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Conserved domains on  [gi|672070171|ref|XP_008766690|]
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glucagon receptor isoform X1 [Rattus norvegicus]

Protein Classification

hormone receptor( domain architecture ID 12039861)

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
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
142-423 1.72e-155

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: 443.11  E-value: 1.72e-155
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 142 KMYSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLSvSVW 221
Cdd:cd15267    1 KTYSSFQVMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASSVLVIDGLLRTRYSQKIEDDLS-STW 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 222 LSDGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCW 301
Cdd:cd15267   80 LSDEAVAGCRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPALFVVPWVVVKCLYENVQCW 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 302 TSNDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQG 381
Cdd:cd15267  160 TSNDNMGFWWILRFPVFLAILINFFIFVRIIQILVSKLRARQMHYTDYKFRLAKSTLTLIPLLGIHEVVFAFVTDEHAQG 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 672070171 382 TLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15267  240 TLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHR 281
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
61-128 8.30e-20

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: 83.19  E-value: 8.30e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672070171   61 ELVCNRTFDKYSCWPDTPPNTTANISCPWYLPWYHKVQHrlVFKRCGPDGQWVRGPRgqswRDASQCQ 128
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDPRGN--ASRNCTEDGTWSEHPP----SNYSNCT 62
 
Name Accession Description Interval E-value
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
142-423 1.72e-155

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: 443.11  E-value: 1.72e-155
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 142 KMYSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLSvSVW 221
Cdd:cd15267    1 KTYSSFQVMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASSVLVIDGLLRTRYSQKIEDDLS-STW 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 222 LSDGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCW 301
Cdd:cd15267   80 LSDEAVAGCRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPALFVVPWVVVKCLYENVQCW 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 302 TSNDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQG 381
Cdd:cd15267  160 TSNDNMGFWWILRFPVFLAILINFFIFVRIIQILVSKLRARQMHYTDYKFRLAKSTLTLIPLLGIHEVVFAFVTDEHAQG 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 672070171 382 TLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15267  240 TLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHR 281
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
144-377 6.49e-78

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: 243.73  E-value: 6.49e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171  144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTrysqkiGDDLSVSVWLs 223
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFN------KQDLDHCSWV- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171  224 dgavaGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVV--KCLFENVQCW 301
Cdd:pfam00002  74 -----GCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCW 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171  302 TSNDNmGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYK--FRLARSTLTLIPLLGVHEV--VFAFVTDE 377
Cdd:pfam00002 149 LSNEN-GLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKqyRRLAKSTLLLLPLLGITWVfgLFAFNPEN 227
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
61-128 8.30e-20

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: 83.19  E-value: 8.30e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672070171   61 ELVCNRTFDKYSCWPDTPPNTTANISCPWYLPWYHKVQHrlVFKRCGPDGQWVRGPRgqswRDASQCQ 128
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDPRGN--ASRNCTEDGTWSEHPP----SNYSNCT 62
HormR smart00008
Domain present in hormone receptors;
60-135 2.11e-19

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 82.18  E-value: 2.11e-19
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 672070171    60 SELVCNRTFDKYSCWPDTPPNTTANISCPWYLPWYHKVQHrlVFKRCGPDGQWvrgprGQSWRDASQCQMDDDEIE 135
Cdd:smart00008   1 TDLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTG--ASRNCTENGGW-----SPPFPNYSNCTSNDYEEL 69
 
Name Accession Description Interval E-value
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
142-423 1.72e-155

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: 443.11  E-value: 1.72e-155
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 142 KMYSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLSvSVW 221
Cdd:cd15267    1 KTYSSFQVMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASSVLVIDGLLRTRYSQKIEDDLS-STW 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 222 LSDGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCW 301
Cdd:cd15267   80 LSDEAVAGCRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPALFVVPWVVVKCLYENVQCW 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 302 TSNDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQG 381
Cdd:cd15267  160 TSNDNMGFWWILRFPVFLAILINFFIFVRIIQILVSKLRARQMHYTDYKFRLAKSTLTLIPLLGIHEVVFAFVTDEHAQG 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 672070171 382 TLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15267  240 TLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHR 281
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
144-423 8.88e-151

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: 431.09  E-value: 8.88e-151
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLsVSVWLS 223
Cdd:cd15929    1 LSSLQVMYTVGYSLSLAALVLALAILLGLRKLHCTRNYIHANLFASFILRALSVLVKDALLPRRYSQKGDQDL-WSTLLS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 224 DGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTS 303
Cdd:cd15929   80 NQASLGCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLLLGWGAPVLFVVPWGIVKYLYENTGCWTR 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 304 NDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQGTL 383
Cdd:cd15929  160 NDNMAYWWIIRLPILLAILINFFIFVRILKILVSKLRANQMCKTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEQARGTL 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 672070171 384 RSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15929  240 RFIKLFFELFLSSFQGLLVAVLYCFANKEVQSELRKKWHR 279
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
146-422 1.36e-113

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: 336.52  E-value: 1.36e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 146 SYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLSVSVWLSDG 225
Cdd:cd15985    3 SFRMLYTVGYTLSLLTLVSALLILTSIRKLHCTRNYIHANLFASFILRAVSVIVKDTLLERRWGREIMRVADWGELLSHK 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 226 AVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSND 305
Cdd:cd15985   83 AAIGCRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVLFVVPWMLAKYLKENKECWALNE 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 306 NMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQGTLRS 385
Cdd:cd15985  163 NMAYWWIIRIPILLASLINLLIFMRILKVILSKLRANQKGYADYKLRLAKATLTLIPLFGIHEVVFIFATDEQTTGILRY 242
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 672070171 386 TKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWR 422
Cdd:cd15985  243 IKVFFTLFLNSFQGFLVAVLYCFANKEVKSELLKKWR 279
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
145-423 3.22e-110

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: 327.86  E-value: 3.22e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 145 SSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLSVSVWLSD 224
Cdd:cd15266    2 LTLQLIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDIVLYSTYSKRPDDETGWISYLSE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 225 GAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSN 304
Cdd:cd15266   82 ESSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVVPWGVAKILLENTGCWGRN 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 305 DNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQGTLR 384
Cdd:cd15266  162 ENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYKYRLARSTLVLIPLLGIHEVVFSFITDEQVEGFSR 241
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 672070171 385 STKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15266  242 HIRLFIQLTLSSFQGFLVAVLYCFANGEVKAELKKRWQL 280
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
149-423 3.58e-99

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: 299.56  E-value: 3.58e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 149 VMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVID----WLLKTRYSQKIGDDLsvsvwLSD 224
Cdd:cd15268    6 IIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDaalkWMYSTAAQQHQWDGL-----LSY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 225 GAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSN 304
Cdd:cd15268   81 QDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFVIPWGIVKYLYEDEGCWTRN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 305 DNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQGTLR 384
Cdd:cd15268  161 SNMNYWLIIRLPILFAIGVNFLIFIRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLR 240
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 672070171 385 STKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15268  241 FVKLFTELSFTSFQGLMVAILYCFVNNEVQMEFRKSWER 279
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
173-423 3.03e-89

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: 273.72  E-value: 3.03e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDlsvsvWLSDGAVAGCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15041   30 RSLRCTRIRLHINLFLSFILRAVFWIIWDLLVVYDRLTSSGVE-----TVLMQNPVGCKLLSVLKRYFKSANYFWMLCEG 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSNDNMGFWWILRIPVLLAILINFFIFVRII 332
Cdd:cd15041  105 LYLHRLIVVAFFSEPSSLKLYYAIGWGLPLVIVVIWAIVRALLSNESCWISYNNGHYEWILYGPNLLALLVNLFFLINIL 184
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 333 HLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAqgTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKE 412
Cdd:cd15041  185 RILLTKLRSHPNAEPSNYRKAVKATLILIPLFGIQYLLTIYRPPDGS--EGELVYEYFNAILNSSQGFFVAVIYCFLNGE 262
                        250
                 ....*....|.
gi 672070171 413 VQAELLRRWRR 423
Cdd:cd15041  263 VQSELKRKWSR 273
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
148-423 5.94e-85

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: 262.75  E-value: 5.94e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 148 QVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTrysqkigddlSVSVWLSDGAV 227
Cdd:cd15275    5 KTMYTVGYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFIKDAVLFS----------SEDDNHCDIYT 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 228 AGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSNDNM 307
Cdd:cd15275   75 VGCKVAMVFSNYCIMANYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFIISWAIARYLHENEGCWDTRRNA 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 308 GFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYAD---YKfRLARSTLTLIPLLGVHEVVFAFVTDEHAQGTLR 384
Cdd:cd15275  155 WIWWIIRGPVILSIFVNFILFLNILRILMRKLRAPDMRGNEfsqYK-RLAKSTLLLIPLFGLHYILFAFFPEDVSSGTME 233
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 672070171 385 sTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15275  234 -IWLFFELALGSFQGFVVAVLYCFLNGEVQLEIQRKWRR 271
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
144-423 1.49e-82

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: 256.59  E-value: 1.49e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLktrYSQKIGDDLSVSVwls 223
Cdd:cd15930    1 YLTVKIIYTVGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKDAVL---FSSEDVDHCFVST--- 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 224 dgavAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTS 303
Cdd:cd15930   75 ----VGCKASMVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVWIVARLYFEDTGCWDI 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 304 NDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYAD---YKfRLARSTLTLIPLLGVHEVVFAFVTDEHAQ 380
Cdd:cd15930  151 NDESPYWWIIKGPILISILVNFVLFINIIRILLQKLRSPDIGGNEssqYK-RLARSTLLLIPLFGIHYIVFAFFPENISL 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 672070171 381 GtlrsTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15930  230 G----IRLYFELCLGSFQGFVVAVLYCFLNGEVQAEIKRKWRS 268
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
144-377 6.49e-78

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: 243.73  E-value: 6.49e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171  144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTrysqkiGDDLSVSVWLs 223
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFN------KQDLDHCSWV- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171  224 dgavaGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVV--KCLFENVQCW 301
Cdd:pfam00002  74 -----GCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCW 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171  302 TSNDNmGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYK--FRLARSTLTLIPLLGVHEV--VFAFVTDE 377
Cdd:pfam00002 149 LSNEN-GLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKqyRRLAKSTLLLLPLLGITWVfgLFAFNPEN 227
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
149-423 2.12e-75

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: 238.83  E-value: 2.12e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 149 VMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLktrySQKIG-------DDLSVSVW 221
Cdd:cd15272    6 LMYNIGYGLSLVSLLIAVIIMLYFKKLHCPRNTIHINLFVSFILRAVLSFIKENLL----VQGVGfpgdvyyDSNGVIEF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 222 LSDGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCW 301
Cdd:cd15272   82 KDEGSHWECKLFFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLLFVLPWVFVRATLEDTLCW 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 302 TSNDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADyKFR---LARSTLTLIPLLGVHEVVFAFVTDEH 378
Cdd:cd15272  162 NTNTNKGYFWIIRGPIVISIAINFLFFINIVRVLFTKLKASNTQESR-PFRyrkLAKSTLVLIPLFGVHYMVFVVLPDSM 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 672070171 379 AQGTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15272  241 SSDEAELVWLYFEMFFNSFQGFIVALLFCFLNGEVQSEIKKKWQR 285
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
144-423 3.33e-74

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: 235.13  E-value: 3.33e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLktrYSQKIGDDLSVsvwls 223
Cdd:cd15269    1 FGTVKTGYTIGHSLSLISLTAAMIILCLFRKLHCTRNYIHMHLFMSFILRAIAVFIKDAVL---FESGEEDHCSV----- 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 224 dgAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTS 303
Cdd:cd15269   73 --ASVGCKAAMVFFQYCIMANFFWLLVEGLYLHTLLAVSFFSERKYFWWYILIGWGAPSVFITAWSVARIYFEDVGCWDT 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 304 NDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYK--FRLARSTLTLIPLLGVHEVVFAFVTDEHAQg 381
Cdd:cd15269  151 IIESLLWWIIKTPILVSILVNFILFICIIRILVQKLHSPDIGRNESSqySRLAKSTLLLIPLFGIHYIMFAFFPDNFKA- 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 672070171 382 tlrSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15269  230 ---EVKLVFELILGSFQGFVVAVLYCFLNGEVQAELKRKWRR 268
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
144-422 4.27e-74

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: 234.70  E-value: 4.27e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDlsvsvwls 223
Cdd:cd15986    1 YIVVKTIYTLGHSVSLIALTTGSTILCLFRKLHCTRNYIHLNLFFSFILRAISVLVKDDILYSSSNTEHCTV-------- 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 224 DGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLsITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTS 303
Cdd:cd15986   73 PPSLIGCKVSLVILQYCIMANFYWLLVEGLYLHTLL-VVIFSENRHFIVYLLIGWGIPTVFIIAWIVARIYLEDTGCWDT 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 304 NDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYAD---YKfRLARSTLTLIPLLGVHEVVFAFVTDehaq 380
Cdd:cd15986  152 NDHSVPWWVIRIPIIISIILNFILFISIIRILLQKLRSPDVGGNDqsqYK-RLAKSTLLLIPLFGVHYIVFVYFPD---- 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 672070171 381 GTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWR 422
Cdd:cd15986  227 SSSSNYQIFFELCLGSFQGLVVAILYCFLNSEVQGELKRKWR 268
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
144-423 9.02e-74

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: 233.85  E-value: 9.02e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLktrYSQKIGDDLSVSVwls 223
Cdd:cd15271    1 FSTVKLLYTVGYGTSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALAVFIKDAVL---FADESVDHCTMST--- 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 224 dgavAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWtS 303
Cdd:cd15271   75 ----VACKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVWVLTRLQYDNRGCW-D 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 304 NDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKF--RLARSTLTLIPLLGVHEVVFAFVTdEHAQG 381
Cdd:cd15271  150 DLESRIWWIIKTPILLSVFVNFLIFINVIRILVQKLKSPDVGGNDTSHymRLAKSTLLLIPLFGVHYVVFAFFP-EHVGV 228
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 672070171 382 TLRstkLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15271  229 EAR---LYFELVLGSFQGFIVALLYCFLNGEVQAEIKKRLGK 267
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
148-423 1.31e-73

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: 234.19  E-value: 1.31e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 148 QVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLSVSVWLSDGAV 227
Cdd:cd15265    5 YLIYTVGYSISLVSLTVAVFILGYFRRLHCTRNYIHMHLFVSFMLRAVSIFVKDAVLYSGSGLDELERPSMEDLKSIVEA 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 228 --------AGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQ 299
Cdd:cd15265   85 ppvdksqyVGCKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVFVIPWASVRATLADTR 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 300 CW-TSNDNMgfWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYAD----YKfRLARSTLTLIPLLGVHEVVFAFV 374
Cdd:cd15265  165 CWdLSAGNY--KWIYQVPILAAIVVNFILFLNIVRVLATKLRETNAGRCDtrqqYR-KLAKSTLVLIPLFGVHYIVFMGM 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 672070171 375 TDEHAqGTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15265  242 PYTEV-GLLWQIRMHYELFFNSFQGFFVAIIYCFCNGEVQAEIKKRWER 289
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
144-422 9.33e-69

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: 221.00  E-value: 9.33e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLktrYSQKIGDDLSVSVwls 223
Cdd:cd15987    1 YLSVKALYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVL---YAEQDSDHCFVST--- 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 224 dgavAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTS 303
Cdd:cd15987   75 ----VECKAVMVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLRLHFDDTGCWDM 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 304 NDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQM--HYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAqg 381
Cdd:cd15987  151 NDNTALWWVIKGPVVGSIMINFVLFIGIIIILVQKLQSPDIggNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVS-- 228
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 672070171 382 tlRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWR 422
Cdd:cd15987  229 --KRERLVFELGLGSFQGFVVAVLYCFLNGEVQSEIKRKWR 267
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
173-423 2.60e-68

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: 220.32  E-value: 2.60e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLVIDWL----LKTRYSQKIGDDLSVSVWLSDGAVAGCRVATVIMQYGIIANYCWL 248
Cdd:cd15273   30 KKLHCARNKLHMHLFASFILRAFMTLLKDSLfidgLGLLADIVERNGGGNEVIANIGSNWVCKAITSLWQYFIIANYSWI 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 249 LVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSNDNMGFWWILRIPVLLAILINFFIF 328
Cdd:cd15273  110 LMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVPWIVARILFENSLCWTTNSNLLNFLIIRIPIMISVLINFILF 189
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 329 VRIIHLLVAKLRA-HQMHYADYKfRLARSTLTLIPLLGVHEVVF---AFVTDEHAqgTLRSTKLFFDLFFSSFQGLLVAV 404
Cdd:cd15273  190 LNIVRVLLVKLRSsVNEDSRRYK-KWAKSTLVLVPLFGVHYTIFlilSYLDDTNE--AVELIWLFCDQLFASFQGFFVAL 266
                        250
                 ....*....|....*....
gi 672070171 405 LYCFLNKEVQAELLRRWRR 423
Cdd:cd15273  267 LYCFLNGEVRAEIQRKWRR 285
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
144-423 6.37e-65

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: 210.81  E-value: 6.37e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 144 YSSYQVMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLktrYSQKIGDDLSVSVwls 223
Cdd:cd15270    1 FSTVKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFIKDAAL---FQEDDTDHCSMST--- 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 224 dgavAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTS 303
Cdd:cd15270   75 ----VLCKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCKLYFEDTECWDI 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 304 NDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKL--RAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQG 381
Cdd:cd15270  151 NNDSPYWWIIKGPIVISVGVNFLLFLNIIRILLKKLdpRQINFNNSAQYRRLSKSTLLLIPLFGTHYIIFNFLPDYAGLG 230
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 672070171 382 tlrsTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15270  231 ----IRLYLELCLGSFQGFIVAVLYCFLNQEVQTEISRKWYG 268
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
149-423 2.83e-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: 194.40  E-value: 2.83e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 149 VMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLSVSVWLS----- 223
Cdd:cd15984    6 LIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGSALEEMERITEEDLKSiteap 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 224 ---DGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQC 300
Cdd:cd15984   86 padKAQFVGCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVRATLADTGC 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 301 WT-SNDNMGfwWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYK---FRLARSTLTLIPLLGVHEVVFAFVTD 376
Cdd:cd15984  166 WDlSAGNLK--WIIQVPILAAIVVNFILFINIVRVLATKLRETNAGRCDTRqqyRKLLKSTLVLMPLFGVHYIVFMAMPY 243
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 672070171 377 EHAQGTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15984  244 TEVSGILWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 290
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
149-423 3.51e-55

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: 186.28  E-value: 3.51e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 149 VMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGDDLSVSVWLSDGA-- 226
Cdd:cd15983    6 LMYTIGYSISLAALLVAVCILCYFKRLHCTRNYIHIHLFASFICRAGSIFVKDAVLYSGTNEGEALDEKIEFGLSPGTrl 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 227 -VAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWT-SN 304
Cdd:cd15983   86 qWVGCKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVRVSLADTQCWDlSA 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 305 DNMGfwWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYAD----YKfRLARSTLTLIPLLGVHEVVFAFVTDEHAQ 380
Cdd:cd15983  166 GNLK--WIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKLDprqqYR-KLLKSTLVLMPLFGVHYVLFMAMPYTDVT 242
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 672070171 381 GTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15983  243 GLLWQIQMHYEMLFNSSQGFFVAFIYCFCNGEVQAEIKKAWLR 285
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
149-423 4.55e-51

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: 175.51  E-value: 4.55e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 149 VMYTVGYSLSLGALLLALVILLGLRKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKIGD--------DLSVSV 220
Cdd:cd15982    6 IMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAASIFVKDKVVHTHIGVKELDavlmndfqNAVDAP 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 221 WLSDGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQC 300
Cdd:cd15982   86 PVDKSQYVGCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAAWAVVRATLADARC 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 301 WT-SNDNMGfwWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYK---FRLARSTLTLIPLLGVHEVVfaFVTD 376
Cdd:cd15982  166 WElSAGDIK--WIYQAPILAAIGLNFILFLNTVRVLATKIWETNAVGYDTRkqyRKLAKSTLVLVLVFGVHYIV--FVCL 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 672070171 377 EHA-QGTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15982  242 PHTfTGLGWEIRMHCELFFNSFQGFFVSIIYCYCNGEVQTEIKKTWTR 289
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
173-423 6.24e-45

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: 158.35  E-value: 6.24e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSQKigddlsvSVWLsdgavagCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15264   30 RSLRCLRNNIHCNLIVTFILRNVTWFIMQNTLTEIHHQS-------NQWV-------CRLIVTVYNYFQVTNFFWMFVEG 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCW-TSNDNMGFWWILRIPVLLAILINFFIFVRI 331
Cdd:cd15264   96 LYLHTMIVWAYSADKIRFWYYIVIGWCIPCPFVLAWAIVKLLYENEHCWlPKSENSYYDYIYQGPILLVLLINFIFLFNI 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 332 IHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVF---------AFVTDEHAQGTLRSTklffdlffssfQGLLV 402
Cdd:cd15264  176 VWVLITKLRASNTLETIQYRKAVKATLVLLPLLGITYMLFfinpgddktSRLVFIYFNTFLQSF-----------QGLFV 244
                        250       260
                 ....*....|....*....|.
gi 672070171 403 AVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15264  245 AVFYCFLNGEVRSAIRKKFSR 265
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
173-423 9.41e-44

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: 155.12  E-value: 9.41e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAgsvlvIDWLLktRYSQKIGDD---LSVSVWlsdgavagCRVATVIMQYGIIANYCWLL 249
Cdd:cd15260   30 RSLRCTRITIHMNLFISFALNN-----LLWIV--WYKLVVDNPevlLENPIW--------CQALHVLLQYFMVCNYFWMF 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 250 VEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLF--ENVQCWTSNDNmgFWWILRIPVLLAILINFFI 327
Cdd:cd15260   95 CEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLpdDTERCWMEESS--YQWILIVPVVLSLLINLIF 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 328 FVRIIHLLVAKLRAHQMHYADYKFRLA-RSTLTLIPLLGVHEVVFAFVTDEHAqgTLRSTKLFFDLFFSSFQGLLVAVLY 406
Cdd:cd15260  173 LINIVRVLLTKLRATSPNPAPAGLRKAvRATLILIPLLGLQFLLIPFRPEPGA--PLETIYQYVSALLTSLQGLCVAVLF 250
                        250
                 ....*....|....*..
gi 672070171 407 CFLNKEVQAELLRRWRR 423
Cdd:cd15260  251 CFCNGEVIAAIKRKWRR 267
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
173-417 8.31e-43

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: 152.37  E-value: 8.31e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLVIDWLlktrysqkigddlsvsvwLSDGAVAGCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd13952   30 PKLRNLRGKILINLCLSLLLAQLLFLIGQLL------------------TSSDRPVLCKALAILLHYFLLASFFWMLVEA 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTF-SEKSFFSLYLCIGWGSPLLFVIPWVVVKCL-------FENVQCWTSNDNmGFWWILRIPVLLAILIN 324
Cdd:cd13952   92 FDLYRTFVKVFGsSERRRFLKYSLYGWGLPLLIVIITAIVDFSlygpspgYGGEYCWLSNGN-ALLWAFYGPVLLILLVN 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 325 FFIFVRIIHLLVAKLRAHQMHYADYKFR-LARSTLTLIPLLGVHEVVFAFVTDehaqGTLRSTKLFFDLFFSSFQGLLVA 403
Cdd:cd13952  171 LVFFILTVRILLRKLRETPKQSERKSDRkQLRAYLKLFPLMGLTWIFGILAPF----VGGSLVFWYLFDILNSLQGFFIF 246
                        250
                 ....*....|....
gi 672070171 404 VLYCFLNKEVQAEL 417
Cdd:cd13952  247 LIFCLKNKEVRRLL 260
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
175-423 5.49e-40

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: 145.20  E-value: 5.49e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 175 LHCTRNYIHGNLFASFVLKAgsvlvIDWLLktrysqkigdDLSVSVWlSDGAVAGCRVATVIMQYGIIANYCWLLVEGVY 254
Cdd:cd15263   32 LRCLRNTIHTNLMFTYILAD-----LTWIL----------TLTLQVS-IGEDQKSCIILVVLLHYFHLTNFFWMFVEGLY 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 255 LYsLLSITTFS-EKSFFSLYLCIGWGSPLLFVIPWVVVKClFENVQCWTSNDNMGFW------------WILRIPVLLAI 321
Cdd:cd15263   96 LY-MLVVETFSgENIKLRVYAFIGWGIPAVVIVIWAIVKA-LAPTAPNTALDPNGLLkhcpwmaehivdWIFQGPAILVL 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 322 LINFFIFVRIIHLLVAKLR-AHQMHYADYKfRLARSTLTLIPLLGV-HEVVFAFVTD-------EHAQGTLRSTklffdl 392
Cdd:cd15263  174 AVNLVFLVRIMWVLITKLRsANTVETQQYR-KAAKALLVLIPLLGItYILVIAGPTEgiaanifEYVRAVLLST------ 246
                        250       260       270
                 ....*....|....*....|....*....|.
gi 672070171 393 ffssfQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15263  247 -----QGFTVALFYCFLNTEVRNTLRHHFER 272
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
173-425 6.21e-38

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: 139.91  E-value: 6.21e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKagSVLVIDWLLKTRYSQKIGDDLSVSvwlsdgavagCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15274   30 RSLSCQRVTLHKNLFLSYILN--SIIIIIHLVAVVPNGELVARNPVS----------CKILHFIHQYMMGCNYFWMLCEG 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSNDNmGFWWILRIPVLLAILINFFIFVRII 332
Cdd:cd15274   98 IYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAITRAVYYNDNCWLSSET-HLLYIIHGPIMAALVVNFFFLLNIV 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 333 HLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQGTLRStklFFDLFFSSFQGLLVAVLYCFLNKE 412
Cdd:cd15274  177 RVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQFVLFPWRPSGKILGKIYD---YVMHSLIHFQGFFVATIFCFCNGE 253
                        250
                 ....*....|...
gi 672070171 413 VQAELLRRWRRWQ 425
Cdd:cd15274  254 VQATLKRQWNQYK 266
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
173-423 7.74e-35

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: 131.21  E-value: 7.74e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLVIDwllktrysqkigddLSVSVWLSDGAVAGCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15445   30 RSIRCLRNIIHWNLITAFILRNATWFVVQ--------------LTMSPEVHQSNVVWCRLVTAAYNYFHVTNFFWMFGEG 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSNdNMGFW--WILRIPVLLAILINFFIFVR 330
Cdd:cd15445   96 CYLHTAIVLTYSTDKLRKWMFICIGWCIPFPIIVAWAIGKLYYDNEKCWFGK-RAGVYtdYIYQGPMILVLLINFIFLFN 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 331 IIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFaFVTDEHAQGTlRSTKLFFDLFFSSFQGLLVAVLYCFLN 410
Cdd:cd15445  175 IVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLF-FVNPGEDEIS-RIVFIYFNSFLESFQGFFVSVFYCFLN 252
                        250
                 ....*....|...
gi 672070171 411 KEVQAELLRRWRR 423
Cdd:cd15445  253 SEVRSAVRKRWHR 265
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
173-423 3.73e-34

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: 129.79  E-value: 3.73e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKA--GSVLVIDwLLKTRYSQKIGDDLSVSVWLSDGAVAGCRVATVIMQYGIIANYCWLLV 250
Cdd:cd15261   30 RTLRNHRTRIHKNLFLAILLQViiRLVLYID-QAITRSRGSHTNAATTEGRTINSTPILCEGFYVLLEYAKTVMFMWMFI 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 251 EGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPW-VVVKCLFENVQCWTSNDNMGFWWILRIPVLLAILINFFIFV 329
Cdd:cd15261  109 EGLYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWaIVTLIKMKVNRCWFGYYLTPYYWILEGPRLAVILINLFFLL 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 330 RIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGV-----------HEVVFAFVTDEHAQGTLRStklffdlffssFQ 398
Cdd:cd15261  189 NIIRVLVSKLRESHSREIEQVRKAVKAAIVLLPLLGItnilqmippplTSVIVGFAVWSYSTHFLTS-----------FQ 257
                        250       260
                 ....*....|....*....|....*
gi 672070171 399 GLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15261  258 GFFVALIYCFLNGEVKNVLKKFWRR 282
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
173-423 2.56e-32

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: 124.30  E-value: 2.56e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAgsvlvIDWLLKTRYSQKIGDdlSVSVWlsdgavagCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15446   30 RSIRCLRNIIHWNLITTFILRN-----VMWFLLQMIDHNIHE--SNEVW--------CRCITTIYNYFVVTNFFWMFVEG 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSNDNMGFW-WILRIPVLLAILINFFIFVRI 331
Cdd:cd15446   95 CYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYENEQCWFGKEPGKYIdYIYQGPVILVLLINFVFLFNI 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 332 IHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFaFVT---DEHAQGTLrstkLFFDLFFSSFQGLLVAVLYCF 408
Cdd:cd15446  175 VRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLF-FVNpgeDDISQIVF----IYFNSFLQSFQGFFVSVFYCF 249
                        250
                 ....*....|....*
gi 672070171 409 LNKEVQAELLRRWRR 423
Cdd:cd15446  250 LNGEVRSAARKRWHR 264
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
173-423 1.01e-30

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: 119.86  E-value: 1.01e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLK------AGSVLVIDWLLKTrysqkiGDDLSVsvwlsDGAVAGCRVATVIMQYGIIANYC 246
Cdd:cd15262   30 KRLRITRVILHRNLLISIIIRnilviiSKVFVILDALTSS------GDDTVM-----NQNAVVCRLLSIFERAARNAVFA 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 247 WLLVEGVYLYSLLsITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQCWTSnDNMGFWWILRIPVLLAILINFF 326
Cdd:cd15262   99 CMFVEGFYLHRLI-VAVFAEKSSIRFLYVIGAVLPLFPVIIWAIIRALHNDHSCWVV-DIEGVQWVLDTPRLFILLVNTV 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 327 IFVRIIHLLVAKLRaHQMHYADYKFRLaRSTLTLIPLLGVHEVVFAF--VTDEHaqgTLRSTKLFFDLFFSSFQGLLVAV 404
Cdd:cd15262  177 LLVDIIRVLVTKLR-NTEENSQTKSTT-RATLFLVPLFGLHFVITAYrpSTDDC---DWEDIYYYANYLIEGLQGFLVAI 251
                        250
                 ....*....|....*....
gi 672070171 405 LYCFLNKEVQAELLRRWRR 423
Cdd:cd15262  252 LFCYINKEVHYLIKNTYRK 270
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
173-410 1.31e-30

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: 119.45  E-value: 1.31e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLVIDWLLKTRYSqkigddlsvsvwlSDGAVAGCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd14964   27 RKRPRSTRLLLASLAACDLLASLVVLVLFFLLGLTEA-------------SSRPQALCYLIYLLWYGANLASIWTTLVLT 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLY----SLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFEN------VQCWTSNDNMGFWWILRIPVLLAIL 322
Cdd:cd14964   94 YHRYfalcGPLKYTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRyntltgSCYLICTTIYLTWGFLLVSFLLPLV 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 323 INFFIFVRIIHLLVAKLRAH---QMHYADYKFRLARSTLTLIPLLGVHEVVFAFVTDEHAQ---GTLRSTKLFFDLFFSS 396
Cdd:cd14964  174 AFLVIFSRIVLRLRRRVRAIrsaASLNTDKNLKATKSLLILVITFLLCWLPFSIVFILHALvaaGQGLNLLSILANLLAV 253
                        250
                 ....*....|....
gi 672070171 397 FQGLLVAVLYCFLN 410
Cdd:cd14964  254 LASTLNPFIYCLGN 267
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
228-415 1.97e-22

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: 96.24  E-value: 1.97e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 228 AGCRVATVIMQYGIIANYCWLLVEGVYLYSLLsITTFSEKSFFSLYLCIGWGSPLLFVIpwVVVKCLFE----NVQCWTS 303
Cdd:cd15933   65 VACKVVAILLHFFFMAAFSWMLVEGLHLYLMI-VKVFNYKSKMRYYYFIGWGLPAIIVA--ISLAILFDdygsPNVCWLS 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 304 NDNmGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQ-MHYADYK--FRLARSTLTLIPLLGV-----------HEV 369
Cdd:cd15933  142 LDD-GLIWAFVGPVIFIITVNTVILILVVKITVSLSTNDAkKSQGTLAqiKSTAKASVVLLPILGLtwlfgvlvvnsQTI 220
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 672070171 370 VFAFVTdehaqGTLRSTklffdlffssfQGLLVAVLYCFLNKEVQA 415
Cdd:cd15933  221 VFQYIF-----VILNSL-----------QGLMIFLFHCVLNSEVRS 250
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
218-414 1.65e-21

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: 93.79  E-value: 1.65e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 218 VSVWLSDGAVaGCRVATVIMQYGIIANYCWLLVEGVYLYSLLsITTFSE--KSFFSLYLCIGWGSPLLfvipwVVVKCLF 295
Cdd:cd15040   57 FGINSTDNPV-LCTAVAALLHYFLLASFMWMLVEALLLYLRL-VKVFGTypRHFILKYALIGWGLPLI-----IVIITLA 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 296 ENVQ--------CWTSNDNmGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYKFRLARSTLTLIPLLGVH 367
Cdd:cd15040  130 VDPDsygnssgyCWLSNGN-GLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQLRAAVSLFFLLGLT 208
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 672070171 368 EV--VFAFVTDEHAQGTLRSTklffdlfFSSFQGLLVAVLYCFLNKEVQ 414
Cdd:cd15040  209 WIfgILAIFGARVVFQYLFAI-------FNSLQGFFIFIFHCLRNKEVR 250
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
61-128 8.30e-20

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: 83.19  E-value: 8.30e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672070171   61 ELVCNRTFDKYSCWPDTPPNTTANISCPWYLPWYHKVQHrlVFKRCGPDGQWVRGPRgqswRDASQCQ 128
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDPRGN--ASRNCTEDGTWSEHPP----SNYSNCT 62
HormR smart00008
Domain present in hormone receptors;
60-135 2.11e-19

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 82.18  E-value: 2.11e-19
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 672070171    60 SELVCNRTFDKYSCWPDTPPNTTANISCPWYLPWYHKVQHrlVFKRCGPDGQWvrgprGQSWRDASQCQMDDDEIE 135
Cdd:smart00008   1 TDLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTG--ASRNCTENGGW-----SPPFPNYSNCTSNDYEEL 69
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
179-415 2.79e-17

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: 81.51  E-value: 2.79e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 179 RNYIHGNLfaSFVLKAGSVLVIdwllktrysqkigddlsVSVWLSDGAVAgCRVATVIMQYGIIANYCWLLVEGVYLYSL 258
Cdd:cd15256   39 RYHIHANL--SFAVLVAQILLL-----------------ISFRFEPGTLP-CKIMAILLHFFFLSAFAWMLVEGLHLYSM 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 259 LSITTFSEKSFFSLYLCIGWGSPLLFVIPWVV--VKCLFENVQCWTSNDNmGFWWILRIPVLLAILINFFIFV---RIIH 333
Cdd:cd15256   99 VIKVFGSEESKHFYYYGIGWGSPLLICIISLTsaLDSYGESDNCWLSLEN-GAIWAFVAPALFVIVVNIGILIavtRVIS 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 334 LLVAKlrAHQMHYADYKFRL-ARSTLTLIPLLGVHEVVFAFVTDEHAqgtlrSTKLFFDLFFSSFQGLLVAVLYCFLNKE 412
Cdd:cd15256  178 RISAD--NYKVHGDANAFKLtAKAVAVLLPILGSSWVFGVLAVNTHA-----LVFQYMFAIFNSLQGFFIFLFHCLLNSE 250

                 ...
gi 672070171 413 VQA 415
Cdd:cd15256  251 VRA 253
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
230-423 7.71e-16

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: 77.29  E-value: 7.71e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 230 CRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKC-LFENVQ-CWTSNDNm 307
Cdd:cd15441   67 CKLIAILLHYFYLSAFSWLLVESLHLYRMLTEPRDINHGHMRFYYLLGYGIPAIIVGLSVGLRPdGYGNPDfCWLSVNE- 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 308 GFWWILRIPVLLAILINFFIFVRIIHLLVAKLRaHQMHYADYKFRLaRSTLTLIPLLGVhEVVFAFVTDEHAQGTLrstk 387
Cdd:cd15441  146 TLIWSFAGPIAFVIVITLIIFILALRASCTLKR-HVLEKASVRTDL-RSSFLLLPLLGA-TWVFGLLAVNEDSELL---- 218
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 672070171 388 LFFDLFFSSFQGLLVAVLYCFLNKEVQAELLRRWRR 423
Cdd:cd15441  219 HYLFAGLNFLQGLFIFLFYCIFNKKVRRELKNALLR 254
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
173-423 6.74e-14

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: 71.53  E-value: 6.74e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLkAGSVLVIdwllktrysqkigddlsvSVWLSDGAVaGCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15440   30 RNLQCDRNTIHKNLCLCLLI-AEIVFLL------------------GIDQTENRT-LCGVIAGLLHYFFLAAFSWMLLEG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVI--PWVVVKCLFENVQCWTSNDNmGFWWILRIPVLLAILINF-FIFV 329
Cdd:cd15440   90 FQLYVMLVEVFEPEKSRIKWYYLFGYGLPALIVAvsAGVDPTGYGTEDHCWLSTEN-GFIWSFVGPVIVVLLANLvFLGM 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 330 RIIHLLVAKLRAHQMHYAD--YKFRL-ARSTLTLIPLLGV-----------HEVVFAFV-TdehaqgTLRSTklffdlff 394
Cdd:cd15440  169 AIYVMCRHSSRSASKKDASklKNIRGwLKGSIVLVVLLGLtwtfgllfinqESIVMAYIfT------ILNSL-------- 234
                        250       260
                 ....*....|....*....|....*....
gi 672070171 395 ssfQGLLVAVLYCFLNKEVQAElLRRWRR 423
Cdd:cd15440  235 ---QGLFIFIFHCVLNEKVRKE-LRRWLR 259
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
173-424 3.49e-12

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: 66.71  E-value: 3.49e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAgsvlVIDWLLKTRYSQKIgddlsvsvwlsdgavaGCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15438   30 RSIRGTRNTIHLHLCLSLFLAH----LIFLLGINNTNNQV----------------ACAVVAGLLHYFFLAAFCWMSLEG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYsLLSITTFSEKSFFSLYLC-IGWGSPLLFVIPWVVV--KCLFENVQCWTSNDNmGFWWILRIPVLLAILINFFIFV 329
Cdd:cd15438   90 VELY-LMVVQVFNTQSLKKRYLLlIGYGVPLVIVAISAAVnsKGYGTQRHCWLSLER-GFLWSFLGPVCLIILVNAIIFV 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 330 RIIHLLVAKLRahQMHYADYKFRLARS-TLTLIPLLGVHEVVFAFVTDEHAQGTLRSTklFFDLFFSSFQGLLVAVLYCF 408
Cdd:cd15438  168 ITVWKLAEKFS--SINPDMEKLRKIRAlTITAIAQLCILGCTWIFGFFQFSDSTLVMS--YLFTILNSLQGLFIFLLHCL 243
                        250
                 ....*....|....*.
gi 672070171 409 LNKEVQAEllrrWRRW 424
Cdd:cd15438  244 LSKQVREE----YSRW 255
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
216-345 1.14e-10

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


Pssm-ID: 410632 [Multi-domain]  Cd Length: 270  Bit Score: 62.24  E-value: 1.14e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 216 LSVSVWLSDGAVAGCRVATVIMQYGIIANYCWLLVEGVYLY-----SLLSITTFSEKSFFSLYLCIGWGSPLLFVI---- 286
Cdd:cd15039   54 LLIGQLLSSGDSTLCVALGILLHFFFLAAFFWLNVMSFDIWrtfrgKRSSSSRSKERKRFLRYSLYAWGVPLLLVAvtii 133
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 672070171 287 -----PWVVVKCLFENVQCWTSNDNmGFWWILRIPVLLAILINFFIFVR-IIHLLVAKLRAHQMH 345
Cdd:cd15039  134 vdfspNTDSLRPGYGEGSCWISNPW-ALLLYFYGPVALLLLFNIILFILtAIRIRKVKKETAKVQ 197
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
229-424 2.20e-09

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


Pssm-ID: 320597 [Multi-domain]  Cd Length: 262  Bit Score: 58.30  E-value: 2.20e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 229 GCRVATVIMQYGIIANYCWLLVEGVYLY----SLLSITTFSEKSFFSLYLC-IGWGSPLLFVIPWVVV--KCLFENVQCW 301
Cdd:cd15931   66 ACTVMAGLLHYLFLASFVWMLLEALQLHllvrRLTKVQVIQRDGLPRPLLClIGYGVPFLIVGVSALVysDGYGEAKMCW 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 302 TSNDNmGFWWILRIPVLLAILINFFIFVRIIHLLVAKL---RAHQMHYADYKFRLARSTLTLIpLLGVHEVVFAFVTDEH 378
Cdd:cd15931  146 LSQER-GFNWSFLGPVIAIIGINWILFCATLWCLRQTLsnmNSDISQLKDTRLLTFKAVAQLF-ILGCTWVLGLFQTNPV 223
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 672070171 379 AqgtlrSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAEllrrWRRW 424
Cdd:cd15931  224 A-----LVFQYLFTILNSLQGAFLFLVHCLLNKEVREE----YIKW 260
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
173-423 3.76e-08

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: 54.50  E-value: 3.76e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLvidwllktrysqkIGDDLSVSVWLsdgavagCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15437   30 SEIQSTRTTIHKNLCCSLFLAELIFL-------------IGINMNANKLF-------CSIIAGLLHYFFLAAFAWMCIEG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQ--CWTSNDNmGFWWILRIPVLLAILINFFIFVR 330
Cdd:cd15437   90 IHLYLIVVGVIYNKGFLHKNFYIFGYGSPAVVVGISAALGYKYYGTTkvCWLSTEN-NFIWSFIGPACLIILVNLLAFGV 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 331 IIHLL---VAKLRAHQMHYADYKfRLARSTLTLIPLLGVhevVFAFVTDEHAQGTLRSTklFFDLFFSSFQGLLVAVLYC 407
Cdd:cd15437  169 IIYKVfrhTAMLKPEVSCYENIR-SCARGALALLFLLGA---TWIFGVLHVVYGSVVTA--YLFTISNAFQGMFIFIFLC 242
                        250
                 ....*....|....*.
gi 672070171 408 FLNKEVQAELLRRWRR 423
Cdd:cd15437  243 VLSRKIQEEYYRLFKN 258
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
216-419 3.97e-08

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: 54.47  E-value: 3.97e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 216 LSVSVWLSDGAVAgCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLlfVIPWVVVKCLF 295
Cdd:cd15255   54 LMFSEWAKGNQVA-CWAVTALLHLFFLAAFSWMLVEGLLLWSKVVAVNMSEDRRMKFYYVTGWGLPV--VIVAVTLATSF 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 296 ENV----QCWTsNDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAH----------QMHYADYKFRLARSTLTLI 361
Cdd:cd15255  131 NKYvadqHCWL-NVQTDIIWAFVGPVLFVLTVNTFVLFRVVMVTVSSARRRakmltpssdlEKQIGIQIWATAKPVLVLL 209
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 672070171 362 PLLGVHEVVFAFVtdehaqgTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAELLR 419
Cdd:cd15255  210 PVLGLTWLCGVLV-------HLSDVWAYVFITLNSFQGLYIFLVYAIYNSEVRNAIQR 260
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
173-422 2.90e-07

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: 51.74  E-value: 2.90e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLV-IDwllktRYSQKIGddlsvsvwlsdgavagCRVATVIMQYGIIANYCWLLVE 251
Cdd:cd15252   30 RGLQSDRTTIHKNLCISLFLAELVFLIgIN-----TTTNKIF----------------CSVIAGLLHYFFLAAFAWMFIE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 252 GVYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVVKCLFENVQ--CWTSNDNMgFWWILRIPVLLAILINFFIFV 329
Cdd:cd15252   89 GIQLYLMLVEVFENEGSRHKNFYIFGYGSPAVIVGVSAALGYRYYGTTkvCWLSTENY-FIWSFIGPATLIILLNLIFLG 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 330 RIIHLL---VAKLRAHQMHYADYKfRLARSTLTLIPLLGVhEVVFAFVTDEHAQGTLrstkLFFDLFFSSFQGLLVAVLY 406
Cdd:cd15252  168 VAIYKMfrhTAGLKPEVSCLENIR-SWARGAIALLFLLGL-TWIFGVLHINHASVVM----AYLFTVSNSLQGMFIFLFH 241
                        250
                 ....*....|....*.
gi 672070171 407 CFLNKEVQAELLRRWR 422
Cdd:cd15252  242 CVLSRKVRKEYYKLFR 257
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
229-421 6.57e-07

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


Pssm-ID: 320555 [Multi-domain]  Cd Length: 263  Bit Score: 50.80  E-value: 6.57e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 229 GCRVATVIMQYGIIANYCWLLVEGVYLY----SLLSITTFSEKSFFSLYLC-IGWGSPLLFVipwVVVKCLFEN-----V 298
Cdd:cd15439   66 LCSIIAGFLHYLFLACFAWMFLEAVHLFltvrNLKVVNYFSSHRFKKRFMYpVGYGLPAVIV---AISAAVNPQgygtpK 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 299 QCWTSNDNmGFWWILRIPVLLAILINFFIFVRIIHLL----------VAKLRAHQMhyadykfrLARSTLTLIPLLGVHE 368
Cdd:cd15439  143 HCWLSMEK-GFIWSFLGPVCVIIVINLVLFCLTLWILreklsslnaeVSTLKNTRL--------LTFKAIAQLFILGCTW 213
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 672070171 369 VVFAFVTdehaqGTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQaELLRRW 421
Cdd:cd15439  214 ILGLFQV-----GPVATVMAYLFTITNSLQGVFIFLVHCLLNRQVR-EEYRRW 260
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
173-416 1.62e-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: 1.62e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLkaGSVLVIDWLLKTRYSqkigddlsvsvwlsdgavAGCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd16007   30 RGLQTDRNTIHKNLCINLFL--AELLFLIGIDKTQYQ------------------IACPIFAGLLHFFFLAAFSWLCLEG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFV--IPWVVVKCLFENVQCWTSNDNMgFWWILRIPVLLAILINFFIFVR 330
Cdd:cd16007   90 VQLYLMLVEVFESEYSRKKYYYLCGYCFPALVVgiSAAIDYRSYGTEKACWLRVDNY-FIWSFIGPVSFVIVVNLVFLMV 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 331 IIHLLV---AKLRAHQMHYADYKfRLARSTLTLIPLLGVHEVV-FAFVTDEHAQGTLRSTklffdlFFSSFQGLLVAVLY 406
Cdd:cd16007  169 TLHKMIrssSVLKPDSSRLDNIK-SWALGAITLLFLLGLTWAFgLLFINKESVVMAYLFT------TFNAFQGMFIFIFH 241
                        250
                 ....*....|
gi 672070171 407 CFLNKEVQAE 416
Cdd:cd16007  242 CALQKKVHKE 251
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
173-422 8.32e-06

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: 47.48  E-value: 8.32e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLkaGSVLVIDWLLKTRYSqkigddlsvsvwlsdgavAGCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd15436   30 RGLQTDRNTIHKNLCINLFI--AELLFLIGINRTQYT------------------IACPIFAGLLHFFFLAAFCWLCLEG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVV--KCLFENVQCWTSNDNMgFWWILRIPVLLAILINFFIFVR 330
Cdd:cd15436   90 VQLYLLLVEVFESEYSRRKYFYLCGYSFPALVVAVSAAIdyRSYGTEKACWLRVDNY-FIWSFIGPVTFVITLNLVFLVI 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 331 IIHLLV--AKLRAHQMHYADYKFRLARSTLTLIPLLGVhevVFAFVTDEHAQGTLrsTKLFFDLFFSSFQGLLVAVLYCF 408
Cdd:cd15436  169 TLHKMVshSDLLKPDSSRLDNIKSWALGAIALLFLLGL---TWSFGLMFINEESV--VMAYLFTIFNAFQGVFIFIFHCA 243
                        250
                 ....*....|....
gi 672070171 409 LNKEVQAELLRRWR 422
Cdd:cd15436  244 LQKKVRKEYSKCLR 257
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
230-415 2.26e-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: 45.99  E-value: 2.26e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 230 CRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLlfVIPWVVVKCLFENVQ----CWTSND 305
Cdd:cd15993   67 CTVVAILLHYFFLSTFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPA--IITGLAVGLDPEGYGnpdfCWISIH 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 306 NMgFWWILRIPVLLAILINFFIFVRIIHLL-------VAKLRAHQMHYADYKFRLARSTLTLIPLLGVHEVVFAFvtdeh 378
Cdd:cd15993  145 DK-LVWSFAGPIVVVIVMNGVMFLLVARMScspgqkeTKKTSVLMTLRSSFLLLLLISATWLFGLLAVNNSVLAF----- 218
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 672070171 379 aqgtlrstkLFFDLFFSSFQGLLVAVLYCFLNKEVQA 415
Cdd:cd15993  219 ---------HYLHAILCCLQGLAVLLLFCVLNEEVQE 246
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
221-422 7.37e-05

Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR112 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR64, GPR97, GPR114, and GPR126. GPR112 is specifically expressed in normal enterochromatin cells and gastrointestinal neuroendocrine carcinoma cells, but its biological function is unknown. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320663  Cd Length: 269  Bit Score: 44.65  E-value: 7.37e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 221 WLSD-GAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCI-GWGSPLLFVIPWVVV-KCLFEN 297
Cdd:cd15997   60 WLSSfNNYGLCITVAAFLHYFLLASFTWMGLEAVHMYFALVKVFNIYIPNYILKFCIaGWGIPAVVVALVLAInKDFYGN 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 298 VQ-----------CWTSNDnmgfwWILRIPV----LLAILINFFIFVRI-IHLLVAKLRAHQMHYADYKFRLARSTLTLI 361
Cdd:cd15997  140 ELssdslhpstpfCWIQDD-----VVFYISVvayfCLIFLCNISMFITVlIQIRSMKAKKPSRNWKQGFLHDLKSVASLT 214
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 672070171 362 PLLGVhEVVFAFVtdehAQGTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQaellRRWR 422
Cdd:cd15997  215 FLLGL-TWGFAFF----AWGPVRIFFLYLFSICNTLQGFFIFVFHCLMKENVR----KQWR 266
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
218-416 1.23e-04

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: 43.94  E-value: 1.23e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 218 VSVWL-SDGAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLS--ITTFSEKSFFSLYLcIGWGSPLLFVIPWVVVK-- 292
Cdd:cd15258   57 LSSWIaSFGSDGLCIAVAVALHYFLLACLTWMGLEAFHLYLLLVkvFNTYIRRYILKLCL-VGWGLPALLVTLVLSVRsd 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 293 -------CLFENVQ----CWTSNDnmgfwWILRIPVLLAILINFFIFVRIIHLLVAKL----RAHQMHYADYKFRLARST 357
Cdd:cd15258  136 nygpitiPNGEGFQndsfCWIRDP-----VVFYITVVGYFGLTFLFNMVMLATVLVQIcrlrEKAQATPRKRALHDLLTL 210
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 672070171 358 LTLIPLLGVhEVVFAFVtdehAQGTLRSTKLFFDLFFSSFQGLLVAVLYCFLNKEVQAE 416
Cdd:cd15258  211 LGLTFLLGL-TWGLAFF----AWGPFNLPFLYLFAIFNSLQGFFIFIWYCSMKENVRKQ 264
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
230-417 1.24e-04

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: 43.68  E-value: 1.24e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 230 CRVATVIMQYGIIANYCWLLVEGVYLYSLLSITTFSEKSFFSLYLCIGWGSPLlfVIPWVVVKCLFENVQ----CWTSND 305
Cdd:cd15991   67 CTVVAILLHYFYMSTFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPA--IITGLAVGLDPQGYGnpdfCWLSVQ 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 306 NMGFWWILRiPVLLAILINFFIFVriihlLVAKLRAHQMHYADYK------FRLARSTLTLIP------LLGVHEVVFAF 373
Cdd:cd15991  145 DTLIWSFAG-PIGIVVIINTVIFV-----LAAKASCGRRQRYFEKsgvismLRTAFLLLLLISatwllgLMAVNSDTLSF 218
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 672070171 374 vtdeHAQGTLRSTklffdlffssFQGLLVAVLYCFLNKEVQAEL 417
Cdd:cd15991  219 ----HYLFAIFSC----------LQGIFIFFFHCIFNKEVRKHL 248
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
230-414 3.45e-04

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


Pssm-ID: 320379  Cd Length: 253  Bit Score: 42.24  E-value: 3.45e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 230 CRVATVIMQYGIIANYCWLLVEGVYLYsLLSITTFSEKSFFSLYLCIGWGSPLLFV---IPWVVVKCLFENVQCWTSNDN 306
Cdd:cd15251   68 CTMTAAFLHFFFLSSFCWVLTEAWQSY-MAVTGRMRTRLIRKRFLCLGWGLPALVVavsVGFTRTKGYGTSSYCWLSLEG 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 307 mGFWWILRIPVLLAILINFFIFVRIIHLLVAKlrahqMHYADYKFRLARSTLTLIPLLGV--HEVVFAfVTDEHAqgtlr 384
Cdd:cd15251  147 -GLLYAFVGPAAAVVLVNMVIGILVFNKLVSR-----DGISDNAMASLWSSCVVLPLLALtwMSAVLA-MTDRRS----- 214
                        170       180       190
                 ....*....|....*....|....*....|
gi 672070171 385 STKLFFDLFFSSFQGLLVAVLYCFLNKEVQ 414
Cdd:cd15251  215 VLFQILFAVFDSLQGFVIVMVHCILRREVQ 244
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
181-312 2.59e-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: 39.74  E-value: 2.59e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 181 YIHGNLFASFVLKAGSVLvidwllktrysqkigddLSVSVWLSDgAVAGCRVATVIMQYGIIANYCWLLVEGVYLYSLLS 260
Cdd:cd15443   39 RIHMNLLGSLFLLNGSFL-----------------LSPPLATSQ-STWLCRAAAALLHYSLLCCLTWMAIEGFHLYLLLV 100
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 672070171 261 ITTFSEKSFFSLYLC-IGWGSPLLFVIPWVVVKCL---FENVQCWTSNDNMGFWWI 312
Cdd:cd15443  101 KVYNIYIRRYVLKLCvLGWGLPALIVLLVLIFKREaygPHTIPTGTGYQNASMCWI 156
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
229-365 3.26e-03

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


Pssm-ID: 320598 [Multi-domain]  Cd Length: 268  Bit Score: 39.22  E-value: 3.26e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 229 GCRVATVIMQYGIIANYCWLLVEGVYL-YSLLSI-TTFSEKSFFSLYLCIGWGSPLLFVIPWVVV----KCLFENVQCWT 302
Cdd:cd15932   75 ACTAATFFIHFFYLALFFWMLTLGLLLfYRLVLVfHDMSKSTMMAIAFSLGYGCPLIIAIITVAAtapqGGYTRKGVCWL 154
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 672070171 303 SNDNMGFWWILRIPVLLAILINFFIFVRIIHLLVAKLRAHQMHYADYK--FRLARSTLTLIPLLG 365
Cdd:cd15932  155 NWDKTKALLAFVIPALAIVVVNFIILIVVIFKLLRPSVGERPSKDEKNalVQIGKSVAILTPLLG 219
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
230-338 3.65e-03

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


Pssm-ID: 320655 [Multi-domain]  Cd Length: 293  Bit Score: 39.28  E-value: 3.65e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 230 CRVATVIMQYGIIANYCWLLVEGVYLYSLLSiTTFSEKSFFSLYLCIGWGSPLLFV---IPWVVVKCLFENVQCWTSNDN 306
Cdd:cd15989   70 CTMTTAFLHFFFLASFCWVLTEAWQSYMAVT-GKIRTRLIRKRFLCLGWGLPALVVaisMGFTKAKGYGTPHYCWLSLEG 148
                         90       100       110
                 ....*....|....*....|....*....|..
gi 672070171 307 mGFWWILRIPVLLAILINFFIFVRIIHLLVAK 338
Cdd:cd15989  149 -GLLYAFVGPAAAVVLVNMVIGILVFNKLVSR 179
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
230-338 6.87e-03

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


Pssm-ID: 320654 [Multi-domain]  Cd Length: 291  Bit Score: 38.40  E-value: 6.87e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 230 CRVATVIMQYGIIANYCWLLVEGVYLYsLLSITTFSEKSFFSLYLCIGWGSPLLFV---IPWVVVKCLFENVQCWTSNDN 306
Cdd:cd15988   68 CTMTAAFLHFFFLSSFCWVLTEAWQSY-LAVIGRMRTRLVRKRFLCLGWGLPALVVavsVGFTRTKGYGTASYCWLSLEG 146
                         90       100       110
                 ....*....|....*....|....*....|..
gi 672070171 307 mGFWWILRIPVLLAILINFFIFVRIIHLLVAK 338
Cdd:cd15988  147 -GLLYAFVGPAAVIVLVNMLIGIIVFNKLMSR 177
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
173-324 7.85e-03

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


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 38.00  E-value: 7.85e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672070171 173 RKLHCTRNYIHGNLFASFVLKAGSVLVidwllktrysqkigddlsvSVWLSDGAVAgCRVATVIMQYGIIANYCWLLVEG 252
Cdd:cd16005   30 RGLQSDRNTIHKNLCISLFVAELLFLI-------------------GINRTDQPIA-CAVFAALLHFFFLAAFTWMFLEG 89
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 672070171 253 VYLYSLLSITTFSEKSFFSLYLCIGWGSPLLFVIPWVVV--KCLFENVQCWTSNDNMgFWWILRIPVLLAILIN 324
Cdd:cd16005   90 VQLYIMLVEVFESEHSRRKYFYLVGYGMPALIVAVSAAVdyRSYGTDKVCWLRLDTY-FIWSFIGPATLIIMLN 162
 
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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