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Conserved domains on  [gi|568933246|ref|XP_006535803|]
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adhesion G-protein coupled receptor F3 isoform X5 [Mus musculus]

Protein Classification

hormone receptor; adhesion G protein-coupled receptor( domain architecture ID 12039915)

hormone receptor is a class B G-protein coupled receptor (GPCR) for hormones and/or hormone-related peptides; contains a large N-terminal extracellular domain that plays a critical role in peptide hormone recognition; GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins by binding to an extracellular agonist, which induces conformational changes that lead to the activation of heterotrimeric G proteins, which then bind to and activate numerous downstream effector proteins| adhesion G protein-coupled receptor such as latrophilin-3 that possesses a seven-transmembrane helix domain and a large extracellular region composed of an N-terminal lectin domain, central olfactomedin-like, hormone-binding domain, and a C-terminal GAIN domain containing a GPS motif that represents an auto-cleavage domain

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 ...
385-651 1.30e-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 cd15253:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 271  Bit Score: 398.75  E-value: 1.30e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLSQVGTGASVLALLVCLAIYGLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFL 464
Cdd:cd15253    2 FWLDFLSQVGLGASILALLLCLGIYRLVWRSVVRNKISYFRHMTLVNIAFSLLLADTCFLGATFLSAGHESPLCLAAAFL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 465 CHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQRKYLWEGKCFLNGGGVMLY 544
Cdd:cd15253   82 CHFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVTLGYLCPLLIAAATVAYYYPKRQYLHEGACWLNGESGAIY 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 545 SFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFD-GSIVSHYAFSI 623
Cdd:cd15253  162 AFSIPVLAIVLVNLLVLFVVLMKLMRPSVSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLTGeSSQVSHYGFAI 241
                        250       260
                 ....*....|....*....|....*...
gi 568933246 624 LNSLQGVFILVFGCLTDKKVLEALRKRL 651
Cdd:cd15253  242 LNAFQGVFILLFGCLMDKKVREALLKRL 269
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
329-376 3.14e-14

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.


:

Pssm-ID: 197639  Cd Length: 49  Bit Score: 67.41  E-value: 3.14e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568933246   329 GTLHCVFWDHrvfqGQGGWSDEGCEVHAANASITQCICQHLTAFSILM 376
Cdd:smart00303   1 FNPICVFWDE----SSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
49-95 1.79e-04

Hormone receptor domain; This extracellular domain contains four conserved cysteines that probably for disulphide bridges. The domain is found in a variety of hormone receptors. It may be a ligand binding domain.


:

Pssm-ID: 397086  Cd Length: 64  Bit Score: 40.05  E-value: 1.79e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568933246   49 CPEDF-SVVSWNVTKAGFVAQAPCP-----VNKKGVVKRLCGTDGIWRPVQNT 95
Cdd:pfam02793   4 CPRTWdGILCWPRTPAGETVEVPCPdyfsgFDPRGNASRNCTEDGTWSEHPPS 56
 
Name Accession Description Interval E-value
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
385-651 1.30e-134

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: 398.75  E-value: 1.30e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLSQVGTGASVLALLVCLAIYGLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFL 464
Cdd:cd15253    2 FWLDFLSQVGLGASILALLLCLGIYRLVWRSVVRNKISYFRHMTLVNIAFSLLLADTCFLGATFLSAGHESPLCLAAAFL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 465 CHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQRKYLWEGKCFLNGGGVMLY 544
Cdd:cd15253   82 CHFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVTLGYLCPLLIAAATVAYYYPKRQYLHEGACWLNGESGAIY 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 545 SFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFD-GSIVSHYAFSI 623
Cdd:cd15253  162 AFSIPVLAIVLVNLLVLFVVLMKLMRPSVSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLTGeSSQVSHYGFAI 241
                        250       260
                 ....*....|....*....|....*...
gi 568933246 624 LNSLQGVFILVFGCLTDKKVLEALRKRL 651
Cdd:cd15253  242 LNAFQGVFILLFGCLMDKKVREALLKRL 269
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
386-632 2.43e-29

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: 116.99  E-value: 2.43e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246  386 TLDLLSQVGTGASVLALLVCLAIYGLVWRVVVrnkvafFRHTTLFNMVICLLVADTCFL------GSPFLPSGYHSLICL 459
Cdd:pfam00002   3 SLKVIYTVGYSLSLVALLLAIAIFLLFRKLHC------TRNYIHLNLFASFILRALLFLvgdavlFNKQDLDHCSWVGCK 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246  460 VTAFLCHFFYLATFFWMLAQALVLAHQLLFVFhqLSKHVVLSLMVMLGYLCPLGFAGVTLGLYlpQRKYLWEGKCFLNGG 539
Cdd:pfam00002  77 VVAVFLHYFFLANFFWMLVEGLYLYTLLVEVF--FSERKYFWWYLLIGWGVPALVVGIWAGVD--PKGYGEDDGCWLSNE 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246  540 GVMLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVS-- 617
Cdd:pfam00002 153 NGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFAFNPENTLRvv 232
                         250
                  ....*....|....*.
gi 568933246  618 -HYAFSILNSLQGVFI 632
Cdd:pfam00002 233 fLYLFLILNSFQGFFV 248
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
329-376 3.14e-14

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.


Pssm-ID: 197639  Cd Length: 49  Bit Score: 67.41  E-value: 3.14e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568933246   329 GTLHCVFWDHrvfqGQGGWSDEGCEVHAANASITQCICQHLTAFSILM 376
Cdd:smart00303   1 FNPICVFWDE----SSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
332-375 1.00e-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: 62.71  E-value: 1.00e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568933246  332 HCVFWDHRVFqGQGGWSDEGCEVHAANASITQCICQHLTAFSIL 375
Cdd:pfam01825   2 QCVFWDFTNS-TTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
49-95 1.79e-04

Hormone receptor domain; This extracellular domain contains four conserved cysteines that probably for disulphide bridges. The domain is found in a variety of hormone receptors. It may be a ligand binding domain.


Pssm-ID: 397086  Cd Length: 64  Bit Score: 40.05  E-value: 1.79e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568933246   49 CPEDF-SVVSWNVTKAGFVAQAPCP-----VNKKGVVKRLCGTDGIWRPVQNT 95
Cdd:pfam02793   4 CPRTWdGILCWPRTPAGETVEVPCPdyfsgFDPRGNASRNCTEDGTWSEHPPS 56
HormR smart00008
Domain present in hormone receptors;
49-91 3.83e-04

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 39.42  E-value: 3.83e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568933246    49 CPEDF-SVVSWNVTKAGFVAQAPCP-----VNKKGVVKRLCGTDGIWRP 91
Cdd:smart00008   5 CPATWdGIICWPQTPAGQLVEVPCPkyfsgFSYKTGASRNCTENGGWSP 53
 
Name Accession Description Interval E-value
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
385-651 1.30e-134

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: 398.75  E-value: 1.30e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLSQVGTGASVLALLVCLAIYGLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFL 464
Cdd:cd15253    2 FWLDFLSQVGLGASILALLLCLGIYRLVWRSVVRNKISYFRHMTLVNIAFSLLLADTCFLGATFLSAGHESPLCLAAAFL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 465 CHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQRKYLWEGKCFLNGGGVMLY 544
Cdd:cd15253   82 CHFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVTLGYLCPLLIAAATVAYYYPKRQYLHEGACWLNGESGAIY 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 545 SFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFD-GSIVSHYAFSI 623
Cdd:cd15253  162 AFSIPVLAIVLVNLLVLFVVLMKLMRPSVSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLTGeSSQVSHYGFAI 241
                        250       260
                 ....*....|....*....|....*...
gi 568933246 624 LNSLQGVFILVFGCLTDKKVLEALRKRL 651
Cdd:cd15253  242 LNAFQGVFILLFGCLMDKKVREALLKRL 269
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
384-648 8.42e-112

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: 340.06  E-value: 8.42e-112
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 384 NPTLDLLSQVGTGASVLALLVCLAIYGLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSPFL-PSGYHSLICLVTA 462
Cdd:cd15932    1 SPALDYITYVGLGISILSLVLCLIIEALVWKSVTKNKTSYMRHVCLVNIALSLLIADIWFIIGAAIsTPPNPSPACTAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 463 FLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQRKYLWEGKCFLNGGGVM 542
Cdd:cd15932   81 FFIHFFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITVAATAPQGGYTRKGVCWLNWDKTK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 543 -LYSFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDG-SIVSHYA 620
Cdd:cd15932  161 aLLAFVIPALAIVVVNFIILIVVIFKLLRPSVGERPSKDEKNALVQIGKSVAILTPLLGLTWGFGLGTMIDPkSLAFHII 240
                        250       260
                 ....*....|....*....|....*...
gi 568933246 621 FSILNSLQGVFILVFGCLTDKKVLEALR 648
Cdd:cd15932  241 FAILNSFQGFFILVFGTLLDSKVREALL 268
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
386-650 5.00e-69

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: 228.15  E-value: 5.00e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSGYHSL---ICLVTA 462
Cdd:cd15254    3 ELDYITYIGLSISILSLAICIVIESLVWKSVTKNRTSYMRHVCILNIAVSLLIADIWFIVVAAIQDQNYAVngnVCVAAT 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 463 FLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQRKYLWEGKCFLN-GGGV 541
Cdd:cd15254   83 FFIHFFYLCVFFWMLALGLMLFYRLVFILHDTSKTIQKAVAFCLGYGCPLIISVITIAVTLPRDSYTRKKVCWLNwEDSK 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 542 MLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGS-IVSHYA 620
Cdd:cd15254  163 ALLAFVIPALIIVAVNSIITVVVIVKILRPSIGEKPSKQERSSLFQIIKSIGVLTPLLGLTWGFGLATVIKGSsIVFHIL 242
                        250       260       270
                 ....*....|....*....|....*....|
gi 568933246 621 FSILNSLQGVFILVFGCLTDKKVLEALRKR 650
Cdd:cd15254  243 FTLLNAFQGLFILVFGTLWDKKVQEALLNK 272
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
384-648 9.03e-56

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: 191.98  E-value: 9.03e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 384 NPTLDLLSQVGTGASVLALLVCLAIYGLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCF-LGSPFLPSGYHSLICLVTA 462
Cdd:cd15994    1 NAVLDYITRIGLGLSIFSLALCLTIEAVVWSHVTKTEITYMRHVCIVNIATSLLIADVWFiLASIVHNTALNYPLCVAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 463 FLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQRKYLWEGKCFLNGGGV- 541
Cdd:cd15994   81 FFLHFFYLSLFFWMLTKALLILYGILLVFFKITKSVFIATAFSIGYGCPLVIAVLTVAITEPKKGYLRPEACWLNWDETk 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 542 MLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRqALVGVLKALLILTPIFGLTWGLGVATLFDG-SIVSHYA 620
Cdd:cd15994  161 ALLAFIIPALSIVVVNLIVVGVVVVKTQRSSIGESCKQDVS-NIIRISKNVAILTPLLGLTWGFGLATIIDSrSLPFHII 239
                        250       260
                 ....*....|....*....|....*...
gi 568933246 621 FSILNSLQGVFILVFGCLTDKKVLEALR 648
Cdd:cd15994  240 FALLNAFQGFFILLFGTILDRKIRIALY 267
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
386-646 1.70e-53

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


Pssm-ID: 320168 [Multi-domain]  Cd Length: 253  Bit Score: 185.47  E-value: 1.70e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVWRVVVRnkvafFRHTTLFNMVICLLVADTCFLGSPFLPSgyHSLICLVTAFLC 465
Cdd:cd15040    3 ALSIITYIGCGLSLLGLLLTIITYILFRKLRKR-----KPTKILLNLCLALLLANLLFLFGINSTD--NPVLCTAVAALL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 466 HFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLsLMVMLGYLCPLGFAGVTLGLYlPQRKYLWEGKCFLNGGGVMLYS 545
Cdd:cd15040   76 HYFLLASFMWMLVEALLLYLRLVKVFGTYPRHFIL-KYALIGWGLPLIIVIITLAVD-PDSYGNSSGYCWLSNGNGLYYA 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 546 FSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPtvEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILN 625
Cdd:cd15040  154 FLGPVLLIILVNLVIFVLVLRKLLRLSAKRNK--KKRKKTKAQLRAAVSLFFLLGLTWIFGILAIFGARVVFQYLFAIFN 231
                        250       260
                 ....*....|....*....|.
gi 568933246 626 SLQGVFILVFGCLTDKKVLEA 646
Cdd:cd15040  232 SLQGFFIFIFHCLRNKEVRKA 252
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
385-647 4.46e-49

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


Pssm-ID: 410627 [Multi-domain]  Cd Length: 260  Bit Score: 173.55  E-value: 4.46e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLSQVGTGASVLALLVCLAIYGLVWRVvvRNkvafFRHTTLFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFL 464
Cdd:cd13952    2 LALSIITYIGCSLSLVGLLLTIITYLLFPKL--RN----LRGKILINLCLSLLLAQLLFLIGQLLTSSDRPVLCKALAIL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 465 CHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLsLMVMLGYLCPLGFAGVTLGL---YLPQRKYLWEGKCFLNGGGV 541
Cdd:cd13952   76 LHYFLLASFFWMLVEAFDLYRTFVKVFGSSERRRFL-KYSLYGWGLPLLIVIITAIVdfsLYGPSPGYGGEYCWLSNGNA 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 542 MLYSFSEPVLAIVGVNGLVLVIAVLKLLRpSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLG-VATLFDGSIVSHYA 620
Cdd:cd13952  155 LLWAFYGPVLLILLVNLVFFILTVRILLR-KLRETPKQSERKSDRKQLRAYLKLFPLMGLTWIFGiLAPFVGGSLVFWYL 233
                        250       260
                 ....*....|....*....|....*..
gi 568933246 621 FSILNSLQGVFILVFGCLTDKKVLEAL 647
Cdd:cd13952  234 FDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
387-647 2.63e-37

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: 140.16  E-value: 2.63e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYgLVWRVVVRNKvaFFRHTtlfNMVICLLVADTCFLGSPFLPSgyHSLICLVTAFLCH 466
Cdd:cd15933    4 LSIISYIGCGISIACLALTLIIF-LVLRVLSSDR--FQIHK---NLCVALLLAQILLLAGEWAEG--NKVACKVVAILLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 467 FFYLATFFWMLAQALVLAHQLLFVFHQLSKHvvlSLMVMLGYLCPLGFAGVTLGlYLPQrKYLWEGKCFLNGGGVMLYSF 546
Cdd:cd15933   76 FFFMAAFSWMLVEGLHLYLMIVKVFNYKSKM---RYYYFIGWGLPAIIVAISLA-ILFD-DYGSPNVCWLSLDDGLIWAF 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 547 SEPVLAIVGVNGLVLvIAVLKL--LRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSIL 624
Cdd:cd15933  151 VGPVIFIITVNTVIL-ILVVKItvSLSTNDAKKSQGTLAQIKSTAKASVVLLPILGLTWLFGVLVVNSQTIVFQYIFVIL 229
                        250       260
                 ....*....|....*....|...
gi 568933246 625 NSLQGVFILVFGCLTDKKVLEAL 647
Cdd:cd15933  230 NSLQGLMIFLFHCVLNSEVRSAF 252
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
386-652 4.22e-34

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


Pssm-ID: 320556 [Multi-domain]  Cd Length: 259  Bit Score: 131.23  E-value: 4.22e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYglvwrVVVRNkVAFFRHTTLFNMVICLLVADTCFLGSPFLPSgyHSLICLVTAFLC 465
Cdd:cd15440    3 ALTFITYIGCIISIVCLLLAFITF-----TCFRN-LQCDRNTIHKNLCLCLLIAEIVFLLGIDQTE--NRTLCGVIAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 466 HFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVmlGYLCPLGFAGVTLGLYLpqRKYLWEGKCFLNGGGVMLYS 545
Cdd:cd15440   75 HYFFLAAFSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLF--GYGLPALIVAVSAGVDP--TGYGTEDHCWLSTENGFIWS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 546 FSEPVLAIVGVNGLVLVIAVLKLLR--PSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSI 623
Cdd:cd15440  151 FVGPVIVVLLANLVFLGMAIYVMCRhsSRSASKKDASKLKNIRGWLKGSIVLVVLLGLTWTFGLLFINQESIVMAYIFTI 230
                        250       260
                 ....*....|....*....|....*....
gi 568933246 624 LNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15440  231 LNSLQGLFIFIFHCVLNEKVRKELRRWLR 259
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
386-632 2.43e-29

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: 116.99  E-value: 2.43e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246  386 TLDLLSQVGTGASVLALLVCLAIYGLVWRVVVrnkvafFRHTTLFNMVICLLVADTCFL------GSPFLPSGYHSLICL 459
Cdd:pfam00002   3 SLKVIYTVGYSLSLVALLLAIAIFLLFRKLHC------TRNYIHLNLFASFILRALLFLvgdavlFNKQDLDHCSWVGCK 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246  460 VTAFLCHFFYLATFFWMLAQALVLAHQLLFVFhqLSKHVVLSLMVMLGYLCPLGFAGVTLGLYlpQRKYLWEGKCFLNGG 539
Cdd:pfam00002  77 VVAVFLHYFFLANFFWMLVEGLYLYTLLVEVF--FSERKYFWWYLLIGWGVPALVVGIWAGVD--PKGYGEDDGCWLSNE 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246  540 GVMLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVS-- 617
Cdd:pfam00002 153 NGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFAFNPENTLRvv 232
                         250
                  ....*....|....*.
gi 568933246  618 -HYAFSILNSLQGVFI 632
Cdd:pfam00002 233 fLYLFLILNSFQGFFV 248
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
386-653 9.00e-28

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: 112.73  E-value: 9.00e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVwrvvvrNKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSgyHSLICLVTAFLC 465
Cdd:cd15441    3 LLKIVTYIGIGISLVLLVIAFLVLSCL------RGLQSNSNSIHKNLVACLLLAELLFLLGINQTE--NLFPCKLIAILL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 466 HFFYLATFFWMLAQALVLAHQLLFVfhQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQrkYLWEGKCFLNGGGVMLYS 545
Cdd:cd15441   75 HYFYLSAFSWLLVESLHLYRMLTEP--RDINHGHMRFYYLLGYGIPAIIVGLSVGLRPDG--YGNPDFCWLSVNETLIWS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 546 FSEPVLAIVGVNGLVLVIAvlklLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILN 625
Cdd:cd15441  151 FAGPIAFVIVITLIIFILA----LRASCTLKRHVLEKASVRTDLRSSFLLLPLLGATWVFGLLAVNEDSELLHYLFAGLN 226
                        250       260
                 ....*....|....*....|....*...
gi 568933246 626 SLQGVFILVFGCLTDKKVLEALRKRLRG 653
Cdd:cd15441  227 FLQGLFIFLFYCIFNKKVRRELKNALLR 254
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
387-652 2.77e-27

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


Pssm-ID: 320380 [Multi-domain]  Cd Length: 257  Bit Score: 111.44  E-value: 2.77e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYGLVwrvvvrNKVAFFRHTTLFNMVICLLVADTCFLGSpfLPSGYHSLICLVTAFLCH 466
Cdd:cd15252    4 LTRITQVGIIISLVCLAICIFTFWFF------RGLQSDRTTIHKNLCISLFLAELVFLIG--INTTTNKIFCSVIAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 467 FFYLATFFWMLAQALVLAHQLLFVFHqlSKHVVLSLMVMLGYLCPLGFAGVTLGLYlpQRKYLWEGKCFLNGGGVMLYSF 546
Cdd:cd15252   76 YFFLAAFAWMFIEGIQLYLMLVEVFE--NEGSRHKNFYIFGYGSPAVIVGVSAALG--YRYYGTTKVCWLSTENYFIWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 547 SEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILNS 626
Cdd:cd15252  152 IGPATLIILLNLIFLGVAIYKMFRHTAGLKPEVSCLENIRSWARGAIALLFLLGLTWIFGVLHINHASVVMAYLFTVSNS 231
                        250       260
                 ....*....|....*....|....*.
gi 568933246 627 LQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15252  232 LQGMFIFLFHCVLSRKVRKEYYKLFR 257
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
386-649 7.43e-27

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: 110.24  E-value: 7.43e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVwrvvvrNKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSGyhSLICLVTAFLC 465
Cdd:cd15438    3 PLTLITKVGLSVSLFCLFLCILTFLFC------RSIRGTRNTIHLHLCLSLFLAHLIFLLGINNTNN--QVACAVVAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 466 HFFYLATFFWMLAQALVLAHQLLFVFHqlSKHVVLSLMVMLGYLCPLGFAGVTLGLYlpQRKYLWEGKCFLNGGGVMLYS 545
Cdd:cd15438   75 HYFFLAAFCWMSLEGVELYLMVVQVFN--TQSLKKRYLLLIGYGVPLVIVAISAAVN--SKGYGTQRHCWLSLERGFLWS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 546 FSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEK-RQALVGVLKALLILTpIFGLTWGLGVATLFDGSIVSHYAFSIL 624
Cdd:cd15438  151 FLGPVCLIILVNAIIFVITVWKLAEKFSSINPDMEKlRKIRALTITAIAQLC-ILGCTWIFGFFQFSDSTLVMSYLFTIL 229
                        250       260
                 ....*....|....*....|....*
gi 568933246 625 NSLQGVFILVFGCLTDKKVLEALRK 649
Cdd:cd15438  230 NSLQGLFIFLLHCLLSKQVREEYSR 254
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
385-653 4.64e-26

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: 108.20  E-value: 4.64e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLSQVGTGASVLALLVCLAIYgLVWRVVvRNKvaffrHTTL-FNMVICLLVADTCFLGSpfLPSGYHSLICLVTAF 463
Cdd:cd15439    2 LALTVITYVGLIISLLCLFLAILTF-LLCRSI-RNT-----STSLhLQLSLCLFLADLLFLVG--IDRTDNKVLCSIIAG 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 464 LCHFFYLATFFWMLAQALVLAHQL--LFVFHQLSKHVVlslmvMLGYLCPLGF----------AGVTLGLYLPQRKylwe 531
Cdd:cd15439   73 FLHYLFLACFAWMFLEAVHLFLTVrnLKVVNYFSSHRF-----KKRFMYPVGYglpavivaisAAVNPQGYGTPKH---- 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 532 gkCFLNGGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLS----EGPTVEKRQALVgvLKALLILTpIFGLTWGLGV 607
Cdd:cd15439  144 --CWLSMEKGFIWSFLGPVCVIIVIN-LVLFCLTLWILREKLSslnaEVSTLKNTRLLT--FKAIAQLF-ILGCTWILGL 217
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 568933246 608 ATLFDGSIVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLRG 653
Cdd:cd15439  218 FQVGPVATVMAYLFTITNSLQGVFIFLVHCLLNRQVREEYRRWITG 263
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
385-652 4.20e-25

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: 105.39  E-value: 4.20e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLSQVGTGASVLALLVCLAIYGLVWRVvvRN---KvaffrhtTLFNMVICLLVADTCFLGSPFLPSGYHSLiCLVT 461
Cdd:cd15039    2 SILGILTLIGLIISLVFLLLTLAVYALLPEL--RNlhgK-------CLMCLVLSLFVAYLLLLIGQLLSSGDSTL-CVAL 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 462 AFLCHFFYLATFFWMlaqaLVLAHQLLFVFHQLSKHVVLS-------LMVMLGYLCPLGFAGVTLGLYL-----PQRKYL 529
Cdd:cd15039   72 GILLHFFFLAAFFWL----NVMSFDIWRTFRGKRSSSSRSkerkrflRYSLYAWGVPLLLVAVTIIVDFspntdSLRPGY 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 530 WEGKCFLNGGGVMLYSFSEPVLAIVGVNGLVLVIAVLKLLRpslsegptVEKRQALVGV--------LKALLILTPIFGL 601
Cdd:cd15039  148 GEGSCWISNPWALLLYFYGPVALLLLFNIILFILTAIRIRK--------VKKETAKVQSrlrsdkqrFRLYLKLFVIMGV 219
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568933246 602 TWGLG-VATLFDGSIVSHYAFSILNSLQGVFI-LVFGCLtdKKVLEALRKRLR 652
Cdd:cd15039  220 TWILEiISWFVGGSSVLWYIFDILNGLQGVFIfLIFVCK--RRVLRLLKKKIR 270
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
388-652 9.52e-25

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: 104.23  E-value: 9.52e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 388 DLLSQVGTGASVLALLVCLAIygLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSpfLPSGYHSLICLVTAFLCHF 467
Cdd:cd16006    1 ELLLTVITWVGIVISLVCLAI--CIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIG--IDKTEYKIACPIFAGLLHF 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 468 FYLATFFWMLAQALVLAHQLLFVFHqlSKHVVLSLMVMLGYLCPLGFAGVTLGLylPQRKYLWEGKCFLNGGGVMLYSFS 547
Cdd:cd16006   77 FFLAAFAWMCLEGVQLYLMLVEVFE--SEYSRKKYYYVAGYLFPATVVGVSAAI--DYKSYGTEKACWLRVDNYFIWSFI 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 548 EPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILNSL 627
Cdd:cd16006  153 GPVTFIILLNLIFLVITLCKMVKHSNTLKPDSSRLENIKSWVLGAFALLCLLGLTWSFGLLFINEETIVMAYLFTIFNAF 232
                        250       260
                 ....*....|....*....|....*
gi 568933246 628 QGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd16006  233 QGMFIFIFHCALQKKVRKEYSKCFR 257
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
384-649 7.50e-24

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: 101.82  E-value: 7.50e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 384 NPTLDLLSQVGTGASVLALLVCLAIYGLVwrvvvrNKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSGyhSLICLVTAF 463
Cdd:cd15931    1 DPFLEWINRVGVIVSLFCLGLAIFTFLLC------RWIPKINTTAHLHLCLCLSMSHTLFLAGIEYVEN--ELACTVMAG 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 464 LCHFFYLATFFWMLAQALVL---AHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYlpQRKYLWEGKCFLNGGG 540
Cdd:cd15931   73 LLHYLFLASFVWMLLEALQLhllVRRLTKVQVIQRDGLPRPLLCLIGYGVPFLIVGVSALVY--SDGYGEAKMCWLSQER 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 541 VMLYSFSEPVLAIVGVNGLVLViAVLKLLRPSLSE-GPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHY 619
Cdd:cd15931  151 GFNWSFLGPVIAIIGINWILFC-ATLWCLRQTLSNmNSDISQLKDTRLLTFKAVAQLFILGCTWVLGLFQTNPVALVFQY 229
                        250       260       270
                 ....*....|....*....|....*....|
gi 568933246 620 AFSILNSLQGVFILVFGCLTDKKVLEALRK 649
Cdd:cd15931  230 LFTILNSLQGAFLFLVHCLLNKEVREEYIK 259
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
388-652 9.94e-23

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: 98.46  E-value: 9.94e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 388 DLLSQVGTGASVLALLVCLAIygLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSpfLPSGYHSLICLVTAFLCHF 467
Cdd:cd16007    1 ELLLSVITWVGIVISLVCLAI--CISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLIG--IDKTQYQIACPIFAGLLHF 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 468 FYLATFFWMLAQALVLAHQLLFVFHqlSKHVVLSLMVMLGYLCPLGFAGVTLGLylPQRKYLWEGKCFLNGGGVMLYSFS 547
Cdd:cd16007   77 FFLAAFSWLCLEGVQLYLMLVEVFE--SEYSRKKYYYLCGYCFPALVVGISAAI--DYRSYGTEKACWLRVDNYFIWSFI 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 548 EPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILNSL 627
Cdd:cd16007  153 GPVSFVIVVNLVFLMVTLHKMIRSSSVLKPDSSRLDNIKSWALGAITLLFLLGLTWAFGLLFINKESVVMAYLFTTFNAF 232
                        250       260
                 ....*....|....*....|....*
gi 568933246 628 QGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd16007  233 QGMFIFIFHCALQKKVHKEYSKCLR 257
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
387-652 1.12e-21

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: 95.38  E-value: 1.12e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYGLVWRV-VVRNKvaffRHTTLFNMVICLLVADTCFLGSPFLPSGyhSLICLVTAFLC 465
Cdd:cd15256    4 LSSITYVGCSLSIFCLAITLVTFAVLSSVsTIRNQ----RYHIHANLSFAVLVAQILLLISFRFEPG--TLPCKIMAILL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 466 HFFYLATFFWMLAQALVLAHQLLFVF-HQLSKHVVLSLMvmlGYLCPLGFAGVTLGLYLpqRKYLWEGKCFLNGGGVMLY 544
Cdd:cd15256   78 HFFFLSAFAWMLVEGLHLYSMVIKVFgSEESKHFYYYGI---GWGSPLLICIISLTSAL--DSYGESDNCWLSLENGAIW 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 545 SFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEK-RQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSI 623
Cdd:cd15256  153 AFVAPALFVIVVN-IGILIAVTRVISRISADNYKVHGdANAFKLTAKAVAVLLPILGSSWVFGVLAVNTHALVFQYMFAI 231
                        250       260
                 ....*....|....*....|....*....
gi 568933246 624 LNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15256  232 FNSLQGFFIFLFHCLLNSEVRAAFKHKTK 260
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
387-652 2.36e-20

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: 91.54  E-value: 2.36e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYGLVwrvvvrNKVAFFRHTTLFNMVICLLVADTCFLGSpfLPSGYHSLICLVTAFLCH 466
Cdd:cd16005    4 LDVITWVGILLSLVCLLICIFTFCFF------RGLQSDRNTIHKNLCISLFVAELLFLIG--INRTDQPIACAVFAALLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 467 FFYLATFFWMLAQALVLAHQLLFVFHqlSKHVVLSLMVMLGYLCPLGFAGVTLGLylPQRKYLWEGKCFLNGGGVMLYSF 546
Cdd:cd16005   76 FFFLAAFTWMFLEGVQLYIMLVEVFE--SEHSRRKYFYLVGYGMPALIVAVSAAV--DYRSYGTDKVCWLRLDTYFIWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 547 SEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILNS 626
Cdd:cd16005  152 IGPATLIIMLNVIFLGIALYKMFHHTAILKPESGCLDNIKSWVIGAIALLCLLGLTWAFGLMYINESTVIMAYLFTIFNS 231
                        250       260
                 ....*....|....*....|....*.
gi 568933246 627 LQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd16005  232 LQGMFIFIFHCVLQKKVRKEYGKCLR 257
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
388-652 2.57e-19

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


Pssm-ID: 320552 [Multi-domain]  Cd Length: 258  Bit Score: 88.31  E-value: 2.57e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 388 DLLSQVGTGASVLALLVCLAIygLVWRVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSpfLPSGYHSLICLVTAFLCHF 467
Cdd:cd15436    1 ELLLFVITWVGIVISLVCLLI--CIFTFCFFRGLQTDRNTIHKNLCINLFIAELLFLIG--INRTQYTIACPIFAGLLHF 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 468 FYLATFFWMLAQALVLAHQLLFVFHqlSKHVVLSLMVMLGYLCPLGFAGVTLGLylPQRKYLWEGKCFLNGGGVMLYSFS 547
Cdd:cd15436   77 FFLAAFCWLCLEGVQLYLLLVEVFE--SEYSRRKYFYLCGYSFPALVVAVSAAI--DYRSYGTEKACWLRVDNYFIWSFI 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 548 EPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILNSL 627
Cdd:cd15436  153 GPVTFVITLNLVFLVITLHKMVSHSDLLKPDSSRLDNIKSWALGAIALLFLLGLTWSFGLMFINEESVVMAYLFTIFNAF 232
                        250       260
                 ....*....|....*....|....*
gi 568933246 628 QGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15436  233 QGVFIFIFHCALQKKVRKEYSKCLR 257
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
386-649 5.15e-18

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: 84.52  E-value: 5.15e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVwrvvvrnKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFLc 465
Cdd:cd15255    3 TLRTLSFIGCGVSLCALIVTFILFLAV-------GVPKSERTTVHKNLIFALAAAEFLLMFSEWAKGNQVACWAVTALL- 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 466 HFFYLATFFWMLAQALVLAHQLLFVfhQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLpqRKYLWEGKCFLNGGGVMLYS 545
Cdd:cd15255   75 HLFFLAAFSWMLVEGLLLWSKVVAV--NMSEDRRMKFYYVTGWGLPVVIVAVTLATSF--NKYVADQHCWLNVQTDIIWA 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 546 FSEPVLAIVGVNGLVLVIAVL----------KLLRPSlsegPTVEKRQALV--GVLKALLILTPIFGLTWGLGVatLFDG 613
Cdd:cd15255  151 FVGPVLFVLTVNTFVLFRVVMvtvssarrraKMLTPS----SDLEKQIGIQiwATAKPVLVLLPVLGLTWLCGV--LVHL 224
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 568933246 614 SIVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRK 649
Cdd:cd15255  225 SDVWAYVFITLNSFQGLYIFLVYAIYNSEVRNAIQR 260
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
387-645 5.80e-18

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: 84.54  E-value: 5.80e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYGLVwrvvvrNKVAFFRHTTLFNMVICLLVADTCFLGSpfLPSGYHSLICLVTAFLCH 466
Cdd:cd15437    4 LTRITQLGIIISLICLSMCIFTFWFF------SEIQSTRTTIHKNLCCSLFLAELIFLIG--INMNANKLFCSIIAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 467 FFYLATFFWMLAQALVL-------------AHQLLFVFHQLSKHVVLSLMVMLGYlcplgfagvtlglylpqRKYLWEGK 533
Cdd:cd15437   76 YFFLAAFAWMCIEGIHLylivvgviynkgfLHKNFYIFGYGSPAVVVGISAALGY-----------------KYYGTTKV 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 534 CFLNGGGVMLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDG 613
Cdd:cd15437  139 CWLSTENNFIWSFIGPACLIILVNLLAFGVIIYKVFRHTAMLKPEVSCYENIRSCARGALALLFLLGATWIFGVLHVVYG 218
                        250       260       270
                 ....*....|....*....|....*....|..
gi 568933246 614 SIVSHYAFSILNSLQGVFILVFGCLTDKKVLE 645
Cdd:cd15437  219 SVVTAYLFTISNAFQGMFIFIFLCVLSRKIQE 250
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
385-652 1.19e-17

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: 83.46  E-value: 1.19e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLsqVGTGASVLALLVCLAIYGLVWRVVVRNkvaffRHTTLFNMVICLLVADTCFLGSPflPSGYHSLICLVTAFL 464
Cdd:cd15251    4 PSVTLI--VGCGVSCLALLTLLAIYAAFWRYIRSE-----RSIILINFCLSIISSNILILVGQ--TQTLNKGVCTMTAAF 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 465 CHFFYLATFFWMLAQALvlaHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGlYLPQRKYLWEGKCFLNGGGVMLY 544
Cdd:cd15251   75 LHFFFLSSFCWVLTEAW---QSYMAVTGRMRTRLIRKRFLCLGWGLPALVVAVSVG-FTRTKGYGTSSYCWLSLEGGLLY 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 545 SFSEPVLAIVGVNGLVLVIAVLKLL-RPSLSEgptvekrQALVGVLKALLILtPIFGLTWGLGVATLFDG-SIVSHYAFS 622
Cdd:cd15251  151 AFVGPAAAVVLVNMVIGILVFNKLVsRDGISD-------NAMASLWSSCVVL-PLLALTWMSAVLAMTDRrSVLFQILFA 222
                        250       260       270
                 ....*....|....*....|....*....|
gi 568933246 623 ILNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15251  223 VFDSLQGFVIVMVHCILRREVQDAVKCRMG 252
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
389-652 1.62e-17

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


Pssm-ID: 341321 [Multi-domain]  Cd Length: 273  Bit Score: 83.43  E-value: 1.62e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 389 LLSQVGTGASVLALLVCLAIYGLVWRV-VVRNKVaffrHTTLFNMVIC----------LLVADTCFLGSPFLPSGYHSLI 457
Cdd:cd15041    6 YIYLVGYSLSLVALLPAIVIFLYFRSLrCTRIRL----HINLFLSFILravfwiiwdlLVVYDRLTSSGVETVLMQNPVG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 458 CLVTAFLCHFFYLATFFWMLAQALVLaHQLLFV--FHQLSKhvvLSLMVMLGYlcplGFAGVTLGLYLPQRKYLWEGKCF 535
Cdd:cd15041   82 CKLLSVLKRYFKSANYFWMLCEGLYL-HRLIVVafFSEPSS---LKLYYAIGW----GLPLVIVVIWAIVRALLSNESCW 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 536 L-NGGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQALVGVlKALLILTPIFGLTWGL---GVATLF 611
Cdd:cd15041  154 IsYNNGHYEWILYGPNLLALLVN-LFFLINILRILLTKLRSHPNAEPSNYRKAV-KATLILIPLFGIQYLLtiyRPPDGS 231
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 568933246 612 DGSIVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15041  232 EGELVYEYFNAILNSSQGFFVAVIYCFLNGEVQSELKRKWS 272
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
382-653 6.21e-17

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: 81.92  E-value: 6.21e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 382 PENPTLDLLsqVGTGASVLALLVCLAIYGLVWRVVVRNkvaffRHTTLFNMVICLLVADTCFL--GSPFLPSGyhslICL 459
Cdd:cd15988    1 TGSPSVPLM--IGCAVSCMALLILLAIYAAFWRFIRSE-----RSIILLNFCLSILASNILILvgQSQTLSKG----VCT 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 460 VTAFLCHFFYLATFFWMLAQALvlaHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGlYLPQRKYLWEGKCFLNGG 539
Cdd:cd15988   70 MTAAFLHFFFLSSFCWVLTEAW---QSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVG-FTRTKGYGTASYCWLSLE 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 540 GVMLYSFSEPVLAIVGVNGLVLVIAVLKLL-RPSLSE--------GPTVEKRQALV-----GVLKALL------------ 593
Cdd:cd15988  146 GGLLYAFVGPAAVIVLVNMLIGIIVFNKLMsRDGISDkskkqragSEAEPCSSLLLkcskcGVVSSAAmssatassamas 225
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568933246 594 -----ILTPIFGLTWGLGVATLFD-GSIVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLRG 653
Cdd:cd15988  226 lwsscVVLPLLALTWMSAVLAMTDrRSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVVKCQMGG 291
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
386-643 1.10e-16

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: 80.86  E-value: 1.10e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYgLVWRVVVRNkvafFRHTTLFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFLC 465
Cdd:cd15997    3 ILTLITYLGCGISSIFLGITLVTY-LAFEKLRRD----YPSKILINLCTALLMLNLVFLLNSWLSSFNNYGLCITVAAFL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 466 HFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLmVMLGYLCPLGFAGVTL-------GLYLPQRKYL-WEGKCFLN 537
Cdd:cd15997   78 HYFLLASFTWMGLEAVHMYFALVKVFNIYIPNYILKF-CIAGWGIPAVVVALVLainkdfyGNELSSDSLHpSTPFCWIQ 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 538 GGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVS 617
Cdd:cd15997  157 DDVVFYISVVAYFCLIFLCN-ISMFITVLIQIRSMKAKKPSRNWKQGFLHDLKSVASLTFLLGLTWGFAFFAWGPVRIFF 235
                        250       260
                 ....*....|....*....|....*.
gi 568933246 618 HYAFSILNSLQGVFILVFGCLTDKKV 643
Cdd:cd15997  236 LYLFSICNTLQGFFIFVFHCLMKENV 261
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
387-653 1.24e-16

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: 80.28  E-value: 1.24e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYGLVwRVVVRNkvaffRHTTLFNMVICLLVADTCFL------GSPFLpsgyhsliCLV 460
Cdd:cd15991    4 LKIITYTTVSLSLVALLITFILLVLI-RTLRSN-----LHSIHKNLVAALFFSELIFLiginqtENPFV--------CTV 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 461 TAFLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHvvLSLMVMLGYLCPLGFAGVTLGLYlPQrKYLWEGKCFLNGGG 540
Cdd:cd15991   70 VAILLHYFYMSTFAWMFVEGLHIYRMLTEVRNINTGH--MRFYYVVGWGIPAIITGLAVGLD-PQ-GYGNPDFCWLSVQD 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 541 VMLYSFSEPVLAIVGVNGLVLVIAVlkllRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYA 620
Cdd:cd15991  146 TLIWSFAGPIGIVVIINTVIFVLAA----KASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGLMAVNSDTLSFHYL 221
                        250       260       270
                 ....*....|....*....|....*....|...
gi 568933246 621 FSILNSLQGVFILVFGCLTDKKVLEALRKRLRG 653
Cdd:cd15991  222 FAIFSCLQGIFIFFFHCIFNKEVRKHLKNVLTG 254
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
387-637 1.61e-16

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: 80.15  E-value: 1.61e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYglvwrVVVRNKVAFFRHTTLFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFLCH 466
Cdd:cd15258    4 LTFISYVGCGISAIFLAITILTY-----IAFRKLRRDYPSKIHMNLCAALLLLNLAFLLSSWIASFGSDGLCIAVAVALH 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 467 FFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMlGYlcplGFAGVTLGLYLPQRKYLWEGKCFLNGGGVMLYSF 546
Cdd:cd15258   79 YFLLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLCLV-GW----GLPALLVTLVLSVRSDNYGPITIPNGEGFQNDSF 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 547 ---SEPVLAIVGVNGLVLVIAVLKL------------LRPSLSEGPTVEKRQALVGVLKalliLTPIFGLTWGLGVATLF 611
Cdd:cd15258  154 cwiRDPVVFYITVVGYFGLTFLFNMvmlatvlvqicrLREKAQATPRKRALHDLLTLLG----LTFLLGLTWGLAFFAWG 229
                        250       260
                 ....*....|....*....|....*.
gi 568933246 612 DGSIVSHYAFSILNSLQGVFILVFGC 637
Cdd:cd15258  230 PFNLPFLYLFAIFNSLQGFFIFIWYC 255
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
329-376 3.14e-14

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.


Pssm-ID: 197639  Cd Length: 49  Bit Score: 67.41  E-value: 3.14e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568933246   329 GTLHCVFWDHrvfqGQGGWSDEGCEVHAANASITQCICQHLTAFSILM 376
Cdd:smart00303   1 FNPICVFWDE----SSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLM 44
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
393-651 3.92e-14

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: 73.10  E-value: 3.92e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 393 VGTGASVLALLVCLAIYGLVWRVVVRNkvaffRHTTLFNMVICLLVADTCFLGSPflPSGYHSLICLVTAFLCHFFYLAT 472
Cdd:cd15990   13 VGCGVSSLTLLLLIIIYVSVWRYIRSE-----RSVILINFCLSIISSNALILIGQ--TQTRNKVVCTLVAAFLHFFFLSS 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 473 FFWMLAQALvlaHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGlYLPQRKYLWEGKCFLNGGGVMLYSFSEPVLA 552
Cdd:cd15990   86 FCWVLTEAW---QSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVG-FTKAKGYGTVNYCWLSLEGGLLYAFVGPAAA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 553 IVGVNglvLVIAVLKLLRPSLSEGPTVEKRQALVGV-LKALLILTPIFGLTWGLGVATLFD-GSIVSHYAFSILNSLQGV 630
Cdd:cd15990  162 VVLVN---MVIGILVFNKLVSKDGITDKKLKERAGAsLWSSCVVLPLLALTWMSAVLAITDrRSALFQILFAVFDSLEGF 238
                        250       260
                 ....*....|....*....|.
gi 568933246 631 FILVFGCLTDKKVLEALRKRL 651
Cdd:cd15990  239 VIVMVHCILRREVQDAVKCRV 259
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
429-651 7.35e-13

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: 69.53  E-value: 7.35e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 429 LFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVmLGY 508
Cdd:cd15996   41 LMNLSTALLFLNLVFLLDGWIASFEIDELCITVAVLLHFFLLATFTWMGLEAIHMYIALVKVFNTYIRRYILKFCI-IGW 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 509 LCPLGFAGVTLGLYLPQRKYLWEGKCFLNGGG---------VMLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTV 579
Cdd:cd15996  120 GLPALIVSIVLASTNDNYGYGYYGKDKDGQGGdefcwiknpVVFYVTCAAYFGIMFLMNVAMFIVVMVQICGRNGKRSNR 199
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568933246 580 EKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRL 651
Cdd:cd15996  200 TLREEILRNLRSVVSLTFLLGMTWGFAFFAWGPVNLAFMYLFTIFNSLQGLFIFVFHCALKENVQKQWRRHL 271
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
332-375 1.00e-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: 62.71  E-value: 1.00e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568933246  332 HCVFWDHRVFqGQGGWSDEGCEVHAANASITQCICQHLTAFSIL 375
Cdd:pfam01825   2 QCVFWDFTNS-TTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
385-652 3.78e-12

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: 67.79  E-value: 3.78e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLsqVGTGASVLALLVCLAIYGLVWRVVVRNkvaffRHTTLFNMVICLLVADTCFLGSPflPSGYHSLICLVTAFL 464
Cdd:cd15989    6 PSVTLI--VGCGLSCLALITLAVVYAALWRYIRSE-----RSIILINFCLSIISSNILILVGQ--TQTHNKGICTMTTAF 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 465 CHFFYLATFFWMLAQALvlaHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGlYLPQRKYLWEGKCFLNGGGVMLY 544
Cdd:cd15989   77 LHFFFLASFCWVLTEAW---QSYMAVTGKIRTRLIRKRFLCLGWGLPALVVAISMG-FTKAKGYGTPHYCWLSLEGGLLY 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 545 SFSEPVLAIVGVNGLVLVIAVLKLL--------RPSLSEGPTVEKRQAL-----------------------VGVLKALL 593
Cdd:cd15989  153 AFVGPAAAVVLVNMVIGILVFNKLVsrdgildkKLKHRAGQMSEPHSGLtlkcakcgvvsttalsattasnaMASLWSSC 232
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 594 ILTPIFGLTWGLGVATLFDG-SIVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15989  233 VVLPLLALTWMSAVLAMTDKrSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFRCRLR 292
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
389-650 4.78e-12

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: 67.06  E-value: 4.78e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 389 LLSQVGTGASVLALLVCLAIYgLVWRVV--VRNK------VAF-FRHTTLFNM--VICLLVADTcflgspflpsgyHSLI 457
Cdd:cd15264    6 IIYYLGFSISLVALAVALIIF-LYFRSLrcLRNNihcnliVTFiLRNVTWFIMqnTLTEIHHQS------------NQWV 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 458 C--LVTAFlcHFFYLATFFWMLAQALVLaHQLLFVFHQLSKhVVLSLMVMLGYLCPLGFAGVTL-GLYLPQRKYLWEGKc 534
Cdd:cd15264   73 CrlIVTVY--NYFQVTNFFWMFVEGLYL-HTMIVWAYSADK-IRFWYYIVIGWCIPCPFVLAWAiVKLLYENEHCWLPK- 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 535 flNGGGVMLYSFSEPVLAIVGVNGLVLViAVLKLLRPSLSEGPTVEKRQALVGVlKALLILTPIFGLTWGLGVATLFDGS 614
Cdd:cd15264  148 --SENSYYDYIYQGPILLVLLINFIFLF-NIVWVLITKLRASNTLETIQYRKAV-KATLVLLPLLGITYMLFFINPGDDK 223
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 568933246 615 IVSH---YAFSILNSLQGVFILVFGCLTDKKVLEALRKR 650
Cdd:cd15264  224 TSRLvfiYFNTFLQSFQGLFVAVFYCFLNGEVRSAIRKK 262
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
386-634 7.90e-12

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


Pssm-ID: 320385 [Multi-domain]  Cd Length: 303  Bit Score: 66.82  E-value: 7.90e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGtgasvlallVCLAIYGLVWRVV---VRNKVAFFRHTTLF-NMVICLLVADTCFL----------------- 444
Cdd:cd15257    3 TLDIISTIG---------CVLSIAGLVITIIfhlHTRKLRKSSVTWVLlNLCSSLLLFNIIFTsgventnndyeistvpd 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 445 --GSPFLPSGYHSLI----CLVTAFLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLsLMVMLGYLCPLGFAGVT 518
Cdd:cd15257   74 reTNTVLLSEEYVEPdtdvCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFIL-QASAIGWGIPAVVVAIT 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 519 LG--------LYLPQRKYLWEGKCFLNGG-------GVMLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSlSEGPTVEKRQ 583
Cdd:cd15257  153 LGatyrfptsLPVFTRTYRQEEFCWLAALdknfdikKPLLWGFLLPVGLILITNVILFIMTSQKVLKKN-NKKLTTKKRS 231
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568933246 584 ALVGVLKALLILTpIFGLTWGLGVATLFDG---SIVSHYAFSILNSLQGVFILV 634
Cdd:cd15257  232 YMKKIYITVSVAV-VFGITWILGYLMLVNNdlsKLVFSYIFCITNTTQGVQIFI 284
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
387-651 5.27e-10

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: 61.00  E-value: 5.27e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYgLVWRVVVRNkvafFRHTTLFNMVICLLVADTCFLGSPFLpSGYHSL--ICLVTAFL 464
Cdd:cd15444    4 LTFITYIGCGLSAIFLSVTLVTY-IAFEKIRRD----YPSKILIQLCVALLLLNLVFLLDSWI-ALYKDIvgLCISVAVF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 465 CHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVmLGYLCPLGFAGVTLGLY-----LPQRKYLWEGK----CF 535
Cdd:cd15444   78 LHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCI-VGWGVPAVVVAIVLAVSkdnygLGSYGKSPNGStddfCW 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 536 LNGGGVMLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSlSEGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSI 615
Cdd:cd15444  157 INNNIVFYITVVGYFCVIFLLNISMFIVVLVQLCRIK-KQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAWGPVNL 235
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 568933246 616 VSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRL 651
Cdd:cd15444  236 AFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 271
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
431-646 1.44e-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: 59.47  E-value: 1.44e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 431 NMVICLLVADTCFLGSpfLPSGYHSLICLVTAFLCHFFYLATFFWMLAQALvlahqLLFVFHQLSKHVVLSLM---VMLG 507
Cdd:cd15993   42 NIAAALFLSELLFLLG--INRTENQFLCTVVAILLHYFFLSTFAWLFVQGL-----HIYRMQTEARNVNFGAMrfyYAIG 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 508 YLCPLGFAGVTLGLylPQRKYLWEGKCFLNGGGVMLYSFSEPVLAIVGVNGLVLVIAvlklLRPSLSEGPTVEKRQALVG 587
Cdd:cd15993  115 WGVPAIITGLAVGL--DPEGYGNPDFCWISIHDKLVWSFAGPIVVVIVMNGVMFLLV----ARMSCSPGQKETKKTSVLM 188
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568933246 588 VLKALLILTPIFGLTWGLGVATLFDGSIVSHYAFSILNSLQGVFILVFGCLTDKKVLEA 646
Cdd:cd15993  189 TLRSSFLLLLLISATWLFGLLAVNNSVLAFHYLHAILCCLQGLAVLLLFCVLNEEVQEA 247
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
458-651 1.59e-09

insect diuretic hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors that specifically bind to insect diuretic hormones found in Manduca sexta (moth) and Acheta domesticus (the house cricket), among others. Insect diuretic hormone and their GPCRs play critical roles in the regulation of water and ion balance. Thus they are attractive targets for developing new insecticides. Activation of the diuretic hormone receptors stimulate adenylate cyclase, thereby increasing cAMP levels in Malpighian tube. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of Gs family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx.


Pssm-ID: 320391 [Multi-domain]  Cd Length: 272  Bit Score: 59.69  E-value: 1.59e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 458 CLVTAFLCHFFYLATFFWMLAQALVLahQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGV-----TLGLYLPQRKYLWEG 532
Cdd:cd15263   71 CIILVVLLHYFHLTNFFWMFVEGLYL--YMLVVETFSGENIKLRVYAFIGWGIPAVVIVIwaivkALAPTAPNTALDPNG 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 533 ---KCFLNGGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQALVGVlKALLILTPIFGLTWGLGVAT 609
Cdd:cd15263  149 llkHCPWMAEHIVDWIFQGPAILVLAVN-LVFLVRIMWVLITKLRSANTVETQQYRKAA-KALLVLIPLLGITYILVIAG 226
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 568933246 610 LFDGS--IVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRL 651
Cdd:cd15263  227 PTEGIaaNIFEYVRAVLLSTQGFTVALFYCFLNTEVRNTLRHHF 270
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
390-652 4.16e-09

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: 58.05  E-value: 4.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 390 LSQVGTGASVLALLVCLAIYglvwrvvvrnkvAFFR---------HTTLFnmvICLLVADTCFLGspflpsgYHSLI--- 457
Cdd:cd15260    7 VYIGGYSVSLIALIISLAIF------------FSFRslrctritiHMNLF---ISFALNNLLWIV-------WYKLVvdn 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 458 ----------CLVTAFLCHFFYLATFFWMLAQALVLAHQLLFVFhqLSKHVVLSLMVMLGYLCPLGFAGVtlglYLPQRK 527
Cdd:cd15260   65 pevllenpiwCQALHVLLQYFMVCNYFWMFCEGLYLHTVLVVAF--ISEKSLMRWFIAIGWGVPLVITAI----YAGVRA 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 528 YLWEG--KCFLNGGGVMlYSFSEPVLAIVGVNgLVLVIAVLKL----LRPSLSEGPTVEKRQALvgvlKALLILTPIFGL 601
Cdd:cd15260  139 SLPDDteRCWMEESSYQ-WILIVPVVLSLLIN-LIFLINIVRVlltkLRATSPNPAPAGLRKAV----RATLILIPLLGL 212
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 568933246 602 TWglgVATLF------DGSIVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15260  213 QF---LLIPFrpepgaPLETIYQYVSALLTSLQGLCVAVLFCFCNGEVIAAIKRKWR 266
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
459-652 8.90e-09

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: 57.25  E-value: 8.90e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 459 LVTAFLcHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQRKyLWEGKcflNG 538
Cdd:cd15445   75 LVTAAY-NYFHVTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFICIGWCIPFPIIVAWAIGKLYYDNEK-CWFGK---RA 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 539 GGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQALVGVlKALLILTPIFGLTWGLGVATLFD---GSI 615
Cdd:cd15445  150 GVYTDYIYQGPMILVLLIN-FIFLFNIVRILMTKLRASTTSETIQYRKAV-KATLVLLPLLGITYMLFFVNPGEdeiSRI 227
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 568933246 616 VSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15445  228 VFIYFNSFLESFQGFFVSVFYCFLNSEVRSAVRKRWH 264
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
387-648 1.61e-08

Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320658  Cd Length: 255  Bit Score: 56.37  E-value: 1.61e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLaIYGLVWRVVVRNKVAFFRhttlfNMVICLLVADTCFL------GSPFLpsgyhsliCLV 460
Cdd:cd15992    4 LKTLTWSSVGVTLGFLLLTF-LFLLCLRALRSNKTSIRK-----NGATALFLSELVFIlginqaDNPFA--------CTV 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 461 TAFLCHFFYLATFFWMLAQALVLAHQLLFVfhQLSKHVVLSLMVMLGYLCPLGFAGVTLGlyLPQRKYLWEGKCFLNGGG 540
Cdd:cd15992   70 IAILLHFFYLCTFSWLFLEGLHIYRMLSEV--RDINYGPMRFYYLIGWGVPAFITGLAVG--LDPEGYGNPDFCWLSIYD 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 541 VMLYSFSEPVLAIVGVNGLVLVIAVlkllRPSLS-EGPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGSIVSHY 619
Cdd:cd15992  146 TLIWSFAGPVAFAVSMNVFLYILSS----RASCSaQQQSFEKKKGPVSGLRTAFTVLLLVSVTCLLALLSVNSDVILFHY 221
                        250       260
                 ....*....|....*....|....*....
gi 568933246 620 AFSILNSLQGVFILVFGCLTDKKVLEALR 648
Cdd:cd15992  222 LFAGFNCLQGPFIFLSHVVLLKEVRKALK 250
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
458-650 1.72e-08

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


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 56.12  E-value: 1.72e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 458 CLVTAFlcHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLpQRKYLWEGKcflN 537
Cdd:cd15446   74 CITTIY--NYFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYY-ENEQCWFGK---E 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 538 GGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQALVGVlKALLILTPIFGLTWGLGVATLFD---GS 614
Cdd:cd15446  148 PGKYIDYIYQGPVILVLLIN-FVFLFNIVRILMTKLRASTTSETIQYRKAV-KATLVLLPLLGITYMLFFVNPGEddiSQ 225
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 568933246 615 IVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKR 650
Cdd:cd15446  226 IVFIYFNSFLQSFQGFFVSVFYCFLNGEVRSAARKR 261
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
460-649 1.05e-07

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


Pssm-ID: 320650 [Multi-domain]  Cd Length: 290  Bit Score: 54.18  E-value: 1.05e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 460 VTAFLchfFYLAT-FFWMLAQALVLaHQLLFVFHqLSKHVVLSLMVMLGYlcplGFAGVTLGLYLPQRKYLWEGKCFLNG 538
Cdd:cd15984   99 VTFFL---YFLATnYYWILVEGLYL-HSLIFMAF-FSEKKYLWGFTLFGW----GLPAVFVTIWASVRATLADTGCWDLS 169
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 539 GGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSE--GPTVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDG--- 613
Cdd:cd15984  170 AGNLKWIIQVPILAAIVVN-FILFINIVRVLATKLREtnAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVFMAMPYTEvsg 248
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 568933246 614 ---SIVSHYAFsILNSLQGVFILVFGCLTDKKVLEALRK 649
Cdd:cd15984  249 ilwQVQMHYEM-LFNSFQGFFVAIIYCFCNGEVQAEIKK 286
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
386-653 1.74e-07

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: 53.26  E-value: 1.74e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVWRV-VVRNKVaffrHTTLFNMVICLLVA-----DTCFLGSPFLPSGYHSLICL 459
Cdd:cd15270    3 TVKIIYTVGYSISIVSLCVAVAILVAFRRLhCPRNYI----HIQLFFTFILKAIAvfikdAALFQEDDTDHCSMSTVLCK 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 460 VTAFLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHvvLSLMVMLGYlcplGFAGVTLGLYLPQRKYLWEGKCF-LNG 538
Cdd:cd15270   79 VSVVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRY--FWWLVLLGW----GLPTLCTGTWILCKLYFEDTECWdINN 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 539 GGVMLYSFSEPVLAIVGVN-GLVLVI--AVLKLLRPSLSEGPTVEKRQALVgvlKALLILTPIFGLTWGL-GVATLFDGS 614
Cdd:cd15270  153 DSPYWWIIKGPIVISVGVNfLLFLNIirILLKKLDPRQINFNNSAQYRRLS---KSTLLLIPLFGTHYIIfNFLPDYAGL 229
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 568933246 615 IVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLRG 653
Cdd:cd15270  230 GIRLYLELCLGSFQGFIVAVLYCFLNQEVQTEISRKWYG 268
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
386-635 2.28e-07

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: 52.88  E-value: 2.28e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYglvwrVVVR-NKVAFFRHTTL---FNMVICLLVADTCFLGSPFLPSGYHSLICLVT 461
Cdd:cd15442    3 TLVTISSAGCGVSMVFLIFTIILY-----FFLRfTYQKFKSEDAPkihVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKAL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 462 AFLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLmVMLGYLCPLGFAGVT-----LGLY----LPQRKYLweG 532
Cdd:cd15442   78 GGVTHYFLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKL-CLVGWGFPALVVTITgsinsYGAYtimdMANRTTL--H 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 533 KCFLNGGGVM-LYSFSEPVLAIVGV-NGLVLVIAVLKLLRPSlSEGPTVEKRQALVGVLkALLILTPIFGLTWGLGVATL 610
Cdd:cd15442  155 LCWINSKHLTvHYITVCGYFGLTFLfNTVVLGLVAWKIFHLQ-SATAGKEKCQAWKGGL-TVLGLSCLLGVTWGLAFFTY 232
                        250       260
                 ....*....|....*....|....*
gi 568933246 611 FDGSIVSHYAFSILNSLQGVFILVF 635
Cdd:cd15442  233 GSMSVPTVYIFALLNSLQGLFIFIW 257
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
458-649 1.31e-06

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


Pssm-ID: 320648 [Multi-domain]  Cd Length: 289  Bit Score: 50.70  E-value: 1.31e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 458 CLVTAFLCHFFYLATFFWMLAQALVLaHQLLFV-FHQLSKHvvLSLMVMLGYlcplGFAGVTLGLYLPQRKYLWEGKCFL 536
Cdd:cd15982   95 CKIAVVMFIYFLATNYYWILVEGLYL-HSLIFVaFFSDTKY--LWGFTLIGW----GFPAVFVAAWAVVRATLADARCWE 167
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 537 NGGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTV--EKRQALVGVLKALLILTPIFGLTW--GLGVATLFD 612
Cdd:cd15982  168 LSAGDIKWIYQAPILAAIGLN-FILFLNTVRVLATKIWETNAVgyDTRKQYRKLAKSTLVLVLVFGVHYivFVCLPHTFT 246
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 568933246 613 GSI--VSHYAFSILNSLQGVFILVFGCLTDKKVLEALRK 649
Cdd:cd15982  247 GLGweIRMHCELFFNSFQGFFVSIIYCYCNGEVQTEIKK 285
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
385-649 4.20e-06

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


Pssm-ID: 320400 [Multi-domain]  Cd Length: 285  Bit Score: 49.31  E-value: 4.20e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 385 PTLDLLSQVGTGASVLALLVCLAIYGLVWRV-VVRNKVaffrHTTLFnmVICLLVADTCFLGSPFL-------------P 450
Cdd:cd15272    2 PSIRLMYNIGYGLSLVSLLIAVIIMLYFKKLhCPRNTI----HINLF--VSFILRAVLSFIKENLLvqgvgfpgdvyydS 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 451 SGYHSLICLVTAFLCHFFY-------LATFFWMLAQALVLaHQLLFVfHQLSKHVVLSLMVMLGYLCPLGFAgvtlglyL 523
Cdd:cd15272   76 NGVIEFKDEGSHWECKLFFtmfnyilGANYMWIFVEGLYL-HMLIFV-AVFSENSRVKWYILLGWLSPLLFV-------L 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 524 PQ---RKYLWEGKCF-LNGGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQALVGVL-KALLILTPI 598
Cdd:cd15272  147 PWvfvRATLEDTLCWnTNTNKGYFWIIRGPIVISIAIN-FLFFINIVRVLFTKLKASNTQESRPFRYRKLaKSTLVLIPL 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568933246 599 FGLTW----GLGVATLFDGS-IVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRK 649
Cdd:cd15272  226 FGVHYmvfvVLPDSMSSDEAeLVWLYFEMFFNSFQGFIVALLFCFLNGEVQSEIKK 281
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
390-649 7.53e-06

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


Pssm-ID: 341343 [Multi-domain]  Cd Length: 274  Bit Score: 48.23  E-value: 7.53e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 390 LSQVGTGASVLALLVCLAIYgLVWRVVVRNKVAFfrHTTLFNMVICLLVADTCFLGSPFLPS---GYHSLICLVTAFLCH 466
Cdd:cd15274    7 LAIVGHSLSIATLLISLGIF-FFFRSLSCQRVTL--HKNLFLSYILNSIIIIIHLVAVVPNGelvARNPVSCKILHFIHQ 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 467 FFYLATFFWMLAQALVLaHQLLFVFHQLSKHvvlslMVMLGYLCPLGFAGVTLGLYLPQRKYLWEGKCFLNGGGVMLYSF 546
Cdd:cd15274   84 YMMGCNYFWMLCEGIYL-HTLIVVAVFAEKQ-----RLMWYYLLGWGFPLIPTTIHAITRAVYYNDNCWLSSETHLLYII 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 547 SEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKrQALVGVLKALLILTPIFG-----LTWGLGVATLFDgsiVSHYAF 621
Cdd:cd15274  158 HGPIMAALVVN-FFFLLNIVRVLVTKLRETHEAES-HMYLKAVKATLILVPLLGiqfvlFPWRPSGKILGK---IYDYVM 232
                        250       260
                 ....*....|....*....|....*...
gi 568933246 622 SILNSLQGVFILVFGCLTDKKVLEALRK 649
Cdd:cd15274  233 HSLIHFQGFFVATIFCFCNGEVQATLKR 260
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
431-643 9.81e-06

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


Pssm-ID: 320559 [Multi-domain]  Cd Length: 268  Bit Score: 47.83  E-value: 9.81e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 431 NMVICLLVADTCFLGSPFLPSGYHSLICLVTAFLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLmVMLGYLC 510
Cdd:cd15443   43 NLLGSLFLLNGSFLLSPPLATSQSTWLCRAAAALLHYSLLCCLTWMAIEGFHLYLLLVKVYNIYIRRYVLKL-CVLGWGL 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 511 P-------LGFAGVTLGLYLPQ--RKYLWEGKCFLNGGGVMlYSFSEPVLAIVGVNGLVLVIAVLKLLR--PSLSEGPTV 579
Cdd:cd15443  122 PalivllvLIFKREAYGPHTIPtgTGYQNASMCWITSSKVH-YVLVLGYAGLTSLFNLVVLAWVVRMLRrlRSRKQELGE 200
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568933246 580 EKRQALVGVLKalliLTPIFGLTWGLGVATLFDGSIVSHYAFSILNSLQGVFILVFGCLTDKKV 643
Cdd:cd15443  201 RARRDWVTVLG----LTCLLGTTWALAFFSFGVFLIPQLFLFTIINSLYGFFICLWYCTQRRRS 260
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
458-652 8.18e-05

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


Pssm-ID: 320652 [Multi-domain]  Cd Length: 269  Bit Score: 45.18  E-value: 8.18e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 458 CLVTAFLCHFFYLATFFWMLAQALVLaHQLLFVFHQLSKHVVLSLMVmlGYlcplGFAGVTLGLYLPQRKYLWEGKCF-L 536
Cdd:cd15986   79 CKVSLVILQYCIMANFYWLLVEGLYL-HTLLVVIFSENRHFIVYLLI--GW----GIPTVFIIAWIVARIYLEDTGCWdT 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 537 NGGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQALVGVL-KALLILTPIFGLTWglGVATLFDGSI 615
Cdd:cd15986  152 NDHSVPWWVIRIPIIISIILN-FILFISIIRILLQKLRSPDVGGNDQSQYKRLaKSTLLLIPLFGVHY--IVFVYFPDSS 228
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568933246 616 VSHYAFSI---LNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15986  229 SSNYQIFFelcLGSFQGLVVAILYCFLNSEVQGELKRKWR 268
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
386-653 1.22e-04

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


Pssm-ID: 341353 [Multi-domain]  Cd Length: 279  Bit Score: 44.73  E-value: 1.22e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVWRV-VVRNKVaffrHTTLFNMVI----CLLVADTCF-----------LGSPFL 449
Cdd:cd15929    3 SLQVMYTVGYSLSLAALVLALAILLGLRKLhCTRNYI----HANLFASFIlralSVLVKDALLprrysqkgdqdLWSTLL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 450 PSGyHSLICLVTAFLCHFFYLATFFWMLAQALVLaHQLLfVFHQLSKHVVLSLMVMLGYLCPLGFAgVTLGLYlpqrKYL 529
Cdd:cd15929   79 SNQ-ASLGCRVAQVLMQYCVAANYYWLLVEGLYL-HTLL-VLAVFSERSIFRLYLLLGWGAPVLFV-VPWGIV----KYL 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 530 WEG-KCF-LNGGGVMLYSFSEPVLAIVGVNGLVLvIAVLKLLRPSLsEGPTVEKRQALVGVLKALLILTPIFGL------ 601
Cdd:cd15929  151 YENtGCWtRNDNMAYWWIIRLPILLAILINFFIF-VRILKILVSKL-RANQMCKTDYKFRLAKSTLTLIPLLGVhevvfa 228
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 602 -------TWGLGVATLFdgsivshyaFSI-LNSLQGVFILVFGCLTDKKVLEALRKRLRG 653
Cdd:cd15929  229 fvtdeqaRGTLRFIKLF---------FELfLSSFQGLLVAVLYCFANKEVQSELRKKWHR 279
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
49-95 1.79e-04

Hormone receptor domain; This extracellular domain contains four conserved cysteines that probably for disulphide bridges. The domain is found in a variety of hormone receptors. It may be a ligand binding domain.


Pssm-ID: 397086  Cd Length: 64  Bit Score: 40.05  E-value: 1.79e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568933246   49 CPEDF-SVVSWNVTKAGFVAQAPCP-----VNKKGVVKRLCGTDGIWRPVQNT 95
Cdd:pfam02793   4 CPRTWdGILCWPRTPAGETVEVPCPdyfsgFDPRGNASRNCTEDGTWSEHPPS 56
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
454-643 1.81e-04

insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of hormone receptors; member of the class B secretin-like seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Bombyx mori (silk worm) and its closely related proteins from arthropods. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320390 [Multi-domain]  Cd Length: 270  Bit Score: 43.97  E-value: 1.81e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 454 HSLICLVTAFLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMLGYLCPLGFAGVTLGlylpqrkyLWEG- 532
Cdd:cd15262   78 NAVVCRLLSIFERAARNAVFACMFVEGFYLHRLIVAVFAEKSSIRFLYVIGAVLPLFPVIIWAIIRA--------LHNDh 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 533 KCFLNGGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQAlvgVLKALLILTPIFGLTWglgVATLF- 611
Cdd:cd15262  150 SCWVVDIEGVQWVLDTPRLFILLVN-TVLLVDIIRVLVTKLRNTEENSQTKS---TTRATLFLVPLFGLHF---VITAYr 222
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 568933246 612 ------DGSIVSHYAFSILNSLQGVFILVFGCLTDKKV 643
Cdd:cd15262  223 pstddcDWEDIYYYANYLIEGLQGFLVAILFCYINKEV 260
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
386-652 3.01e-04

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: 43.18  E-value: 3.01e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVWRV-VVRNKVaffrHTTLFNMVIclLVADTCFLGSPFLPSGYHSLICLVTAFL 464
Cdd:cd15271    3 TVKLLYTVGYGTSLTSLITAVLIFCTFRKLhCTRNYI----HINLFVSFI--LRALAVFIKDAVLFADESVDHCTMSTVA 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 465 C-------HFFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVmlGYLCPLgfagVTLGLYLPQRKYLWEGKCFLN 537
Cdd:cd15271   77 CkaavtffQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILI--GWGAPS----VTVTVWVLTRLQYDNRGCWDD 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 538 GGGVMLYSFSEPVLAIVGVNGLVLVIAVLKLLRPSLSEGPTVEKRQALVGVLKALLILTPIFGLTWglGVATLFD---GS 614
Cdd:cd15271  151 LESRIWWIIKTPILLSVFVNFLIFINVIRILVQKLKSPDVGGNDTSHYMRLAKSTLLLIPLFGVHY--VVFAFFPehvGV 228
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 568933246 615 IVSHYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15271  229 EARLYFELVLGSFQGFIVALLYCFLNGEVQAEIKKRLG 266
HormR smart00008
Domain present in hormone receptors;
49-91 3.83e-04

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 39.42  E-value: 3.83e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568933246    49 CPEDF-SVVSWNVTKAGFVAQAPCP-----VNKKGVVKRLCGTDGIWRP 91
Cdd:smart00008   5 CPATWdGIICWPQTPAGQLVEVPCPkyfsgFSYKTGASRNCTENGGWSP 53
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
386-653 7.17e-04

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


Pssm-ID: 320596 [Multi-domain]  Cd Length: 268  Bit Score: 42.03  E-value: 7.17e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVWRV-VVRNkvafFRHTTLFNMVICLLVA-----DTCFLGSPFLPSGYHSLICL 459
Cdd:cd15930    3 TVKIIYTVGYSLSLTSLTTAMIILCLFRKLhCTRN----YIHMNLFVSFILRAIAvfikdAVLFSSEDVDHCFVSTVGCK 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 460 VTAFLCHFFYLATFFWMLAQALVLAHQLLFVFHQLSKHvvLSLMVMLGYlcplGFAGVTLGLYLPQRKYLWEGKCF-LNG 538
Cdd:cd15930   79 ASMVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRY--FWWYVLIGW----GAPTVFVTVWIVARLYFEDTGCWdIND 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 539 GGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSL------SEGPTVEKRQAlvgvlKALLILTPIFGLTWGLGVATLFD 612
Cdd:cd15930  153 ESPYWWIIKGPILISILVN-FVLFINIIRILLQKLrspdigGNESSQYKRLA-----RSTLLLIPLFGIHYIVFAFFPEN 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 568933246 613 GSIVSHYAFSI-LNSLQGVFILVFGCLTDKKVLEALRKRLRG 653
Cdd:cd15930  227 ISLGIRLYFELcLGSFQGFVVAVLYCFLNGEVQAEIKRKWRS 268
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
387-635 7.39e-04

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: 42.12  E-value: 7.39e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 387 LDLLSQVGTGASVLALLVCLAIYgLVWRVVVRNKVAFFRhttlFNMVICLLVADTCFLGSPFLPSGYHSLICLVTAFLCH 466
Cdd:cd15995    4 LTILTYVGCIISALASVFTIAFY-LCSRRKPRDYTIYVH----MNLLLAIFLLDTSFLISEPLALTGSEAACRAGGMFLH 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 467 FFYLATFFWMLAQALVLAHQLLFVFHQLSKHVVLSLMVMlGYLCPLGFAGV------------TLGLYLPQRKYLWEGKC 534
Cdd:cd15995   79 FSLLACLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAV-GWGLPIFLVTLiflvdqdnygpiILAVHRSPEKVTYATIC 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 535 FLNGGGVMLYSFSEPVLAIVGVNGLVLVIAVLKLLRpslsegptVEKRQALVGVLKALLILTPIFGLTWGLGVATLFDGS 614
Cdd:cd15995  158 WITDSLISNITNLGLFSLVFLFNMAMLATMVVEILR--------LRPRTHKWSHVLTLLGLSLVLGIPWALAFFSFASGT 229
                        250       260
                 ....*....|....*....|...
gi 568933246 615 --IVSHYAFSILNSLQGVFILVF 635
Cdd:cd15995  230 fqLVIVYLFTIINSLQGFLIFLW 252
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
461-652 1.15e-03

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


Pssm-ID: 320389 [Multi-domain]  Cd Length: 282  Bit Score: 41.58  E-value: 1.15e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 461 TAFLCHFFYL-------ATFFWMLAQALVLAHQLLFVFhqLSKHVVLSLMVMLGYLCPLGFAGVTLGLYLPQRKylwEGK 533
Cdd:cd15261   84 TPILCEGFYVlleyaktVMFMWMFIEGLYLHNIIVVSV--FSGKPNYLFYYILGWGIPIVHTSAWAIVTLIKMK---VNR 158
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 534 CFLNgggvmlYSFSE-------PVLAIVGVNgLVLVIAVLKLLRPSLSEGPTVEKRQALVGVlKALLILTPIFGLTWGLG 606
Cdd:cd15261  159 CWFG------YYLTPyywilegPRLAVILIN-LFFLLNIIRVLVSKLRESHSREIEQVRKAV-KAAIVLLPLLGITNILQ 230
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568933246 607 -VATLFDGSIVS----HYAFSILNSLQGVFILVFGCLTDKKVLEALRKRLR 652
Cdd:cd15261  231 mIPPPLTSVIVGfavwSYSTHFLTSFQGFFVALIYCFLNGEVKNVLKKFWR 281
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
386-650 3.60e-03

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


Pssm-ID: 320394 [Multi-domain]  Cd Length: 280  Bit Score: 40.11  E-value: 3.60e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 386 TLDLLSQVGTGASVLALLVCLAIYGLVWRV-VVRNkvafFRHTTLFNMVI----CLLVADTCFLGSPF-----------L 449
Cdd:cd15266    3 TLQLIYTIGYSLSLISLSLALLILLLLRKLhCTRN----YIHMNLFASFIlralAVLIKDIVLYSTYSkrpddetgwisY 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 450 PSGYHSLICLVTAFLCHFFYLATFFWMLAQALVLaHQLLFVfHQLSKHVVLSLMVMLGYLCPLGFA---GVTlglylpqR 526
Cdd:cd15266   79 LSEESSTSCRVAQVFMHYFVGANYFWLLVEGLYL-HTLLVT-AVLSERRLLKKYMLIGWGTPVLFVvpwGVA-------K 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933246 527 KYLWEGKCF-LNGGGVMLYSFSEPVLAIVGVNgLVLVIAVLKLLRPSLsEGPTVEKRQALVGVLKALLILTPIFGLTwgL 605
Cdd:cd15266  150 ILLENTGCWgRNENMGIWWIIRGPILLCITVN-FYIFLKILKLLLSKL-KAQQMRFTDYKYRLARSTLVLIPLLGIH--E 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 568933246 606 GVATLFDGSIVSHYAFSI-------LNSLQGVFILVFGCLTDKKVLEALRKR 650
Cdd:cd15266  226 VVFSFITDEQVEGFSRHIrlfiqltLSSFQGFLVAVLYCFANGEVKAELKKR 277
 
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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