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Conserved domains on  [gi|568976541|ref|XP_006534625|]
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glucagon-like peptide 2 receptor isoform X2 [Mus musculus]

Protein Classification

hormone receptor( domain architecture ID 12039890)

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

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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 ...
137-405 1.45e-154

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 cd15266:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 280  Bit Score: 439.95  E-value: 1.45e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSESGWMSYLS 216
Cdd:cd15266    1 LLTLQLIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDIVLYSTYSKRPDDETGWISYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 E-ISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAV 295
Cdd:cd15266   81 EeSSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVVPWGVAKILLENTGCWGR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 296 NENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGFS 375
Cdd:cd15266  161 NENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYKYRLARSTLVLIPLLGIHEVVFSFITDEQVEGFS 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 568976541 376 RLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15266  241 RHIRLFIQLTLSSFQGFLVAVLYCFANGEV 270
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
53-122 1.83e-16

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: 73.56  E-value: 1.83e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568976541   53 GVFCNGTFDKYVCWPHSFPGN-VSVPCPSYLPWWNKEspGRAYRHCLAQGTWQKQENStdtwqDESECSEN 122
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGEtVEVPCPDYFSGFDPR--GNASRNCTEDGTWSEHPPS-----NYSNCTSN 64
 
Name Accession Description Interval E-value
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
137-405 1.45e-154

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: 439.95  E-value: 1.45e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSESGWMSYLS 216
Cdd:cd15266    1 LLTLQLIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDIVLYSTYSKRPDDETGWISYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 E-ISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAV 295
Cdd:cd15266   81 EeSSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVVPWGVAKILLENTGCWGR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 296 NENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGFS 375
Cdd:cd15266  161 NENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYKYRLARSTLVLIPLLGIHEVVFSFITDEQVEGFS 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 568976541 376 RLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15266  241 RHIRLFIQLTLSSFQGFLVAVLYCFANGEV 270
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
137-394 1.06e-85

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: 263.37  E-value: 1.06e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541  137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSysrRPDSESGWMsyls 216
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNK---QDLDHCSWV---- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541  217 eisaSCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFV--RASLENTGCWA 294
Cdd:pfam00002  74 ----GCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCWL 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541  295 VNENkKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYK--YRLAKSTLLLILLMGVHE--FLFTFFTDdq 370
Cdd:pfam00002 150 SNEN-GLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKqyRRLAKSTLLLLPLLGITWvfGLFAFNPE-- 226
                         250       260
                  ....*....|....*....|....
gi 568976541  371 vqGFSRLIRLFIQLTLSSFHGFLV 394
Cdd:pfam00002 227 --NTLRVVFLYLFLILNSFQGFFV 248
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
53-122 1.83e-16

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: 73.56  E-value: 1.83e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568976541   53 GVFCNGTFDKYVCWPHSFPGN-VSVPCPSYLPWWNKEspGRAYRHCLAQGTWQKQENStdtwqDESECSEN 122
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGEtVEVPCPDYFSGFDPR--GNASRNCTEDGTWSEHPPS-----NYSNCTSN 64
HormR smart00008
Domain present in hormone receptors;
52-122 2.41e-12

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 62.15  E-value: 2.41e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568976541    52 SGVFCNGTFDKYVCWPHSFPGN-VSVPCPSYLPWWNKEspGRAYRHCLAQGTWqkqensTDTWQDESECSEN 122
Cdd:smart00008   1 TDLGCPATWDGIICWPQTPAGQlVEVPCPKYFSGFSYK--TGASRNCTENGGW------SPPFPNYSNCTSN 64
 
Name Accession Description Interval E-value
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
137-405 1.45e-154

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: 439.95  E-value: 1.45e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSESGWMSYLS 216
Cdd:cd15266    1 LLTLQLIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDIVLYSTYSKRPDDETGWISYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 E-ISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAV 295
Cdd:cd15266   81 EeSSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVVPWGVAKILLENTGCWGR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 296 NENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGFS 375
Cdd:cd15266  161 NENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYKYRLARSTLVLIPLLGIHEVVFSFITDEQVEGFS 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 568976541 376 RLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15266  241 RHIRLFIQLTLSSFQGFLVAVLYCFANGEV 270
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
137-405 2.59e-142

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: 409.13  E-value: 2.59e-142
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSESGWMSYLS 216
Cdd:cd15929    1 LSSLQVMYTVGYSLSLAALVLALAILLGLRKLHCTRNYIHANLFASFILRALSVLVKDALLPRRYSQKGDQDLWSTLLSN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 EISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVN 296
Cdd:cd15929   81 QASLGCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLLLGWGAPVLFVVPWGIVKYLYENTGCWTRN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 297 ENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGFSR 376
Cdd:cd15929  161 DNMAYWWIIRLPILLAILINFFIFVRILKILVSKLRANQMCKTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEQARGTLR 240
                        250       260
                 ....*....|....*....|....*....
gi 568976541 377 LIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15929  241 FIKLFFELFLSSFQGLLVAVLYCFANKEV 269
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
138-405 2.10e-93

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


Pssm-ID: 320395 [Multi-domain]  Cd Length: 281  Bit Score: 284.41  E-value: 2.10e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 138 STLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSESGWMSYLSE 217
Cdd:cd15267    4 SSFQVMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASSVLVIDGLLRTRYSQKIEDDLSSTWLSDE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 218 ISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVNE 297
Cdd:cd15267   84 AVAGCRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPALFVVPWVVVKCLYENVQCWTSND 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 298 NKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGFSRL 377
Cdd:cd15267  164 NMGFWWILRFPVFLAILINFFIFVRIIQILVSKLRARQMHYTDYKFRLAKSTLTLIPLLGIHEVVFAFVTDEHAQGTLRS 243
                        250       260
                 ....*....|....*....|....*...
gi 568976541 378 IRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15267  244 AKLFFDLFLSSFQGLLVAVLYCFLNKEV 271
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
137-405 3.17e-89

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


Pssm-ID: 320651 [Multi-domain]  Cd Length: 280  Bit Score: 273.73  E-value: 3.17e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSESGWMSYLS 216
Cdd:cd15985    1 MVSFRMLYTVGYTLSLLTLVSALLILTSIRKLHCTRNYIHANLFASFILRAVSVIVKDTLLERRWGREIMRVADWGELLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 EISA-SCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAV 295
Cdd:cd15985   81 HKAAiGCRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVLFVVPWMLAKYLKENKECWAL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 296 NENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGFS 375
Cdd:cd15985  161 NENMAYWWIIRIPILLASLINLLIFMRILKVILSKLRANQKGYADYKLRLAKATLTLIPLFGIHEVVFIFATDEQTTGIL 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 568976541 376 RLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15985  241 RYIKVFFTLFLNSFQGFLVAVLYCFANKEV 270
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
137-394 1.06e-85

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: 263.37  E-value: 1.06e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541  137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSysrRPDSESGWMsyls 216
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNK---QDLDHCSWV---- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541  217 eisaSCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFV--RASLENTGCWA 294
Cdd:pfam00002  74 ----GCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCWL 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541  295 VNENkKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYK--YRLAKSTLLLILLMGVHE--FLFTFFTDdq 370
Cdd:pfam00002 150 SNEN-GLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKqyRRLAKSTLLLLPLLGITWvfGLFAFNPE-- 226
                         250       260
                  ....*....|....*....|....
gi 568976541  371 vqGFSRLIRLFIQLTLSSFHGFLV 394
Cdd:pfam00002 227 --NTLRVVFLYLFLILNSFQGFFV 248
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
137-405 2.49e-80

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: 250.43  E-value: 2.49e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYnsysrrpdsESGWMSYLS 216
Cdd:cd15930    1 YLTVKIIYTVGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKDAVLF---------SSEDVDHCF 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 EISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVN 296
Cdd:cd15930   72 VSTVGCKASMVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVWIVARLYFEDTGCWDIN 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 297 ENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRD---YKyRLAKSTLLLILLMGVHEFLFTFFTDDqvqg 373
Cdd:cd15930  152 DESPYWWIIKGPILISILVNFVLFINIIRILLQKLRSPDIGGNEssqYK-RLARSTLLLIPLFGIHYIVFAFFPEN---- 226
                        250       260       270
                 ....*....|....*....|....*....|..
gi 568976541 374 FSRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15930  227 ISLGIRLYFELCLGSFQGFVVAVLYCFLNGEV 258
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
137-405 4.18e-77

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


Pssm-ID: 341342 [Multi-domain]  Cd Length: 279  Bit Score: 242.55  E-value: 4.18e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSES--GWMSY 214
Cdd:cd15268    1 LLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYSTAAQQHQwdGLLSY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 215 lsEISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWA 294
Cdd:cd15268   81 --QDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFVIPWGIVKYLYEDEGCWT 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 295 VNENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGF 374
Cdd:cd15268  159 RNSNMNYWLIIRLPILFAIGVNFLIFIRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGT 238
                        250       260       270
                 ....*....|....*....|....*....|.
gi 568976541 375 SRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15268  239 LRFVKLFTELSFTSFQGLMVAILYCFVNNEV 269
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
137-405 4.78e-75

secretin receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Secretin receptor is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include vasoactive intestinal peptide (VIP), growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors, and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Secretin, a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion. Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptor, which is expressed in the brain, pancreas, stomach, kidney, and liver.


Pssm-ID: 320403 [Multi-domain]  Cd Length: 271  Bit Score: 236.95  E-value: 4.78e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYnsysrrpdsESGWMSYLS 216
Cdd:cd15275    1 FMYLKTMYTVGYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFIKDAVLF---------SSEDDNHCD 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 EISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVN 296
Cdd:cd15275   72 IYTVGCKVAMVFSNYCIMANYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFIISWAIARYLHENEGCWDTR 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 297 ENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMC---FRDYKyRLAKSTLLLILLMGVHEFLFTFFTDDqVQG 373
Cdd:cd15275  152 RNAWIWWIIRGPVILSIFVNFILFLNILRILMRKLRAPDMRgneFSQYK-RLAKSTLLLIPLFGLHYILFAFFPED-VSS 229
                        250       260       270
                 ....*....|....*....|....*....|..
gi 568976541 374 FSRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15275  230 GTMEIWLFFELALGSFQGFVVAVLYCFLNGEV 261
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
137-407 1.15e-74

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: 236.13  E-value: 1.15e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPD---SESGWMS 213
Cdd:cd15272    1 LPSIRLMYNIGYGLSLVSLLIAVIIMLYFKKLHCPRNTIHINLFVSFILRAVLSFIKENLLVQGVGFPGDvyyDSNGVIE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 214 YLSEISA-SCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGC 292
Cdd:cd15272   81 FKDEGSHwECKLFFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLLFVLPWVFVRATLEDTLC 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 293 WAVNENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRA-HQMCFRDYKYR-LAKSTLLLILLMGVHEFLFTFFTDDQ 370
Cdd:cd15272  161 WNTNTNKGYFWIIRGPIVISIAINFLFFINIVRVLFTKLKAsNTQESRPFRYRkLAKSTLVLIPLFGVHYMVFVVLPDSM 240
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 568976541 371 VQGFSRLIRLFIQLTLSSFHGFLVALQYGFASREVPT 407
Cdd:cd15272  241 SSDEAELVWLYFEMFFNSFQGFIVALLFCFLNGEVQS 277
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
137-405 3.50e-74

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: 234.43  E-value: 3.50e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSESGWMSYLs 216
Cdd:cd15041    1 LLVVYYIYLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFLSFILRAVFWIIWDLLVVYDRLTSSGVETVLMQNP- 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 eisASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVN 296
Cdd:cd15041   80 ---VGCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSSLKLYYAIGWGLPLVIVVIWAIVRALLSNESCWISY 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 297 ENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGfsR 376
Cdd:cd15041  157 NNGHYEWILYGPNLLALLVNLFFLINILRILLTKLRSHPNAEPSNYRKAVKATLILIPLFGIQYLLTIYRPPDGSEG--E 234
                        250       260
                 ....*....|....*....|....*....
gi 568976541 377 LIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15041  235 LVYEYFNAILNSSQGFFVAVIYCFLNGEV 263
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
139-405 5.92e-74

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


Pssm-ID: 320393 [Multi-domain]  Cd Length: 289  Bit Score: 234.58  E-value: 5.92e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 139 TLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYnSYSRRPDSESGWMSYLSEI 218
Cdd:cd15265    3 RLYLIYTVGYSISLVSLTVAVFILGYFRRLHCTRNYIHMHLFVSFMLRAVSIFVKDAVLY-SGSGLDELERPSMEDLKSI 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 219 S----------ASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLE 288
Cdd:cd15265   82 VeappvdksqyVGCKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVFVIPWASVRATLA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 289 NTGCWAVNENkKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYK--YR-LAKSTLLLILLMGVHEFLFTF 365
Cdd:cd15265  162 DTRCWDLSAG-NYKWIYQVPILAAIVVNFILFLNIVRVLATKLRETNAGRCDTRqqYRkLAKSTLVLIPLFGVHYIVFMG 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 568976541 366 FTDDQVqGFSRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15265  241 MPYTEV-GLLWQIRMHYELFFNSFQGFFVAIIYCFCNGEV 279
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
139-405 4.19e-69

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


Pssm-ID: 320397 [Multi-domain]  Cd Length: 268  Bit Score: 221.27  E-value: 4.19e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 139 TLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYnsysrrpdsESGWMSYLSEI 218
Cdd:cd15269    3 TVKTGYTIGHSLSLISLTAAMIILCLFRKLHCTRNYIHMHLFMSFILRAIAVFIKDAVLF---------ESGEEDHCSVA 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 219 SASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVNEN 298
Cdd:cd15269   74 SVGCKAAMVFFQYCIMANFFWLLVEGLYLHTLLAVSFFSERKYFWWYILIGWGAPSVFITAWSVARIYFEDVGCWDTIIE 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 299 KKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYK--YRLAKSTLLLILLMGVHEFLFTFFTDDqvqgFSR 376
Cdd:cd15269  154 SLLWWIIKTPILVSILVNFILFICIIRILVQKLHSPDIGRNESSqySRLAKSTLLLIPLFGIHYIMFAFFPDN----FKA 229
                        250       260
                 ....*....|....*....|....*....
gi 568976541 377 LIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15269  230 EVKLVFELILGSFQGFVVAVLYCFLNGEV 258
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
137-405 5.14e-69

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: 221.14  E-value: 5.14e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSrrpdsesgwMSYLS 216
Cdd:cd15271    1 FSTVKLLYTVGYGTSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALAVFIKDAVLFADES---------VDHCT 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 EISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAvN 296
Cdd:cd15271   72 MSTVACKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVWVLTRLQYDNRGCWD-D 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 297 ENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQM--CFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDqvqgF 374
Cdd:cd15271  151 LESRIWWIIKTPILLSVFVNFLIFINVIRILVQKLKSPDVggNDTSHYMRLAKSTLLLIPLFGVHYVVFAFFPEH----V 226
                        250       260       270
                 ....*....|....*....|....*....|.
gi 568976541 375 SRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15271  227 GVEARLYFELVLGSFQGFIVALLYCFLNGEV 257
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
138-407 9.83e-69

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: 220.44  E-value: 9.83e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 138 STLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDSESgwmsylse 217
Cdd:cd15270    2 STVKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFIKDAALFQEDDTDHCSMS-------- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 218 iSASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVNE 297
Cdd:cd15270   74 -TVLCKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCKLYFEDTECWDINN 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 298 NKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCF--RDYKYRLAKSTLLLILLMGVHEFLFTFFTDdqvqGFS 375
Cdd:cd15270  153 DSPYWWIIKGPIVISVGVNFLLFLNIIRILLKKLDPRQINFnnSAQYRRLSKSTLLLIPLFGTHYIIFNFLPD----YAG 228
                        250       260       270
                 ....*....|....*....|....*....|..
gi 568976541 376 RLIRLFIQLTLSSFHGFLVALQYGFASREVPT 407
Cdd:cd15270  229 LGIRLYLELCLGSFQGFIVAVLYCFLNQEVQT 260
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
140-405 1.42e-67

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: 217.36  E-value: 1.42e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFY-NSYSRRPDSESGWMSylsei 218
Cdd:cd15986    4 VKTIYTLGHSVSLIALTTGSTILCLFRKLHCTRNYIHLNLFFSFILRAISVLVKDDILYsSSNTEHCTVPPSLIG----- 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 219 sasCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEpTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVNEN 298
Cdd:cd15986   79 ---CKVSLVILQYCIMANFYWLLVEGLYLHTLLV-VIFSENRHFIVYLLIGWGIPTVFIIAWIVARIYLEDTGCWDTNDH 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 299 KKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRD---YKyRLAKSTLLLILLMGVHEFLFTFFTDDQVQGFs 375
Cdd:cd15986  155 SVPWWVIRIPIIISIILNFILFISIIRILLQKLRSPDVGGNDqsqYK-RLAKSTLLLIPLFGVHYIVFVYFPDSSSSNY- 232
                        250       260       270
                 ....*....|....*....|....*....|
gi 568976541 376 rliRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15986  233 ---QIFFELCLGSFQGLVVAILYCFLNSEV 259
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
139-405 3.19e-64

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


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 208.67  E-value: 3.19e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 139 TLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYnsysRRPDSESGWMSylsei 218
Cdd:cd15987    3 SVKALYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLY----AEQDSDHCFVS----- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 219 SASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVNEN 298
Cdd:cd15987   74 TVECKAVMVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLRLHFDDTGCWDMNDN 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 299 KKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYK--YRLAKSTLLLILLMGVHEFLFTFFTDDqvqgFSR 376
Cdd:cd15987  154 TALWWVIKGPVVGSIMINFVLFIGIIIILVQKLQSPDIGGNESSiyLRLARSTLLLIPLFGIHYTVFAFSPEN----VSK 229
                        250       260
                 ....*....|....*....|....*....
gi 568976541 377 LIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15987  230 RERLVFELGLGSFQGFVVAVLYCFLNGEV 258
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
137-405 3.40e-63

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


Pssm-ID: 320401 [Multi-domain]  Cd Length: 285  Bit Score: 206.45  E-value: 3.40e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRPDS----ESGWM 212
Cdd:cd15273    1 LPIIKGISQIGYIVSLITLIIAFAIFLSFKKLHCARNKLHMHLFASFILRAFMTLLKDSLFIDGLGLLADIvernGGGNE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 213 SYLSEIS-ASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTG 291
Cdd:cd15273   81 VIANIGSnWVCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVPWIVARILFENSL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 292 CWAVNENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRA-HQMCFRDYKyRLAKSTLLLILLMGVHEFLFT--FFTD 368
Cdd:cd15273  161 CWTTNSNLLNFLIIRIPIMISVLINFILFLNIVRVLLVKLRSsVNEDSRRYK-KWAKSTLVLVPLFGVHYTIFLilSYLD 239
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 568976541 369 DQVQGFsRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15273  240 DTNEAV-ELIWLFCDQLFASFQGFFVALLYCFLNGEV 275
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
140-405 5.38e-58

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: 193.24  E-value: 5.38e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYnSYSRRPDSESGWMSYLSEIS 219
Cdd:cd15984    4 LYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLY-SGSALEEMERITEEDLKSIT 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 ----------ASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLEN 289
Cdd:cd15984   83 eappadkaqfVGCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVRATLAD 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 290 TGCWAVNE-NKKiwWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQM--CFRDYKYR-LAKSTLLLILLMGVHEFLFTF 365
Cdd:cd15984  163 TGCWDLSAgNLK--WIIQVPILAAIVVNFILFINIVRVLATKLRETNAgrCDTRQQYRkLLKSTLVLMPLFGVHYIVFMA 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 568976541 366 FTDDQVQGFSRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15984  241 MPYTEVSGILWQVQMHYEMLFNSFQGFFVAIIYCFCNGEV 280
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
140-405 1.73e-53

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


Pssm-ID: 320649 [Multi-domain]  Cd Length: 285  Bit Score: 181.27  E-value: 1.73e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYN----SYSRRPDSESGWMSYL 215
Cdd:cd15983    4 LHLMYTIGYSISLAALLVAVCILCYFKRLHCTRNYIHIHLFASFICRAGSIFVKDAVLYSgtneGEALDEKIEFGLSPGT 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 216 SEISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAV 295
Cdd:cd15983   84 RLQWVGCKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVRVSLADTQCWDL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 296 NENkKIWWIIRGPILLCVTVNFFIFLKILKLLISKF---RAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQ 372
Cdd:cd15983  164 SAG-NLKWIYQVPILAAILVNFFLFLNIVRVLASKLwetNTGKLDPRQQYRKLLKSTLVLMPLFGVHYVLFMAMPYTDVT 242
                        250       260       270
                 ....*....|....*....|....*....|...
gi 568976541 373 GFSRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15983  243 GLLWQIQMHYEMLFNSSQGFFVAFIYCFCNGEV 275
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
140-407 1.05e-52

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: 179.36  E-value: 1.05e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSRRpDSESGWMSYLSEIS 219
Cdd:cd15982    4 LYIMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAASIFVKDKVVHTHIGVK-ELDAVLMNDFQNAV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 AS----------CRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLEN 289
Cdd:cd15982   83 DAppvdksqyvgCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAAWAVVRATLAD 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 290 TGCWAVNENkKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYK--YR-LAKSTLLLILLMGVHEFLFTFF 366
Cdd:cd15982  163 ARCWELSAG-DIKWIYQAPILAAIGLNFILFLNTVRVLATKIWETNAVGYDTRkqYRkLAKSTLVLVLVFGVHYIVFVCL 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 568976541 367 TdDQVQGFSRLIRLFIQLTLSSFHGFLVALQYGFASREVPT 407
Cdd:cd15982  242 P-HTFTGLGWEIRMHCELFFNSFQGFFVSIIYCYCNGEVQT 281
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
142-405 7.14e-42

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: 149.87  E-value: 7.14e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 142 LMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLvkdmVFYNSYSRRPDSESGWMsylseisas 221
Cdd:cd15264    6 IIYYLGFSISLVALAVALIIFLYFRSLRCLRNNIHCNLIVTFILRNVTWF----IMQNTLTEIHHQSNQWV--------- 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 222 CRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPER-RLWpKYLVVGWAFPMLFVIPWIFVRASLENTGCWA-VNENK 299
Cdd:cd15264   73 CRLIVTVYNYFQVTNFFWMFVEGLYLHTMIVWAYSADKiRFW-YYIVIGWCIPCPFVLAWAIVKLLYENEHCWLpKSENS 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 300 KIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFF-TDDQVqgfSRLI 378
Cdd:cd15264  152 YYDYIYQGPILLVLLINFIFLFNIVWVLITKLRASNTLETIQYRKAVKATLVLLPLLGITYMLFFINpGDDKT---SRLV 228
                        250       260
                 ....*....|....*....|....*..
gi 568976541 379 RLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15264  229 FIYFNTFLQSFQGLFVAVFYCFLNGEV 255
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
138-405 1.43e-37

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: 138.11  E-value: 1.43e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 138 STLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYsrrpdsesgwmsylse 217
Cdd:cd13952    2 LALSIITYIGCSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLLTSSDR---------------- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 218 iSASCRSVQVLLHYFVGTNHLWLLVEGLYLH-ALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLE-------N 289
Cdd:cd13952   66 -PVLCKALAILLHYFLLASFFWMLVEAFDLYrTFVKVFGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYgpspgygG 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 290 TGCWaVNENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYR-LAKSTLLLILLMGVHeFLFTFFTd 368
Cdd:cd13952  145 EYCW-LSNGNALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSDRkQLRAYLKLFPLMGLT-WIFGILA- 221
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 568976541 369 dqVQGFSRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd13952  222 --PFVGGSLVFWYLFDILNSLQGFFIFLIFCLKNKEV 256
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
143-405 1.74e-34

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: 130.09  E-value: 1.74e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 143 MYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLvkdmVFYNSYSRRPD---SESGWmsylseis 219
Cdd:cd15260    7 VYIGGYSVSLIALIISLAIFFSFRSLRCTRITIHMNLFISFALNNLLWI----VWYKLVVDNPEvllENPIW-------- 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 asCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASL--ENTGCWAvnE 297
Cdd:cd15260   75 --CQALHVLLQYFMVCNYFWMFCEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLpdDTERCWM--E 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 298 NKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRA-------HQMcfrdykYRLAKSTLLLILLMGVHEFLFTFFTDDQ 370
Cdd:cd15260  151 ESSYQWILIVPVVLSLLINLIFLINIVRVLLTKLRAtspnpapAGL------RKAVRATLILIPLLGLQFLLIPFRPEPG 224
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 568976541 371 VQGfSRLIRLFIQLtLSSFHGFLVALQYGFASREV 405
Cdd:cd15260  225 APL-ETIYQYVSAL-LTSLQGLCVAVLFCFCNGEV 257
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
142-405 9.43e-32

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: 122.48  E-value: 9.43e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 142 LMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVfynsysrrpdsesgwMSYLSEISAS 221
Cdd:cd15263    6 TIYFIGYSLSLVALSLALWIFLYFKDLRCLRNTIHTNLMFTYILADLTWILTLTL---------------QVSIGEDQKS 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 222 CRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRA---SLENTGCWAVNEN 298
Cdd:cd15263   71 CIILVVLLHYFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYAFIGWGIPAVVIVIWAIVKAlapTAPNTALDPNGLL 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 299 KK-IW-------WIIRGPILLCVTVNFFIFLKILKLLISKFR-AHQMCFRDYkYRLAKSTLLLILLMGVhEFLFTFFTDD 369
Cdd:cd15263  151 KHcPWmaehivdWIFQGPAILVLAVNLVFLVRIMWVLITKLRsANTVETQQY-RKAAKALLVLIPLLGI-TYILVIAGPT 228
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 568976541 370 qvQGFSRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15263  229 --EGIAANIFEYVRAVLLSTQGFTVALFYCFLNTEV 262
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
146-405 1.97e-30

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: 119.11  E-value: 1.97e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 146 VGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSysrrpdsesGWMSYLSEISasCRSV 225
Cdd:cd15274   10 VGHSLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSIIIIIHLVAVVPN---------GELVARNPVS--CKIL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 226 QVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVNENkKIWWII 305
Cdd:cd15274   79 HFIHQYMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAITRAVYYNDNCWLSSET-HLLYII 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 306 RGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGfsrLIRLFIQLT 385
Cdd:cd15274  158 HGPIMAALVVNFFFLLNIVRVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQFVLFPWRPSGKILG---KIYDYVMHS 234
                        250       260
                 ....*....|....*....|
gi 568976541 386 LSSFHGFLVALQYGFASREV 405
Cdd:cd15274  235 LIHFQGFFVATIFCFCNGEV 254
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
146-405 2.14e-28

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: 113.13  E-value: 2.14e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 146 VGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYsrrpDSESGWmsylseisasCRSV 225
Cdd:cd15446   10 LGHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFLLQMIDHNIH----ESNEVW----------CRCI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 226 QVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAVNE-NKKIWWI 304
Cdd:cd15446   76 TTIYNYFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYENEQCWFGKEpGKYIDYI 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 305 IRGPILLCVTVNFFIFLKILKLLISKFRAHQMCfRDYKYRLA-KSTLLLILLMGVHEFLftFFTDDQVQGFSRLIRLFIQ 383
Cdd:cd15446  156 YQGPVILVLLINFVFLFNIVRILMTKLRASTTS-ETIQYRKAvKATLVLLPLLGITYML--FFVNPGEDDISQIVFIYFN 232
                        250       260
                 ....*....|....*....|..
gi 568976541 384 LTLSSFHGFLVALQYGFASREV 405
Cdd:cd15446  233 SFLQSFQGFFVSVFYCFLNGEV 254
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
146-405 4.42e-28

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: 112.85  E-value: 4.42e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 146 VGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALV--VLVKDMVFYNSYSRRPDSESGWMSYLSEISASCR 223
Cdd:cd15261   10 VGLCLSLVSLIISLFIFSYFRTLRNHRTRIHKNLFLAILLQVIIrlVLYIDQAITRSRGSHTNAATTEGRTINSTPILCE 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 224 SVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTG-CWAVNENKKIW 302
Cdd:cd15261   90 GFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAIVTLIKMKVNrCWFGYYLTPYY 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 303 WIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFL--FTFFTDDQVQGFSrlIRL 380
Cdd:cd15261  170 WILEGPRLAVILINLFFLLNIIRVLVSKLRESHSREIEQVRKAVKAAIVLLPLLGITNILqmIPPPLTSVIVGFA--VWS 247
                        250       260
                 ....*....|....*....|....*
gi 568976541 381 FIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15261  248 YSTHFLTSFQGFFVALIYCFLNGEV 272
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
146-405 4.93e-27

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: 109.25  E-value: 4.93e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 146 VGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSrrpDSESGWmsylseisasCRSV 225
Cdd:cd15445   10 LGHCISLVALLVAFVLFLRLRSIRCLRNIIHWNLITAFILRNATWFVVQLTMSPEVH---QSNVVW----------CRLV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 226 QVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPER-RLWpKYLVVGWAFPMLFVIPWIFVRASLENTGCWAvNENKKIW-- 302
Cdd:cd15445   77 TAAYNYFHVTNFFWMFGEGCYLHTAIVLTYSTDKlRKW-MFICIGWCIPFPIIVAWAIGKLYYDNEKCWF-GKRAGVYtd 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 303 WIIRGPILLCVTVNFFIFLKILKLLISKFRAHQMCfRDYKYRLA-KSTLLLILLMGVHEFLftFFTDDQVQGFSRLIRLF 381
Cdd:cd15445  155 YIYQGPMILVLLINFIFLFNIVRILMTKLRASTTS-ETIQYRKAvKATLVLLPLLGITYML--FFVNPGEDEISRIVFIY 231
                        250       260
                 ....*....|....*....|....
gi 568976541 382 IQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15445  232 FNSFLESFQGFFVSVFYCFLNSEV 255
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
166-405 2.91e-22

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: 95.98  E-value: 2.91e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 166 RKLHCTRNYIHMNLFASFILRA-LVVLVKDMVFYNSYsrrpdSESGWMSYLSEISASCRSVQVLLHYFVGTNHLWLLVEG 244
Cdd:cd15262   30 KRLRITRVILHRNLLISIIIRNiLVIISKVFVILDAL-----TSSGDDTVMNQNAVVCRLLSIFERAARNAVFACMFVEG 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 245 LYLHALLEPTVLPERRLWPKYlVVGWAFPMLFVIPWIFVRASLENTGCWAVnENKKIWWIIRGPILLCVTVNFFIFLKIL 324
Cdd:cd15262  105 FYLHRLIVAVFAEKSSIRFLY-VIGAVLPLFPVIIWAIIRALHNDHSCWVV-DIEGVQWVLDTPRLFILLVNTVLLVDII 182
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 325 KLLISKFRaHQMCFRDYKYRLaKSTLLLILLMGVHeFLFTFFTDDQVQGFSRLIRLFIQLTLSSFHGFLVALQYGFASRE 404
Cdd:cd15262  183 RVLVTKLR-NTEENSQTKSTT-RATLFLVPLFGLH-FVITAYRPSTDDCDWEDIYYYANYLIEGLQGFLVAILFCYINKE 259

                 .
gi 568976541 405 V 405
Cdd:cd15262  260 V 260
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
53-122 1.83e-16

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: 73.56  E-value: 1.83e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568976541   53 GVFCNGTFDKYVCWPHSFPGN-VSVPCPSYLPWWNKEspGRAYRHCLAQGTWQKQENStdtwqDESECSEN 122
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGEtVEVPCPDYFSGFDPR--GNASRNCTEDGTWSEHPPS-----NYSNCTSN 64
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
140-402 7.60e-15

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


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 74.39  E-value: 7.60e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVkdMVFYNSYSRRPDSESGWmsylseis 219
Cdd:cd14964    1 TTIILSLLTCLGLLGNLLVLLSLVRLRKRPRSTRLLLASLAACDLLASLVVLV--LFFLLGLTEASSRPQAL-------- 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 asCRSVQVLLHYFVGTNHLWLLVEGLYLHALL----EPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTG---- 291
Cdd:cd14964   71 --CYLIYLLWYGANLASIWTTLVLTYHRYFALcgplKYTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRYNtltg 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 292 --CWAVNENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFRAH---QMCFRDYKYRLAKSTLLLILLMGVHEFLFTFF 366
Cdd:cd14964  149 scYLICTTIYLTWGFLLVSFLLPLVAFLVIFSRIVLRLRRRVRAIrsaASLNTDKNLKATKSLLILVITFLLCWLPFSIV 228
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 568976541 367 TDDQVQ---GFSRLIRLFIQLTLSSFHGFLVALQYGFAS 402
Cdd:cd14964  229 FILHALvaaGQGLNLLSILANLLAVLASTLNPFIYCLGN 267
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
139-405 1.88e-13

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: 69.91  E-value: 1.88e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 139 TLQLMYTVGYSLSLISLFLALTLFLFLRKLHCT-RNYIHMNLFASFILrALVVLVKDMVFYNSYSRrpdsesgwmsylse 217
Cdd:cd15040    3 ALSIITYIGCGLSLLGLLLTIITYILFRKLRKRkPTKILLNLCLALLL-ANLLFLFGINSTDNPVL-------------- 67
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 218 isasCRSVQVLLHYFVGTNHLWLLVEGLYLH-ALLEPTVLPERRLWPKYLVVGWAFPMLFVIpwIFVRASLENTG----- 291
Cdd:cd15040   68 ----CTAVAALLHYFLLASFMWMLVEALLLYlRLVKVFGTYPRHFILKYALIGWGLPLIIVI--ITLAVDPDSYGnssgy 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 292 CWAVNENKKIWWIIrGPILLCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVhEFLFTFFTDDQV 371
Cdd:cd15040  142 CWLSNGNGLYYAFL-GPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQLRAAVSLFFLLGL-TWIFGILAIFGA 219
                        250       260       270
                 ....*....|....*....|....*....|....
gi 568976541 372 qgfsRLIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15040  220 ----RVVFQYLFAIFNSLQGFFIFIFHCLRNKEV 249
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
138-370 6.19e-13

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: 68.83  E-value: 6.19e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 138 STLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASfilralvVLVKDMVFYNSYSRrpdsesgwmsylSE 217
Cdd:cd15440    2 SALTFITYIGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLCLC-------LLIAEIVFLLGIDQ------------TE 62
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 218 ISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIpwifVRASLENTG------ 291
Cdd:cd15440   63 NRTLCGVIAGLLHYFFLAAFSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLFGYGLPALIVA----VSAGVDPTGygtedh 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 292 CWAVNENKKIWWIIrGPILLCVTVNFFIFLKILKLLIS-KFRAHQMCFRDYKYRLA---KSTLLLILLMGVhEFLFTFFT 367
Cdd:cd15440  139 CWLSTENGFIWSFV-GPVIVVLLANLVFLGMAIYVMCRhSSRSASKKDASKLKNIRgwlKGSIVLVVLLGL-TWTFGLLF 216

                 ...
gi 568976541 368 DDQ 370
Cdd:cd15440  217 INQ 219
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
140-335 2.30e-12

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: 66.97  E-value: 2.30e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNsysrrpdsesgwmsylseiS 219
Cdd:cd15933    4 LSIISYIGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGN-------------------K 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 ASCRSVQVLLHYFVGTNHLWLLVEGLYLHaLLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASL--ENTGCWAVNE 297
Cdd:cd15933   65 VACKVVAILLHFFFMAAFSWMLVEGLHLY-LMIVKVFNYKSKMRYYYFIGWGLPAIIVAISLAILFDDygSPNVCWLSLD 143
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 568976541 298 NKKIWWIIrGPILLCVTVNFFIFLKILKLLISKFRAHQ 335
Cdd:cd15933  144 DGLIWAFV-GPVIFIITVNTVILILVVKITVSLSTNDA 180
HormR smart00008
Domain present in hormone receptors;
52-122 2.41e-12

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 62.15  E-value: 2.41e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568976541    52 SGVFCNGTFDKYVCWPHSFPGN-VSVPCPSYLPWWNKEspGRAYRHCLAQGTWqkqensTDTWQDESECSEN 122
Cdd:smart00008   1 TDLGCPATWDGIICWPQTPAGQlVEVPCPKYFSGFSYK--TGASRNCTENGGW------SPPFPNYSNCTSN 64
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
172-405 3.07e-09

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: 57.63  E-value: 3.07e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 172 RNYIHMNLfasfilrALVVLVKDMVFYNSYSRRPDSesgwmsylseisASCRSVQVLLHYFVGTNHLWLLVEGLYLHALL 251
Cdd:cd15256   39 RYHIHANL-------SFAVLVAQILLLISFRFEPGT------------LPCKIMAILLHFFFLSAFAWMLVEGLHLYSMV 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 252 EPTVLPERRLWPKYLVVGWAFPMLFVIpwIFVRASL----ENTGCWAVNENKKIWWIIrGPILLCVTVNFFIFLKILKlL 327
Cdd:cd15256  100 IKVFGSEESKHFYYYGIGWGSPLLICI--ISLTSALdsygESDNCWLSLENGAIWAFV-APALFVIVVNIGILIAVTR-V 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 328 ISKFRAHqmcfrDYK-------YRL-AKSTLLLILLMGVHEFLFTFFTDDQVqgfsrLIRLFIQLTLSSFHGFLVALQYG 399
Cdd:cd15256  176 ISRISAD-----NYKvhgdanaFKLtAKAVAVLLPILGSSWVFGVLAVNTHA-----LVFQYMFAIFNSLQGFFIFLFHC 245

                 ....*.
gi 568976541 400 FASREV 405
Cdd:cd15256  246 LLNSEV 251
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
140-398 2.64e-08

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: 54.73  E-value: 2.64e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLhcTRNY---IHMNLFASFILRALVVLVkdmvfynsysrrpdseSGWMSyLS 216
Cdd:cd15258    4 LTFISYVGCGISAIFLAITILTYIAFRKL--RRDYpskIHMNLCAALLLLNLAFLL----------------SSWIA-SF 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 217 EISASCRSVQVLLHYFVGTNHLWLLVEGLYLH-ALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLENTGCWAV 295
Cdd:cd15258   65 GSDGLCIAVAVALHYFLLACLTWMGLEAFHLYlLLVKVFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPITIPN 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 296 NENKK---IWWiIRGPILLCVTV----------NFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVhEFL 362
Cdd:cd15258  145 GEGFQndsFCW-IRDPVVFYITVvgyfgltflfNMVMLATVLVQICRLREKAQATPRKRALHDLLTLLGLTFLLGL-TWG 222
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 568976541 363 FTFFTddqvQGFSRLIRLFIQLTLSSFHGFLVALQY 398
Cdd:cd15258  223 LAFFA----WGPFNLPFLYLFAIFNSLQGFFIFIWY 254
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
140-405 3.78e-08

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: 54.47  E-value: 3.78e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSrrpdsesgwmsylseis 219
Cdd:cd15991    4 LKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIGINQTENPFV----------------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 asCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMlfVIPWIFVRASLENTG----CWAV 295
Cdd:cd15991   67 --CTVVAILLHYFYMSTFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPA--IITGLAVGLDPQGYGnpdfCWLS 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 296 NENKKIwWIIRGPILLCVTVNFFIFlkILKLLISKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVQGFS 375
Cdd:cd15991  143 VQDTLI-WSFAGPIGIVVIINTVIF--VLAAKASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGLMAVNSDTLSFH 219
                        250       260       270
                 ....*....|....*....|....*....|
gi 568976541 376 RLIRLFiqltlSSFHGFLVALQYGFASREV 405
Cdd:cd15991  220 YLFAIF-----SCLQGIFIFFFHCIFNKEV 244
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
139-331 7.46e-08

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: 53.61  E-value: 7.46e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 139 TLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKdmvfynsySRRPDSESGwmsylsei 218
Cdd:cd15438    3 PLTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLG--------INNTNNQVA-------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 219 sasCRSVQVLLHYFVGTNHLWLLVEGLYLHaLLEPTVLPERRLWPKYLV-VGWAFPMLFVIpwifVRASLENTG------ 291
Cdd:cd15438   67 ---CAVVAGLLHYFFLAAFCWMSLEGVELY-LMVVQVFNTQSLKKRYLLlIGYGVPLVIVA----ISAAVNSKGygtqrh 138
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568976541 292 CWAVNENKKIWWIIrGPILLCVTVNFFIFLKILKLLISKF 331
Cdd:cd15438  139 CWLSLERGFLWSFL-GPVCLIILVNAIIFVITVWKLAEKF 177
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
139-356 5.02e-07

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: 50.71  E-value: 5.02e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 139 TLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLfasfilrALVVLVKDMVFYNSYSRRpdsesgwmsylsEI 218
Cdd:cd15441    3 LLKIVTYIGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNL-------VACLLLAELLFLLGINQT------------EN 63
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 219 SASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASL--ENTGCWAVN 296
Cdd:cd15441   64 LFPCKLIAILLHYFYLSAFSWLLVESLHLYRMLTEPRDINHGHMRFYYLLGYGIPAIIVGLSVGLRPDGygNPDFCWLSV 143
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568976541 297 ENKKIWWIIrGPILLCVTVNFFIFlkILKLLISKFRA-HQMCFRDYKYRLAKSTLLLILLM 356
Cdd:cd15441  144 NETLIWSFA-GPIAFVIVITLIIF--ILALRASCTLKrHVLEKASVRTDLRSSFLLLPLLG 201
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
140-328 1.53e-06

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: 49.54  E-value: 1.53e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVkdmvfynsysrrpdsesGWMSYLSEIS 219
Cdd:cd16007    4 LSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLI-----------------GIDKTQYQIA 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 asCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFV--IPWIFVRASLENTGCWAVNE 297
Cdd:cd16007   67 --CPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVEVFESEYSRKKYYYLCGYCFPALVVgiSAAIDYRSYGTEKACWLRVD 144
                        170       180       190
                 ....*....|....*....|....*....|.
gi 568976541 298 NKKIWWIIrGPILLCVTVNFFIFLKILKLLI 328
Cdd:cd16007  145 NYFIWSFI-GPVSFVIVVNLVFLMVTLHKMI 174
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
222-332 2.37e-06

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: 49.08  E-value: 2.37e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 222 CRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMlfVIPWIFVRASLEN----TGCWaVNE 297
Cdd:cd15255   67 CWAVTALLHLFFLAAFSWMLVEGLLLWSKVVAVNMSEDRRMKFYYVTGWGLPV--VIVAVTLATSFNKyvadQHCW-LNV 143
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568976541 298 NKKIWWIIRGPILLCVTVNFFIFLKILKLLISKFR 332
Cdd:cd15255  144 QTDIIWAFVGPVLFVLTVNTFVLFRVVMVTVSSAR 178
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
140-405 1.82e-05

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: 46.35  E-value: 1.82e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKdmvfynsysrrpdsesgwmSYLSEIS 219
Cdd:cd15252    4 LTRITQVGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFLAELVFLIG-------------------INTTTNK 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 ASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVI--PWIFVRASLENTGCWAVNE 297
Cdd:cd15252   65 IFCSVIAGLLHYFFLAAFAWMFIEGIQLYLMLVEVFENEGSRHKNFYIFGYGSPAVIVGvsAALGYRYYGTTKVCWLSTE 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 298 NKKIWWIIrGPILLCVTVNFFIFLKILKLLI---SKFRAHQMCFRDYKYRLAKSTLLLILLMGVHEFLFTFFTDDQVqgf 374
Cdd:cd15252  145 NYFIWSFI-GPATLIILLNLIFLGVAIYKMFrhtAGLKPEVSCLENIRSWARGAIALLFLLGLTWIFGVLHINHASV--- 220
                        250       260       270
                 ....*....|....*....|....*....|.
gi 568976541 375 srlIRLFIQLTLSSFHGFLVALQYGFASREV 405
Cdd:cd15252  221 ---VMAYLFTVSNSLQGMFIFLFHCVLSRKV 248
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
146-323 2.48e-05

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: 45.94  E-value: 2.48e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 146 VGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKdmvfynsysrrpdsesgwmSYLSEISASCRSV 225
Cdd:cd15436   10 VGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFIAELLFLIG-------------------INRTQYTIACPIF 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 226 QVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFV--IPWIFVRASLENTGCWAVNENKKIWW 303
Cdd:cd15436   71 AGLLHFFFLAAFCWLCLEGVQLYLLLVEVFESEYSRRKYFYLCGYSFPALVVavSAAIDYRSYGTEKACWLRVDNYFIWS 150
                        170       180
                 ....*....|....*....|
gi 568976541 304 IIrGPILLCVTVNfFIFLKI 323
Cdd:cd15436  151 FI-GPVTFVITLN-LVFLVI 168
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
222-329 3.65e-05

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: 45.22  E-value: 3.65e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 222 CRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMlfVIPWIFVRASLENTG----CWaVNE 297
Cdd:cd15993   67 CTVVAILLHYFFLSTFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPA--IITGLAVGLDPEGYGnpdfCW-ISI 143
                         90       100       110
                 ....*....|....*....|....*....|..
gi 568976541 298 NKKIWWIIRGPILLCVTVNFFIFLKILKLLIS 329
Cdd:cd15993  144 HDKLVWSFAGPIVVVIVMNGVMFLLVARMSCS 175
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
140-332 2.24e-04

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: 42.98  E-value: 2.24e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVK-DMvfynsysrrpdsesgwmsylSEI 218
Cdd:cd16006    4 LTVITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIGiDK--------------------TEY 63
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 219 SASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFP--MLFVIPWIFVRASLENTGCWAVN 296
Cdd:cd16006   64 KIACPIFAGLLHFFFLAAFAWMCLEGVQLYLMLVEVFESEYSRKKYYYVAGYLFPatVVGVSAAIDYKSYGTEKACWLRV 143
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 568976541 297 ENKKIWWIIrGPillcvtVNFFIFLKILKLLISKFR 332
Cdd:cd16006  144 DNYFIWSFI-GP------VTFIILLNLIFLVITLCK 172
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
138-358 3.62e-04

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: 42.17  E-value: 3.62e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 138 STLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLVKDMVFYNSYSrrpdsesgwmsylse 217
Cdd:cd15437    2 NVLTRITQLGIIISLICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELIFLIGINMNANKLF--------------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 218 isasCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYLVVGWAFPMLFVipwiFVRASL------ENTG 291
Cdd:cd15437   67 ----CSIIAGLLHYFFLAAFAWMCIEGIHLYLIVVGVIYNKGFLHKNFYIFGYGSPAVVV----GISAALgykyygTTKV 138
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 292 CWAVNENKKIWWIIrGPILLCVTVNFFIFLKILKLLI---SKFRAHQMCFRDYKyRLAKSTLLLILLMGV 358
Cdd:cd15437  139 CWLSTENNFIWSFI-GPACLIILVNLLAFGVIIYKVFrhtAMLKPEVSCYENIR-SCARGALALLFLLGA 206
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
139-411 5.16e-04

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: 42.17  E-value: 5.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 139 TLQLMYTVGYSLSLISLFLALTLFLFLRKLHCTR-NYIHMNLFASFILRALVVLV------KDMVFYNSYSRRPDSESGW 211
Cdd:cd15257    3 TLDIISTIGCVLSIAGLVITIIFHLHTRKLRKSSvTWVLLNLCSSLLLFNIIFTSgventnNDYEISTVPDRETNTVLLS 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 212 MSYLSEISASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTVLPERRLWPKYL-VVGWAFPMlfVIPWIFVRASLENT 290
Cdd:cd15257   83 EEYVEPDTDVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQAsAIGWGIPA--VVVAITLGATYRFP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 291 GCWAVNE----NKKIWWI--------IRGPIL--------LCVTVNFFIFLKILKLLISKFRAHQMCFRDYKYRLAKSTL 350
Cdd:cd15257  161 TSLPVFTrtyrQEEFCWLaaldknfdIKKPLLwgfllpvgLILITNVILFIMTSQKVLKKNNKKLTTKKRSYMKKIYITV 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568976541 351 LLILLMGVHEFL--FTFFTDDQvqgfSRLIRLFIQLTLSSFHGFLVALQYGFASREVPTFASS 411
Cdd:cd15257  241 SVAVVFGITWILgyLMLVNNDL----SKLVFSYIFCITNTTQGVQIFILYTWRTPEFRKLVSK 299
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
137-286 1.75e-03

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: 40.12  E-value: 1.75e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 137 LSTLQLMYTVGYSLSLISLFLALTLFLFLRKL-HCTRNYIHMNLFAS-FILRALVVLVKDMVFYNSysrrpdsesgwmsy 214
Cdd:cd15443    1 LEPLTYISIVGCSISAAASLLTILLHFFSRKQpKDSTTRIHMNLLGSlFLLNGSFLLSPPLATSQS-------------- 66
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568976541 215 lseiSASCRSVQVLLHYFVGTNHLWLLVEGLYLHALLEPTV-LPERRLWPKYLVVGWAFPMLFVIPWIFVRAS 286
Cdd:cd15443   67 ----TWLCRAAAALLHYSLLCCLTWMAIEGFHLYLLLVKVYnIYIRRYVLKLCVLGWGLPALIVLLVLIFKRE 135
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
210-277 5.73e-03

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: 38.72  E-value: 5.73e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568976541 210 GWMSYLsEISASCRSVQVLLHYFVGTNHLWLLVEGLYLH-ALLEPTVLPERRLWPKYLVVGWAFPMLFV 277
Cdd:cd15996   59 GWIASF-EIDELCITVAVLLHFFLLATFTWMGLEAIHMYiALVKVFNTYIRRYILKFCIIGWGLPALIV 126
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
211-328 7.47e-03

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: 38.27  E-value: 7.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 211 WMSYLSEISASCRSVQVLLHYFVGTNHLWLLVEGLYLH-ALLEPTVLPERRLWPKYLVVGWAFPMLFVIPWIFVRASLEN 289
Cdd:cd15444   60 WIALYKDIVGLCISVAVFLHYFLLVSFTWMGLEAFHMYlALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYG 139
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 568976541 290 TGCWAVNEN---KKIWWIIRGPILLCVTVNFF--IFLKILKLLI 328
Cdd:cd15444  140 LGSYGKSPNgstDDFCWINNNIVFYITVVGYFcvIFLLNISMFI 183
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
140-331 9.55e-03

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: 37.88  E-value: 9.55e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 140 LQLMYTVGYSLSLISLFLALTLFLFLRKLHCTRNYIHMNLFASFILRALVVLvkdmvfynsysrrpdsesgWMSYLSEIS 219
Cdd:cd15931    4 LEWINRVGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSMSHTLFL-------------------AGIEYVENE 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976541 220 ASCRSVQVLLHYFVGTNHLWLLVEGLYLHALL----EPTVLPERRLWPKYL-VVGWAFPMLFVIpwifVRASLENTG--- 291
Cdd:cd15931   65 LACTVMAGLLHYLFLASFVWMLLEALQLHLLVrrltKVQVIQRDGLPRPLLcLIGYGVPFLIVG----VSALVYSDGyge 140
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 568976541 292 ---CWaVNENKKIWWIIRGPILLCVTVNFFIFLKILKLLISKF 331
Cdd:cd15931  141 akmCW-LSQERGFNWSFLGPVIAIIGINWILFCATLWCLRQTL 182
 
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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