLILCLIIeSLFWKQTKRSQTSYTRNICLVNIAVSLLIadvwfIIAATvdpSVSPSGVCVAA----VF 660
Cdd:cd15274    6 YLAIVGHSLSIATLLISLGI-FFFFRSLSCQRVTLHKNLFLSYILNSIII-----IIHLV---AVVPNGELVARnpvsCK 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 341940782 661 FTHFFYLAV----FFWMLVLGILLAYRIIL-VFhhmALTTMMAIGFCLGYGCPLLISIITlAVTQpsnSYKRNDVCWL 733
Cdd:cd15274   77 ILHFIHQYMmgcnYFWMLCEGIYLHTLIVVaVF---AEKQRLMWYYLLGWGFPLIPTTIH-AITR---AVYYNDNCWL 147
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
586-833 3.59e-03

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: 40.20  E-value: 3.59e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 586 ITYIGLSISIASLILCLIieslFWKQTKRSQTSYTRNICLvNIAVSLLIADVWFIIAATVDPSVSPSGvCVAAVFFTHFF 665
Cdd:cd15995    7 LTYVGCIISALASVFTIA----FYLCSRRKPRDYTIYVHM-NLLLAIFLLDTSFLISEPLALTGSEAA-CRAGGMFLHFS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 666 YLAVFFWMLVLGILLAYRIILVFHHMALTTMMAIGfCLGYGCPLLI------------SIITLAVTQPSNSYKRNDVCWL 733
Cdd:cd15995   81 LLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLC-AVGWGLPIFLvtliflvdqdnyGPIILAVHRSPEKVTYATICWI 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 734 nwsdkSKPLLAFVVPALTIVAVNLVVVLLVLRKLWRPAVGERLNQDDKATAIRMGKSLLVLTPLLGLTWGFGIGTMansh 813
Cdd:cd15995  160 -----TDSLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTHKWSHVLTLLGLSLVLGIPWALAFFSFASGTF---- 230
                        250       260
                 ....*....|....*....|
gi 341940782 814 NLAWHVLFALLNAFQGFFIF 833
Cdd:cd15995  231 QLVIVYLFTIINSLQGFLIF 250
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
589-736 4.56e-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: 40.04  E-value: 4.56e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 589 IGLSISIASLILCLIIESLFwKQTKRSQTSYTRNIcLVNIAVSLLIADVWFI--------IAATVDPSVSPSG------V 654
Cdd:cd15261   10 VGLCLSLVSLIISLFIFSYF-RTLRNHRTRIHKNL-FLAILLQVIIRLVLYIdqaitrsrGSHTNAATTEGRTinstpiL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 655 CVAAVFFTHFFYLAVFFWMLVLGILLayRIILVFHHMALTTMMAIGFCLGYGCPLLISIITLAVTQpsnSYKRNDVCWLN 734
Cdd:cd15261   88 CEGFYVLLEYAKTVMFMWMFIEGLYL--HNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAIVTL---IKMKVNRCWFG 162

                 ..
gi 341940782 735 WS 736
Cdd:cd15261  163 YY 164
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
589-688 4.63e-03

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: 39.84  E-value: 4.63e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341940782 589 IGLSISIASLILCLIIESLFWK-QTKRSQTSYTRNICLVNIAVSLLIADVWFIIAATVDPSVSPSGVCVAAVFFTHFFYL 667
Cdd:cd15269   10 IGHSLSLISLTAAMIILCLFRKlHCTRNYIHMHLFMSFILRAIAVFIKDAVLFESGEEDHCSVASVGCKAAMVFFQYCIM 89
                         90       100
                 ....*....|....*....|.
gi 341940782 668 AVFFWMLVLGILLAYRIILVF 688
Cdd:cd15269   90 ANFFWLLVEGLYLHTLLAVSF 110
 
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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