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Conserved domains on  [gi|296080761|ref|NP_001171673|]
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parathyroid hormone/parathyroid hormone-related peptide receptor precursor [Homo sapiens]

Protein Classification

hormone receptor( domain architecture ID 12039890)

hormone receptor is a class B G-protein coupled receptor (GPCR) for hormones and/or hormone-related peptides; contains a large N-terminal extracellular domain that plays a critical role in peptide hormone recognition; GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins by binding to an extracellular agonist, which induces conformational changes that lead to the activation of heterotrimeric G proteins, which then bind to and activate numerous downstream effector proteins

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
184-476 0e+00

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


The actual alignment was detected with superfamily member cd15984:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 290  Bit Score: 571.89  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEELRA 263
Cdd:cd15984    1 FDRLYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGSALEEMERITEEDLKS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 IAQAPPPPATAAAgyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15984   81 ITEAPPADKAQFV---GCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVR 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15984  158 ATLADTGCWDLSAGNLKWIIQVPILAAIVVNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 237
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296080761 424 FMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15984  238 FMAMPYTEVSGILWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 290
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
105-173 2.70e-24

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: 95.90  E-value: 2.70e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 296080761  105 GRPCLPEWDHILCWPLGAPGEVVAVPCPDYIYDFNHKGHAYRRCDRNGSWELVPGHnrtwaNYSECVKF 173
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDPRGNASRNCTEDGTWSEHPPS-----NYSNCTSN 64
 
Name Accession Description Interval E-value
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
184-476 0e+00

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: 571.89  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEELRA 263
Cdd:cd15984    1 FDRLYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGSALEEMERITEEDLKS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 IAQAPPPPATAAAgyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15984   81 ITEAPPADKAQFV---GCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVR 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15984  158 ATLADTGCWDLSAGNLKWIIQVPILAAIVVNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 237
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296080761 424 FMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15984  238 FMAMPYTEVSGILWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 290
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
184-455 7.19e-110

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: 329.24  E-value: 7.19e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761  184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLteeelra 263
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLDHCSWV------- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761  264 iaqappppataaagyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSV- 342
Cdd:pfam00002  74 ----------------GCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVd 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761  343 -RATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRqQYRKLLKSTLVLMPLFGVHY 421
Cdd:pfam00002 138 pKGYGEDDGCWLSNENGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLK-QYRRLAKSTLLLLPLLGITW 216
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 296080761  422 I--VFMATPYTevsgTLWQVQMHYEMLFNSFQGFFV 455
Cdd:pfam00002 217 VfgLFAFNPEN----TLRVVFLYLFLILNSFQGFFV 248
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
105-173 2.70e-24

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: 95.90  E-value: 2.70e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 296080761  105 GRPCLPEWDHILCWPLGAPGEVVAVPCPDYIYDFNHKGHAYRRCDRNGSWELVPGHnrtwaNYSECVKF 173
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDPRGNASRNCTEDGTWSEHPPS-----NYSNCTSN 64
HormR smart00008
Domain present in hormone receptors;
105-179 6.18e-22

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 89.50  E-value: 6.18e-22
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296080761   105 GRPCLPEWDHILCWPLGAPGEVVAVPCPDYIYDFNHKGHAYRRCDRNGSWElvpghnRTWANYSECVKFLTNETR 179
Cdd:smart00008   2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTGASRNCTENGGWS------PPFPNYSNCTSNDYEELK 70
 
Name Accession Description Interval E-value
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
184-476 0e+00

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: 571.89  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEELRA 263
Cdd:cd15984    1 FDRLYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGSALEEMERITEEDLKS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 IAQAPPPPATAAAgyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15984   81 ITEAPPADKAQFV---GCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVR 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15984  158 ATLADTGCWDLSAGNLKWIIQVPILAAIVVNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 237
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296080761 424 FMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15984  238 FMAMPYTEVSGILWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 290
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
184-476 0e+00

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: 563.54  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEELra 263
Cdd:cd15265    1 FERLYLIYTVGYSISLVSLTVAVFILGYFRRLHCTRNYIHMHLFVSFMLRAVSIFVKDAVLYSGSGLDELERPSMEDL-- 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 iAQAPPPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15265   79 -KSIVEAPPVDKSQYVGCKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVFVIPWASVR 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15265  158 ATLADTRCWDLSAGNYKWIYQVPILAAIVVNFILFLNIVRVLATKLRETNAGRCDTRQQYRKLAKSTLVLIPLFGVHYIV 237
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296080761 424 FMATPYTEVsGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15265  238 FMGMPYTEV-GLLWQIRMHYELFFNSFQGFFVAIIYCFCNGEVQAEIKKRWER 289
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
184-476 3.61e-164

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: 469.40  E-value: 3.61e-164
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEelra 263
Cdd:cd15983    1 FERLHLMYTIGYSISLAALLVAVCILCYFKRLHCTRNYIHIHLFASFICRAGSIFVKDAVLYSGTNEGEALDEKIE---- 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 iaqaPPPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15983   77 ----FGLSPGTRLQWVGCKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVR 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15983  153 VSLADTQCWDLSAGNLKWIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKLDPRQQYRKLLKSTLVLMPLFGVHYVL 232
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296080761 424 FMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15983  233 FMAMPYTDVTGLLWQIQMHYEMLFNSSQGFFVAFIYCFCNGEVQAEIKKAWLR 285
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
184-476 9.48e-148

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: 427.81  E-value: 9.48e-148
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEELRA 263
Cdd:cd15982    1 FERLYIMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAASIFVKDKVVHTHIGVKELDAVLMNDFQN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 IAQAPPPPATAAAgyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15982   81 AVDAPPVDKSQYV---GCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAAWAVVR 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15982  158 ATLADARCWELSAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWETNAVGYDTRKQYRKLAKSTLVLVLVFGVHYIV 237
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296080761 424 FMATPYTeVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15982  238 FVCLPHT-FTGLGWEIRMHCELFFNSFQGFFVSIIYCYCNGEVQTEIKKTWTR 289
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
189-476 2.23e-120

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: 356.92  E-value: 2.23e-120
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 189 MIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEElraiaqap 268
Cdd:cd15041    6 YIYLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFLSFILRAVFWIIWDLLVVYDRLTSSGVETVLMQ-------- 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 269 pppataaaGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLAN 348
Cdd:cd15041   78 --------NPVGCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSSLKLYYAIGWGLPLVIVVIWAIVRALLSN 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 349 TGCW-DLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRcdtRQQYRKLLKSTLVLMPLFGVHYIVFMAT 427
Cdd:cd15041  150 ESCWiSYNNGHYEWILYGPNLLALLVNLFFLINILRILLTKLRSHPNAE---PSNYRKAVKATLILIPLFGIQYLLTIYR 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 296080761 428 PYTEVsgTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15041  227 PPDGS--EGELVYEYFNAILNSSQGFFVAVIYCFLNGEVQSELKRKWSR 273
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
184-455 7.19e-110

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: 329.24  E-value: 7.19e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761  184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLteeelra 263
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLDHCSWV------- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761  264 iaqappppataaagyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSV- 342
Cdd:pfam00002  74 ----------------GCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVd 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761  343 -RATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRqQYRKLLKSTLVLMPLFGVHY 421
Cdd:pfam00002 138 pKGYGEDDGCWLSNENGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLK-QYRRLAKSTLLLLPLLGITW 216
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 296080761  422 I--VFMATPYTevsgTLWQVQMHYEMLFNSFQGFFV 455
Cdd:pfam00002 217 VfgLFAFNPEN----TLRVVFLYLFLILNSFQGFFV 248
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
185-476 1.01e-105

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: 320.10  E-value: 1.01e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 185 DRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLdeaerlteEELRAI 264
Cdd:cd15272    2 PSIRLMYNIGYGLSLVSLLIAVIIMLYFKKLHCPRNTIHINLFVSFILRAVLSFIKENLLVQGVGF--------PGDVYY 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 265 AQAPPPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRA 344
Cdd:cd15272   74 DSNGVIEFKDEGSHWECKLFFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLLFVLPWVFVRA 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 345 TLANTGCWDLSSgNKK--WIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDtRQQYRKLLKSTLVLMPLFGVHYI 422
Cdd:cd15272  154 TLEDTLCWNTNT-NKGyfWIIRGPIVISIAINFLFFINIVRVLFTKLKASNTQESR-PFRYRKLAKSTLVLIPLFGVHYM 231
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 296080761 423 VFMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15272  232 VFVVLPDSMSSDEAELVWLYFEMFFNSFQGFIVALLFCFLNGEVQSEIKKKWQR 285
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
184-476 2.81e-105

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: 318.22  E-value: 2.81e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTeeelra 263
Cdd:cd15275    1 FMYLKTMYTVGYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFIKDAVLFSSEDDNHCDIYT------ 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 iaqappppataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15275   75 ---------------VGCKVAMVFSNYCIMANYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFIISWAIAR 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDL-SSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTrQQYRKLLKSTLVLMPLFGVHYI 422
Cdd:cd15275  140 YLHENEGCWDTrRNAWIWWIIRGPVILSIFVNFILFLNILRILMRKLRAPDMRGNEF-SQYKRLAKSTLLLIPLFGLHYI 218
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 296080761 423 VFMATPYtEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15275  219 LFAFFPE-DVSSGTMEIWLFFELALGSFQGFVVAVLYCFLNGEVQLEIQRKWRR 271
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
184-476 8.15e-105

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: 317.07  E-value: 8.15e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTeeelra 263
Cdd:cd15930    1 YLTVKIIYTVGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKDAVLFSSEDVDHCFVST------ 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 iaqappppataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15930   75 ---------------VGCKASMVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVWIVAR 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKK-WIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTrQQYRKLLKSTLVLMPLFGVHYI 422
Cdd:cd15930  140 LYFEDTGCWDINDESPYwWIIKGPILISILVNFVLFINIIRILLQKLRSPDIGGNES-SQYKRLARSTLLLIPLFGIHYI 218
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 296080761 423 VFMATPytevSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15930  219 VFAFFP----ENISLGIRLYFELCLGSFQGFVVAVLYCFLNGEVQAEIKRKWRS 268
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
184-474 1.73e-103

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: 313.59  E-value: 1.73e-103
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTeeelra 263
Cdd:cd15271    1 FSTVKLLYTVGYGTSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALAVFIKDAVLFADESVDHCTMST------ 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 iaqappppataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15271   75 ---------------VACKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVWVLTR 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTrQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15271  140 LQYDNRGCWDDLESRIWWIIKTPILLSVFVNFLIFINVIRILVQKLKSPDVGGNDT-SHYMRLAKSTLLLIPLFGVHYVV 218
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 296080761 424 FMATPytEVSGTlwQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSW 474
Cdd:cd15271  219 FAFFP--EHVGV--EARLYFELVLGSFQGFIVALLYCFLNGEVQAEIKKRL 265
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
191-476 7.62e-99

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: 301.77  E-value: 7.62e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 191 YTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAerlteeelraiaqappp 270
Cdd:cd15269    8 YTIGHSLSLISLTAAMIILCLFRKLHCTRNYIHMHLFMSFILRAIAVFIKDAVLFESGEEDHC----------------- 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 271 pataAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANTG 350
Cdd:cd15269   71 ----SVASVGCKAAMVFFQYCIMANFFWLLVEGLYLHTLLAVSFFSERKYFWWYILIGWGAPSVFITAWSVARIYFEDVG 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 351 CWD-LSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTrQQYRKLLKSTLVLMPLFGVHYIVFMATPy 429
Cdd:cd15269  147 CWDtIIESLLWWIIKTPILVSILVNFILFICIIRILVQKLHSPDIGRNES-SQYSRLAKSTLLLIPLFGIHYIMFAFFP- 224
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 296080761 430 tevSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15269  225 ---DNFKAEVKLVFELILGSFQGFVVAVLYCFLNGEVQAELKRKWRR 268
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
186-476 1.95e-94

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: 290.87  E-value: 1.95e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 186 RLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVL---YSGATLDEAerlteeelr 262
Cdd:cd15929    3 SLQVMYTVGYSLSLAALVLALAILLGLRKLHCTRNYIHANLFASFILRALSVLVKDALLprrYSQKGDQDL--------- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 263 aiaqapPPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSV 342
Cdd:cd15929   74 ------WSTLLSNQASLGCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLLLGWGAPVLFVVPWGIV 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 343 RATLANTGCWDlSSGNKK--WIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRqqYRkLLKSTLVLMPLFGVH 420
Cdd:cd15929  148 KYLYENTGCWT-RNDNMAywWIIRLPILLAILINFFIFVRILKILVSKLRANQMCKTDYK--FR-LAKSTLTLIPLLGVH 223
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 296080761 421 YIVFMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15929  224 EVVFAFVTDEQARGTLRFIKLFFELFLSSFQGLLVAVLYCFANKEVQSELRKKWHR 279
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
184-476 2.47e-91

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: 282.46  E-value: 2.47e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEelra 263
Cdd:cd15270    1 FSTVKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFIKDAALFQEDDTDHCSMSTVL---- 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 iaqappppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15270   77 -----------------CKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCK 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKK-WIIQVPILASIVLNFILFINIVRVLATKLrETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYI 422
Cdd:cd15270  140 LYFEDTECWDINNDSPYwWIIKGPIVISVGVNFLLFLNIIRILLKKL-DPRQINFNNSAQYRRLSKSTLLLIPLFGTHYI 218
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 296080761 423 VFMATP-YTEVSGTLWqvqmhYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15270  219 IFNFLPdYAGLGIRLY-----LELCLGSFQGFIVAVLYCFLNQEVQTEISRKWYG 268
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
190-474 1.78e-89

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: 277.46  E-value: 1.78e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 190 IYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEeelraiaqapp 269
Cdd:cd15986    7 IYTLGHSVSLIALTTGSTILCLFRKLHCTRNYIHLNLFFSFILRAISVLVKDDILYSSSNTEHCTVPPS----------- 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 270 ppataaagYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIfMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANT 349
Cdd:cd15986   76 --------LIGCKVSLVILQYCIMANFYWLLVEGLYLHTLL-VVIFSENRHFIVYLLIGWGIPTVFIIAWIVARIYLEDT 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 350 GCWDLSS-GNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDtRQQYRKLLKSTLVLMPLFGVHYIVFMATP 428
Cdd:cd15986  147 GCWDTNDhSVPWWVIRIPIIISIILNFILFISIIRILLQKLRSPDVGGND-QSQYKRLAKSTLLLIPLFGVHYIVFVYFP 225
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 296080761 429 YTEVSgtlwQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSW 474
Cdd:cd15986  226 DSSSS----NYQIFFELCLGSFQGLVVAILYCFLNSEVQGELKRKW 267
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
190-476 8.19e-89

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: 276.56  E-value: 8.19e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 190 IYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLdeaerltEEELRAIAQAPP 269
Cdd:cd15273    7 ISQIGYIVSLITLIIAFAIFLSFKKLHCARNKLHMHLFASFILRAFMTLLKDSLFIDGLGL-------LADIVERNGGGN 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 270 PPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANT 349
Cdd:cd15273   80 EVIANIGSNWVCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVPWIVARILFENS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 350 GCWDL-SSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRcdtRQQYRKLLKSTLVLMPLFGVHYIVFMATP 428
Cdd:cd15273  160 LCWTTnSNLLNFLIIRIPIMISVLINFILFLNIVRVLLVKLRSSVNED---SRRYKKWAKSTLVLVPLFGVHYTIFLILS 236
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 296080761 429 YTEVSGTLWQVQ-MHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15273  237 YLDDTNEAVELIwLFCDQLFASFQGFFVALLYCFLNGEVRAEIQRKWRR 285
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
187-476 4.28e-87

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: 271.62  E-value: 4.28e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSgatlDEAERLTEEelraiaq 266
Cdd:cd15266    4 LQLIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDIVLYS----TYSKRPDDE------- 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 APPPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATL 346
Cdd:cd15266   73 TGWISYLSEESSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVVPWGVAKILL 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 347 ANTGCWdLSSGNKK--WIIQVPILASIVLNFILFINIVRVLATKLRETNAgrCDTRQQYRkLLKSTLVLMPLFGVHYIVF 424
Cdd:cd15266  153 ENTGCW-GRNENMGiwWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQM--RFTDYKYR-LARSTLVLIPLLGIHEVVF 228
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 296080761 425 MATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15266  229 SFITDEQVEGFSRHIRLFIQLTLSSFQGFLVAVLYCFANGEVKAELKKRWQL 280
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
190-475 1.68e-80

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: 254.51  E-value: 1.68e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 190 IYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEelraiaqapp 269
Cdd:cd15987    7 LYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQDSDHCFVSTVE---------- 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 270 ppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANT 349
Cdd:cd15987   77 -----------CKAVMVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLRLHFDDT 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 350 GCWDLSSGNKK-WIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTrQQYRKLLKSTLVLMPLFGVHYIVFMATP 428
Cdd:cd15987  146 GCWDMNDNTALwWVIKGPVVGSIMINFVLFIGIIIILVQKLQSPDIGGNES-SIYLRLARSTLLLIPLFGIHYTVFAFSP 224
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 296080761 429 yTEVSGtlwQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWS 475
Cdd:cd15987  225 -ENVSK---RERLVFELGLGSFQGFVVAVLYCFLNGEVQSEIKRKWR 267
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
189-474 6.09e-75

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: 240.22  E-value: 6.09e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 189 MIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLysgatldeAERLTEEELRaiaQAP 268
Cdd:cd15985    6 MLYTVGYTLSLLTLVSALLILTSIRKLHCTRNYIHANLFASFILRAVSVIVKDTLL--------ERRWGREIMR---VAD 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 269 PPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLAN 348
Cdd:cd15985   75 WGELLSHKAAIGCRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVLFVVPWMLAKYLKEN 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 349 TGCWDLSSGNKK-WIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRqqyRKLLKSTLVLMPLFGVHYIVFMAT 427
Cdd:cd15985  155 KECWALNENMAYwWIIRIPILLASLINLLIFMRILKVILSKLRANQKGYADYK---LRLAKATLTLIPLFGIHEVVFIFA 231
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 296080761 428 PYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSW 474
Cdd:cd15985  232 TDEQTTGILRYIKVFFTLFLNSFQGFLVAVLYCFANKEVKSELLKKW 278
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
184-476 5.98e-74

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: 237.80  E-value: 5.98e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVL---YSGATLDEAERLTEEE 260
Cdd:cd15267    3 YSSFQVMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASSVLVIDGLLrtrYSQKIEDDLSSTWLSD 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 261 lraiaqappppataaAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWV 340
Cdd:cd15267   83 ---------------EAVAGCRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPALFVVPWV 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 341 SVRATLANTGCWDLS-SGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRqqyRKLLKSTLVLMPLFGV 419
Cdd:cd15267  148 VVKCLYENVQCWTSNdNMGFWWILRFPVFLAILINFFIFVRIIQILVSKLRARQMHYTDYK---FRLAKSTLTLIPLLGI 224
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 296080761 420 HYIVFMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15267  225 HEVVFAFVTDEHAQGTLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHR 281
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
189-476 6.04e-73

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: 234.62  E-value: 6.04e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 189 MIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLysgatldeAERLTEEElraiaqap 268
Cdd:cd15264    6 IIYYLGFSISLVALAVALIIFLYFRSLRCLRNNIHCNLIVTFILRNVTWFIMQNTL--------TEIHHQSN-------- 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 269 pppataaagYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLAN 348
Cdd:cd15264   70 ---------QWVCRLIVTVYNYFQVTNFFWMFVEGLYLHTMIVWAYSADKIRFWYYIVIGWCIPCPFVLAWAIVKLLYEN 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 349 TGCWDLSSGNKK--WIIQVPILASIVLNFILFINIVRVLATKLRETNAgrcDTRQQYRKLLKSTLVLMPLFGVHYIVFMA 426
Cdd:cd15264  141 EHCWLPKSENSYydYIYQGPILLVLLINFIFLFNIVWVLITKLRASNT---LETIQYRKAVKATLVLLPLLGITYMLFFI 217
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 296080761 427 TPytEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15264  218 NP--GDDKTSRLVFIYFNTFLQSFQGLFVAVFYCFLNGEVRSAIRKKFSR 265
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
187-476 1.38e-69

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: 226.37  E-value: 1.38e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVL---YSGATLDEAerlteeelra 263
Cdd:cd15268    4 LYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALkwmYSTAAQQHQ---------- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 iaqapPPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR 343
Cdd:cd15268   74 -----WDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFVIPWGIVK 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKW-IIQVPILASIVLNFILFINIVRVLATKLRETNAgrCDTRQQYRkLLKSTLVLMPLFGVHYI 422
Cdd:cd15268  149 YLYEDEGCWTRNSNMNYWlIIRLPILFAIGVNFLIFIRVICIVVSKLKANLM--CKTDIKCR-LAKSTLTLIPLLGTHEV 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 296080761 423 VFMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15268  226 IFAFVMDEHARGTLRFVKLFTELSFTSFQGLMVAILYCFVNNEVQMEFRKSWER 279
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
189-476 9.10e-69

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: 223.69  E-value: 9.10e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 189 MIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSifvkdAVLYSGATLDEAERLTEEELRaiaqap 268
Cdd:cd15260    6 YVYIGGYSVSLIALIISLAIFFSFRSLRCTRITIHMNLFISFALNNLL-----WIVWYKLVVDNPEVLLENPIW------ 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 269 pppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATL-- 346
Cdd:cd15260   75 ------------CQALHVLLQYFMVCNYFWMFCEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLpd 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 347 ANTGCWdLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRcdTRQQYRKLLKSTLVLMPLFGVHYIVFMA 426
Cdd:cd15260  143 DTERCW-MEESSYQWILIVPVVLSLLINLIFLINIVRVLLTKLRATSPNP--APAGLRKAVRATLILIPLLGLQFLLIPF 219
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 296080761 427 TPytEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15260  220 RP--EPGAPLETIYQYVSALLTSLQGLCVAVLFCFCNGEVIAAIKRKWRR 267
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
193-482 5.35e-65

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: 213.87  E-value: 5.35e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 193 VGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTeeelraiaqappppa 272
Cdd:cd15274   10 VGHSLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSIIIIIHLVAVVPNGELVARNPVS--------------- 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 273 taaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANTGCW 352
Cdd:cd15274   75 --------CKILHFIHQYMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAITRAVYYNDNCW 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 353 DLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCdtrQQYRKLLKSTLVLMPLFGVHYIVFMATPYTEV 432
Cdd:cd15274  147 LSSETHLLYIIHGPIMAALVVNFFFLLNIVRVLVTKLRETHEAES---HMYLKAVKATLILVPLLGIQFVLFPWRPSGKI 223
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 296080761 433 SGTLWQVQMHYEMlfnSFQGFFVAIIYCFCNGEVQAEIKKSWSRWTLALD 482
Cdd:cd15274  224 LGKIYDYVMHSLI---HFQGFFVATIFCFCNGEVQATLKRQWNQYKIQFG 270
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
187-470 2.68e-64

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: 211.69  E-value: 2.68e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSgatldeaerlteeelraiaq 266
Cdd:cd13952    4 LSIITYIGCSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLLTSS-------------------- 63
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFF-SEKKYLWGFTVFGWGLPAVFVAVWVSVRAT 345
Cdd:cd13952   64 ---------DRPVLCKALAILLHYFLLASFFWMLVEAFDLYRTFVKVFGsSERRRFLKYSLYGWGLPLLIVIITAIVDFS 134
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 346 LA-------NTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNagRCDTRQQYRKLLKSTLVLMPLFG 418
Cdd:cd13952  135 LYgpspgygGEYCWLSNGNALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETP--KQSERKSDRKQLRAYLKLFPLMG 212
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 296080761 419 VHYIVFMATPYTEVSGTLWQVqmhyEMLFNSFQGFFVAIIYCFCNGEVQAEI 470
Cdd:cd13952  213 LTWIFGILAPFVGGSLVFWYL----FDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
189-476 9.35e-57

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: 192.20  E-value: 9.35e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 189 MIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSgatldeaerlteeelraiaqap 268
Cdd:cd15263    6 TIYFIGYSLSLVALSLALWIFLYFKDLRCLRNTIHTNLMFTYILADLTWILTLTLQVS---------------------- 63
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 269 pppatAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRA---T 345
Cdd:cd15263   64 -----IGEDQKSCIILVVLLHYFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYAFIGWGIPAVVIVIWAIVKAlapT 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 346 LANTG---------CWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAgrCDTrQQYRKLLKSTLVLMPL 416
Cdd:cd15263  139 APNTAldpngllkhCPWMAEHIVDWIFQGPAILVLAVNLVFLVRIMWVLITKLRSANT--VET-QQYRKAAKALLVLIPL 215
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 417 FGVHYIVFMATPYTEVSGTLWQvqmHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15263  216 LGITYILVIAGPTEGIAANIFE---YVRAVLLSTQGFTVALFYCFLNTEVRNTLRHHFER 272
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
193-476 2.58e-53

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: 183.34  E-value: 2.58e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 193 VGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSfMLRAVSIFVkdaVLYsgatLDEAerLTEEELRAIAQAPPPPA 272
Cdd:cd15261   10 VGLCLSLVSLIISLFIFSYFRTLRNHRTRIHKNLFLA-ILLQVIIRL---VLY----IDQA--ITRSRGSHTNAATTEGR 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 273 TAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANTG-C 351
Cdd:cd15261   80 TINSTPILCEGFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAIVTLIKMKVNrC 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 352 WDLSSGNKK-WIIQVPILASIVLNFILFINIVRVLATKLRETNagrCDTRQQYRKLLKSTLVLMPLFGVHYIVFMATPYT 430
Cdd:cd15261  160 WFGYYLTPYyWILEGPRLAVILINLFFLLNIIRVLVSKLRESH---SREIEQVRKAVKAAIVLLPLLGITNILQMIPPPL 236
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 296080761 431 EVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15261  237 TSVIVGFAVWSYSTHFLTSFQGFFVALIYCFLNGEVKNVLKKFWRR 282
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
189-476 3.54e-47

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: 166.29  E-value: 3.54e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 189 MIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAerlteeelraiaqap 268
Cdd:cd15446    6 IINYLGHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFLLQMIDHNIHESNEV--------------- 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 269 pppataaagyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLAN 348
Cdd:cd15446   71 -----------WCRCITTIYNYFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYEN 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 349 TGCWDLSSGNK--KWIIQVPILASIVLNFILFINIVRVLATKLRetnAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVFMA 426
Cdd:cd15446  140 EQCWFGKEPGKyiDYIYQGPVILVLLINFVFLFNIVRILMTKLR---ASTTSETIQYRKAVKATLVLLPLLGITYMLFFV 216
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 296080761 427 TPYTEVSGTLwqVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15446  217 NPGEDDISQI--VFIYFNSFLQSFQGFFVSVFYCFLNGEVRSAARKRWHR 264
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
191-476 4.57e-46

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: 163.39  E-value: 4.57e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 191 YTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAV-SIFVKDAVLYSGATLDEAER-LTEEELraiaqap 268
Cdd:cd15262    8 HVAALSVSVVTSLPAVFIFYSYKRLRITRVILHRNLLISIIIRNIlVIISKVFVILDALTSSGDDTvMNQNAV------- 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 269 pppataaagyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIfMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLAN 348
Cdd:cd15262   81 -----------VCRLLSIFERAARNAVFACMFVEGFYLHRLI-VAVFAEKSSIRFLYVIGAVLPLFPVIIWAIIRALHND 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 349 TGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNagrcdTRQQYRKLLKSTLVLMPLFGVHYIVfmaTP 428
Cdd:cd15262  149 HSCWVVDIEGVQWVLDTPRLFILLVNTVLLVDIIRVLVTKLRNTE-----ENSQTKSTTRATLFLVPLFGLHFVI---TA 220
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 296080761 429 YTEVSGTLWQVQMHY--EMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15262  221 YRPSTDDCDWEDIYYyaNYLIEGLQGFLVAILFCYINKEVHYLIKNTYRK 270
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
189-476 5.62e-46

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: 163.18  E-value: 5.62e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 189 MIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGAtldeaerlteeelraiaqap 268
Cdd:cd15445    6 IINYLGHCISLVALLVAFVLFLRLRSIRCLRNIIHWNLITAFILRNATWFVVQLTMSPEV-------------------- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 269 pppatAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLAN 348
Cdd:cd15445   66 -----HQSNVVWCRLVTAAYNYFHVTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFICIGWCIPFPIIVAWAIGKLYYDN 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 349 TGCWdlsSGNK-----KWIIQVPILASIVLNFILFINIVRVLATKLRetnAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15445  141 EKCW---FGKRagvytDYIYQGPMILVLLINFIFLFNIVRILMTKLR---ASTTSETIQYRKAVKATLVLLPLLGITYML 214
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 296080761 424 FMATP-YTEVSGTLWqvqMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15445  215 FFVNPgEDEISRIVF---IYFNSFLESFQGFFVSVFYCFLNSEVRSAVRKRWHR 265
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
193-467 5.88e-28

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: 112.67  E-value: 5.88e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 193 VGYSVSLASLTVAVLILAYFRRLHCT-RNYIHMHLflsfmlrAVSIFVKDAVLYSGATLDEAErlteeelraiaqapppp 271
Cdd:cd15040   10 IGCGLSLLGLLLTIITYILFRKLRKRkPTKILLNL-------CLALLLANLLFLFGINSTDNP----------------- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 272 ataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAF-FSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANTG 350
Cdd:cd15040   66 -------VLCTAVAALLHYFLLASFMWMLVEALLLYLRLVKVFgTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNS 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 351 ---CWdLSSGNK-KWIIQVPILASIVLNFILFINIVRVLATKLRETNAgrcDTRQQYRKLLKSTLVLMPLFGVHYIVFMA 426
Cdd:cd15040  139 sgyCW-LSNGNGlYYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNK---KKRKKTKAQLRAAVSLFFLLGLTWIFGIL 214
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 296080761 427 TPYTEvsgtlwQVQMHYE-MLFNSFQGFFVAIIYCFCNGEVQ 467
Cdd:cd15040  215 AIFGA------RVVFQYLfAIFNSLQGFFIFIFHCLRNKEVR 250
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
187-468 1.17e-26

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: 108.95  E-value: 1.17e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIfvkdaVLYSGATLDEAerlteeelraiaq 266
Cdd:cd15933    4 LSIISYIGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILL-----LAGEWAEGNKV------------- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIfMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVR--A 344
Cdd:cd15933   66 -------------ACKVVAILLHFFFMAAFSWMLVEGLHLYLMI-VKVFNYKSKMRYYYFIGWGLPAIIVAISLAILfdD 131
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 345 TLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVF 424
Cdd:cd15933  132 YGSPNVCWLSLDDGLIWAFVGPVIFIITVNTVILILVVKITVSLSTNDAKKSQGTLAQIKSTAKASVVLLPILGLTWLFG 211
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 296080761 425 MATPyteVSGTlwqVQMHYemLF---NSFQGFFVAIIYCFCNGEVQA 468
Cdd:cd15933  212 VLVV---NSQT---IVFQY--IFvilNSLQGLMIFLFHCVLNSEVRS 250
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
187-472 9.25e-26

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


Pssm-ID: 320556 [Multi-domain]  Cd Length: 259  Bit Score: 106.58  E-value: 9.25e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSfmlravsIFVKDAVLYSGATLdeaerlTEEELraiaq 266
Cdd:cd15440    4 LTFITYIGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLCLC-------LLIAEIVFLLGIDQ------TENRT----- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATL 346
Cdd:cd15440   66 -------------LCGVIAGLLHYFFLAAFSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLFGYGLPALIVAVSAGVDPTG 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 347 ANTG--CWDLSSGNKKWIIQVPILASIVLNFI-LFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIV 423
Cdd:cd15440  133 YGTEdhCWLSTENGFIWSFVGPVIVVLLANLVfLGMAIYVMCRHSSRSASKKDASKLKNIRGWLKGSIVLVVLLGLTWTF 212
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 296080761 424 fmatpytevsGTLWQVQ----MHYemLF---NSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd15440  213 ----------GLLFINQesivMAY--IFtilNSLQGLFIFIFHCVLNEKVRKELRR 256
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
105-173 2.70e-24

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: 95.90  E-value: 2.70e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 296080761  105 GRPCLPEWDHILCWPLGAPGEVVAVPCPDYIYDFNHKGHAYRRCDRNGSWELVPGHnrtwaNYSECVKF 173
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDPRGNASRNCTEDGTWSEHPPS-----NYSNCTSN 64
HormR smart00008
Domain present in hormone receptors;
105-179 6.18e-22

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 89.50  E-value: 6.18e-22
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296080761   105 GRPCLPEWDHILCWPLGAPGEVVAVPCPDYIYDFNHKGHAYRRCDRNGSWElvpghnRTWANYSECVKFLTNETR 179
Cdd:smart00008   2 DLGCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTGASRNCTENGGWS------PPFPNYSNCTSNDYEELK 70
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
187-471 2.47e-18

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: 84.98  E-value: 2.47e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNY-IHMHLFLSFMLRAVSIFVKDAVLYSGATLDeaerlteeelraia 265
Cdd:cd15256    4 LSSITYVGCSLSIFCLAITLVTFAVLSSVSTIRNQrYHIHANLSFAVLVAQILLLISFRFEPGTLP-------------- 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 266 qappppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVF--VAVWVSVR 343
Cdd:cd15256   70 ---------------CKIMAILLHFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGIGWGSPLLIciISLTSALD 134
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 ATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTrQQYRKLLKSTLVLMPLFGVHYI- 422
Cdd:cd15256  135 SYGESDNCWLSLENGAIWAFVAPALFVIVVNIGILIAVTRVISRISADNYKVHGDA-NAFKLTAKAVAVLLPILGSSWVf 213
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 296080761 423 -VFMATPYTEVSGTLWQVqmhyemlFNSFQGFFVAIIYCFCNGEVQAEIK 471
Cdd:cd15256  214 gVLAVNTHALVFQYMFAI-------FNSLQGFFIFLFHCLLNSEVRAAFK 256
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
193-476 1.47e-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: 79.60  E-value: 1.47e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 193 VGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGATLdeaerlTEEELRaiaqappppa 272
Cdd:cd15441   10 IGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNL-------VACLLLAELLFLLGINQ------TENLFP---------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 273 taaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIF---------MAFFsekkYLwgftvFGWGLPAVFVAVWVSVR 343
Cdd:cd15441   67 --------CKLIAILLHYFYLSAFSWLLVESLHLYRMLTeprdinhghMRFY----YL-----LGYGIPAIIVGLSVGLR 129
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 344 A-TLANTG-CWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKlretnaGRCDTRQQ-YRKLLKSTLVLMPLFGVh 420
Cdd:cd15441  130 PdGYGNPDfCWLSVNETLIWSFAGPIAFVIVITLIIFILALRASCTL------KRHVLEKAsVRTDLRSSFLLLPLLGA- 202
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 296080761 421 yivfmatpyTEVSGTLwQVQMHYEML------FNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15441  203 ---------TWVFGLL-AVNEDSELLhylfagLNFLQGLFIFLFYCIFNKKVRRELKNALLR 254
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
187-472 4.35e-16

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: 78.54  E-value: 4.35e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGatLDEaerlTEEELraiaq 266
Cdd:cd15439    4 LTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQL-------SLCLFLADLLFLVG--IDR----TDNKV----- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyaGCRVAVTFFLY-FLATnYYWILVEGLYLH----SLIFMAFFSEKKYL-WGFTVFGWGLPAVFVAVWV 340
Cdd:cd15439   66 -------------LCSIIAGFLHYlFLAC-FAWMFLEAVHLFltvrNLKVVNYFSSHRFKkRFMYPVGYGLPAVIVAISA 131
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 341 SVRATLANTG--CWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAgRCDTRQQYRKLLKSTLVLMPLFG 418
Cdd:cd15439  132 AVNPQGYGTPkhCWLSMEKGFIWSFLGPVCVIIVINLVLFCLTLWILREKLSSLNA-EVSTLKNTRLLTFKAIAQLFILG 210
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 296080761 419 VHYIV--FMATPYTEVSGTLWQVqmhyemlFNSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd15439  211 CTWILglFQVGPVATVMAYLFTI-------TNSLQGVFIFLVHCLLNRQVREEYRR 259
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
187-477 3.47e-15

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: 75.95  E-value: 3.47e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSfmlravsIFVKDAVLYSGATLDEAErlteeelraiaq 266
Cdd:cd15438    4 LTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLS-------LFLAHLIFLLGINNTNNQ------------ 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATL 346
Cdd:cd15438   65 ------------VACAVVAGLLHYFFLAAFCWMSLEGVELYLMVVQVFNTQSLKKRYLLLIGYGVPLVIVAISAAVNSKG 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 347 ANT--GCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAgRCDTRQQYRKLLKSTLVLMPLFGVHYIVF 424
Cdd:cd15438  133 YGTqrHCWLSLERGFLWSFLGPVCLIILVNAIIFVITVWKLAEKFSSINP-DMEKLRKIRALTITAIAQLCILGCTWIFG 211
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 296080761 425 MatpYTEVSGTLWqvqMHYEM-LFNSFQGFFVAIIYCFCNGEVQAEikksWSRW 477
Cdd:cd15438  212 F---FQFSDSTLV---MSYLFtILNSLQGLFIFLLHCLLSKQVREE----YSRW 255
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
187-472 2.32e-14

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: 73.31  E-value: 2.32e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGATLDEAERLteeelraiaq 266
Cdd:cd15252    4 LTRITQVGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNL-------CISLFLAELVFLIGINTTTNKIF---------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSV--RA 344
Cdd:cd15252   67 --------------CSVIAGLLHYFFLAAFAWMFIEGIQLYLMLVEVFENEGSRHKNFYIFGYGSPAVIVGVSAALgyRY 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 345 TLANTGCWDLSSGNKKWIIQVPILASIVLNFILF-INIVRVLA-TKLRETNAGRCDTrqqYRKLLKSTLVLMPLFGVHYI 422
Cdd:cd15252  133 YGTTKVCWLSTENYFIWSFIGPATLIILLNLIFLgVAIYKMFRhTAGLKPEVSCLEN---IRSWARGAIALLFLLGLTWI 209
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 296080761 423 V-FMATPYTEVsgtlwqVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd15252  210 FgVLHINHASV------VMAYLFTVSNSLQGMFIFLFHCVLSRKVRKEYYK 254
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
187-471 3.49e-13

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: 70.03  E-value: 3.49e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRlHCTRNYI-HM-HLFLSFMlrAVSIFVKDAVLYSGATLDEAERLTeeelrai 264
Cdd:cd15932    4 LDYITYVGLGISILSLVLCLIIEALVWK-SVTKNKTsYMrHVCLVNI--ALSLLIADIWFIIGAAISTPPNPS------- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 265 aqappppataaagyAGCrVAVTFFLYF--LATnYYWILVEGLYLHSLIFMAFFSEKKYLW---GFTVfGWGLPAVFVAVW 339
Cdd:cd15932   74 --------------PAC-TAATFFIHFfyLAL-FFWMLTLGLLLFYRLVLVFHDMSKSTMmaiAFSL-GYGCPLIIAIIT 136
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 340 VSV----RATLANTGCW-DLSSGNKKWIIQVPILASIVLNFIlfinIVRVLATKLRETNAGRCDTRQQYRKLL---KSTL 411
Cdd:cd15932  137 VAAtapqGGYTRKGVCWlNWDKTKALLAFVIPALAIVVVNFI----ILIVVIFKLLRPSVGERPSKDEKNALVqigKSVA 212
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 296080761 412 VLMPLFGVHYIVFMATPYTEVSGTLwqvqmHYEM-LFNSFQGFFVAIIYCFCNGEVQAEIK 471
Cdd:cd15932  213 ILTPLLGLTWGFGLGTMIDPKSLAF-----HIIFaILNSFQGFFILVFGTLLDSKVREALL 268
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
283-476 7.73e-12

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


Pssm-ID: 320381 [Multi-domain]  Cd Length: 271  Bit Score: 65.94  E-value: 7.73e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 283 VAVTFFLYF--LATnYYWILVEGLYL-HSLIFMAFFSEKKYLWGFTVF-GW----GLPAVFVAVWVSVRATLANTGCWDL 354
Cdd:cd15253   76 LAAAFLCHFfyLAT-FFWMLVQALMLfHQLLFVFHQLAKRSVLPLMVTlGYlcplLIAAATVAYYYPKRQYLHEGACWLN 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 355 SSGNKKWIIQVPILASIVLNF-ILFINIVRVLATKLRETNagRCDTRQQYRKLLKSTLVLMPLFGVHYIVFMATPYTEVS 433
Cdd:cd15253  155 GESGAIYAFSIPVLAIVLVNLlVLFVVLMKLMRPSVSEGP--PPEERKALLSIFKALLVLTPVFGLTWGLGVATLTGESS 232
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 296080761 434 gtlwQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15253  233 ----QVSHYGFAILNAFQGVFILLFGCLMDKKVREALLKRLCK 271
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
187-469 1.03e-11

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: 65.51  E-value: 1.03e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLhcTRNY---IHMHLFLSFMLRAVSIFVKDAVLYSGatldeaerlteeelra 263
Cdd:cd15258    4 LTFISYVGCGISAIFLAITILTYIAFRKL--RRDYpskIHMNLCAALLLLNLAFLLSSWIASFG---------------- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 264 iaqappppataaaGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTVFGWGLPAVFVAVWVSV 342
Cdd:cd15258   66 -------------SDGLCIAVAVALHYFLLACLTWMGLEAFHLYLLLVKVFNTYiRRYILKLCLVGWGLPALLVTLVLSV 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 343 RATLANTgCWDLSSGNKK-----WIIQVPILASIVLNF---ILFINIVR---VLATKLRETNAGRCDTRQQYRKLLKSTL 411
Cdd:cd15258  133 RSDNYGP-ITIPNGEGFQndsfcWIRDPVVFYITVVGYfglTFLFNMVMlatVLVQICRLREKAQATPRKRALHDLLTLL 211
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 296080761 412 VLMPLFGVHYIVFMATPytevsGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAE 469
Cdd:cd15258  212 GLTFLLGLTWGLAFFAW-----GPFNLPFLYLFAIFNSLQGFFIFIWYCSMKENVRKQ 264
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
283-472 2.22e-11

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: 64.49  E-value: 2.22e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 283 VAVTFFLY-FLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWV--SVRATLANTGCWDLSSGNK 359
Cdd:cd15255   68 WAVTALLHlFFLAAFSWMLVEGLLLWSKVVAVNMSEDRRMKFYYVTGWGLPVVIVAVTLatSFNKYVADQHCWLNVQTDI 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 360 KWIIQVPILASIVLNFILFINIVRVLATKLRETN---AGRCDTRQQYRKLL----KSTLVLMPLFGVhyivfmatpyTEV 432
Cdd:cd15255  148 IWAFVGPVLFVLTVNTFVLFRVVMVTVSSARRRAkmlTPSSDLEKQIGIQIwataKPVLVLLPVLGL----------TWL 217
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 296080761 433 SGTLWQVQMHYEMLF---NSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd15255  218 CGVLVHLSDVWAYVFitlNSFQGLYIFLVYAIYNSEVRNAIQR 260
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
190-463 4.01e-11

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: 63.99  E-value: 4.01e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 190 IYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVkdAVLYSGATLDeaerlteeelraiaqapp 269
Cdd:cd14964    4 ILSLLTCLGLLGNLLVLLSLVRLRKRPRSTRLLLASLAACDLLASLVVLV--LFFLLGLTEA------------------ 63
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 270 ppatAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLI-----FMAFFSEKKYLWgFTVFGWGLPAVFVAVWVSVRA 344
Cdd:cd14964   64 ----SSRPQALCYLIYLLWYGANLASIWTTLVLTYHRYFALcgplkYTRLSSPGKTRV-IILGCWGVSLLLSIPPLVGKG 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 345 TLANTGCWDLSSGNKKWIIQVPILASIVLNF-----ILFINIVRVLATKLRETNAGRCDTRQQYR--KLLKSTLVLMPLF 417
Cdd:cd14964  139 AIPRYNTLTGSCYLICTTIYLTWGFLLVSFLlplvaFLVIFSRIVLRLRRRVRAIRSAASLNTDKnlKATKSLLILVITF 218
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 296080761 418 GVHYIVFmatPYTEVSGTLWQ--VQMHYE----MLFNSFQGFFVAIIYCFCN 463
Cdd:cd14964  219 LLCWLPF---SIVFILHALVAagQGLNLLsilaNLLAVLASTLNPFIYCLGN 267
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
187-472 5.40e-11

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: 63.30  E-value: 5.40e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGatldeaERLTEEELRaiaq 266
Cdd:cd15931    4 LEWINRVGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHL-------CLCLSMSHTLFLAG------IEYVENELA---- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEK------KYLWgFTVFGWGLPAVFVAVWV 340
Cdd:cd15931   67 --------------CTVMAGLLHYLFLASFVWMLLEALQLHLLVRRLTKVQViqrdglPRPL-LCLIGYGVPFLIVGVSA 131
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 341 SVRAT---LANTgCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAgRCDTRQQYRKLLKSTLVLMPLF 417
Cdd:cd15931  132 LVYSDgygEAKM-CWLSQERGFNWSFLGPVIAIIGINWILFCATLWCLRQTLSNMNS-DISQLKDTRLLTFKAVAQLFIL 209
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 296080761 418 GVHYI--VFMATPYTEVSGTLWqvqmhyeMLFNSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd15931  210 GCTWVlgLFQTNPVALVFQYLF-------TILNSLQGAFLFLVHCLLNKEVREEYIK 259
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
187-472 3.40e-10

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


Pssm-ID: 320672 [Multi-domain]  Cd Length: 258  Bit Score: 61.08  E-value: 3.40e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGATLDEAErlteeelraiaq 266
Cdd:cd16006    4 LTVITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNL-------CINLFIAEFIFLIGIDKTEYK------------ 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSL---IFMAFFSEKKYlwgFTVFGWGLPAVFVAVWVSV- 342
Cdd:cd16006   65 ------------IACPIFAGLLHFFFLAAFAWMCLEGVQLYLMlveVFESEYSRKKY---YYVAGYLFPATVVGVSAAId 129
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 343 -RATLANTGCWDLSSGNKKWIIQVPILASIVLNFILfinIVRVLATKLRETNAGRCDTRQ--QYRKLLKSTLVLMPLFGV 419
Cdd:cd16006  130 yKSYGTEKACWLRVDNYFIWSFIGPVTFIILLNLIF---LVITLCKMVKHSNTLKPDSSRleNIKSWVLGAFALLCLLGL 206
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 296080761 420 HY---IVFMATPYTevsgtlwqVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd16006  207 TWsfgLLFINEETI--------VMAYLFTIFNAFQGMFIFIFHCALQKKVRKEYSK 254
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
187-472 1.20e-09

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: 59.17  E-value: 1.20e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGatLDEaerlTEEELraiaq 266
Cdd:cd16007    4 LSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNL-------CINLFLAELLFLIG--IDK----TQYQI----- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAF---FSEKKYlwgFTVFGWGLPAVFVAVWVSV- 342
Cdd:cd16007   66 -------------ACPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVEVFeseYSRKKY---YYLCGYCFPALVVGISAAId 129
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 343 -RATLANTGCWDLSSGNKKWIIQVPILASIVLNFI-LFINIVRVL-ATKLRETNAGRCDTRQQYRKLLKSTLVLMPL--- 416
Cdd:cd16007  130 yRSYGTEKACWLRVDNYFIWSFIGPVSFVIVVNLVfLMVTLHKMIrSSSVLKPDSSRLDNIKSWALGAITLLFLLGLtwa 209
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 417 FGVHYI----VFMATPYTevsgtlwqvqmhyemLFNSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd16007  210 FGLLFInkesVVMAYLFT---------------TFNAFQGMFIFIFHCALQKKVHKEYSK 254
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
281-477 2.48e-09

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


Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 58.68  E-value: 2.48e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 281 CRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTVFGWGLPAVFVAVWVSVRATLANTGCW------- 352
Cdd:cd15444   71 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVAIVLAVSKDNYGLGSYgkspngs 150
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 353 --DLSSGNKKWIIQVPILASIVLNFILFINIVRVLATKL------RETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVF 424
Cdd:cd15444  151 tdDFCWINNNIVFYITVVGYFCVIFLLNISMFIVVLVQLcrikkqKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAW 230
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296080761 425 matpytevsGTLWQVQMHYEMLFNSFQGFFVAIIYCFcngeVQAEIKKSWSRW 477
Cdd:cd15444  231 ---------GPVNLAFMYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRRY 270
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
187-472 9.88e-09

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


Pssm-ID: 320552 [Multi-domain]  Cd Length: 258  Bit Score: 56.34  E-value: 9.88e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFlsfmlraVSIFVKDAVLYSGATLDEAErlteeelraiaq 266
Cdd:cd15436    4 LFVITWVGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLC-------INLFIAELLFLIGINRTQYT------------ 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSL---IFMAFFSEKKYlwgFTVFGWGLPAVFVAVWVSV- 342
Cdd:cd15436   65 ------------IACPIFAGLLHFFFLAAFCWLCLEGVQLYLLlveVFESEYSRRKY---FYLCGYSFPALVVAVSAAId 129
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 343 -RATLANTGCWDLSSGNKKWIIQVPILASIVLNFI-LFINIVRVLAT-KLRETNAGRCDTRQQYRKLLKSTLVLMPL--- 416
Cdd:cd15436  130 yRSYGTEKACWLRVDNYFIWSFIGPVTFVITLNLVfLVITLHKMVSHsDLLKPDSSRLDNIKSWALGAIALLFLLGLtws 209
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 417 FGVHYI----VFMATPYTevsgtlwqvqmhyemLFNSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd15436  210 FGLMFIneesVVMAYLFT---------------IFNAFQGVFIFIFHCALQKKVRKEYSK 254
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
185-475 1.04e-08

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: 56.47  E-value: 1.04e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 185 DRLGMIYTVGYSVSLASLTVAVLILAYFRRLhctRNyIHMHLFLSFMlraVSIFVKDAVLYSGAtldeaerlteeelrai 264
Cdd:cd15039    2 SILGILTLIGLIISLVFLLLTLAVYALLPEL---RN-LHGKCLMCLV---LSLFVAYLLLLIGQ---------------- 58
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 265 aqappppATAAAGYAGCrVAVTFFLYF--LATnYYWILVEGLYLH-----SLIFMAFFSEKKYLWGFTVFGWGLPAVFVA 337
Cdd:cd15039   59 -------LLSSGDSTLC-VALGILLHFffLAA-FFWLNVMSFDIWrtfrgKRSSSSRSKERKRFLRYSLYAWGVPLLLVA 129
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 338 V---------WVSVRATLANTGCWdLSSGNKKWII-QVPILASIVLNFILFINIVRVLATKLRETN---AGRCDTRQQYR 404
Cdd:cd15039  130 VtiivdfspnTDSLRPGYGEGSCW-ISNPWALLLYfYGPVALLLLFNIILFILTAIRIRKVKKETAkvqSRLRSDKQRFR 208
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 296080761 405 KLLKSTlVLMplfGVHYIVFMATPYTEVSGTLWQVQmhyeMLFNSFQGFFVAIIYCfCNGEVQAEIKKSWS 475
Cdd:cd15039  209 LYLKLF-VIM---GVTWILEIISWFVGGSSVLWYIF----DILNGLQGVFIFLIFV-CKRRVLRLLKKKIR 270
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
187-472 1.77e-08

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: 55.72  E-value: 1.77e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGATLDEAErlteeelraiaq 266
Cdd:cd16005    4 LDVITWVGILLSLVCLLICIFTFCFFRGLQSDRNTIHKNL-------CISLFVAELLFLIGINRTDQP------------ 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSV--RA 344
Cdd:cd16005   65 ------------IACAVFAALLHFFFLAAFTWMFLEGVQLYIMLVEVFESEHSRRKYFYLVGYGMPALIVAVSAAVdyRS 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 345 TLANTGCWDLSSGNKKWIIQVPILASIVLNFI-LFINIVRVL-ATKLRETNAGRCDTRQQYRKLLKSTLVLMPL---FGV 419
Cdd:cd16005  133 YGTDKVCWLRLDTYFIWSFIGPATLIIMLNVIfLGIALYKMFhHTAILKPESGCLDNIKSWVIGAIALLCLLGLtwaFGL 212
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 296080761 420 HYI----VFMATPYTevsgtlwqvqmhyemLFNSFQGFFVAIIYCFCNGEVQAEIKK 472
Cdd:cd16005  213 MYInestVIMAYLFT---------------IFNSLQGMFIFIFHCVLQKKVRKEYGK 254
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
187-476 1.79e-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: 55.65  E-value: 1.79e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGATLDEAERLteeelraiaq 266
Cdd:cd15437    4 LTRITQLGIIISLICLSMCIFTFWFFSEIQSTRTTIHKNL-------CCSLFLAELIFLIGINMNANKLF---------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHsLIFMAFFSEKKYLW-GFTVFGWGLPAVFVAVWVSVRAT 345
Cdd:cd15437   67 --------------CSIIAGLLHYFFLAAFAWMCIEGIHLY-LIVVGVIYNKGFLHkNFYIFGYGSPAVVVGISAALGYK 131
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 346 LANTG--CWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLatkLRETNAGRCDTR--QQYRKLLKSTLVLMPLFGVHY 421
Cdd:cd15437  132 YYGTTkvCWLSTENNFIWSFIGPACLIILVNLLAFGVIIYKV---FRHTAMLKPEVScyENIRSCARGALALLFLLGATW 208
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 296080761 422 I--VFMATPYTEVSGTLWQVqmhyemlFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 476
Cdd:cd15437  209 IfgVLHVVYGSVVTAYLFTI-------SNAFQGMFIFIFLCVLSRKIQEEYYRLFKN 258
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
281-474 2.06e-08

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: 55.82  E-value: 2.06e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 281 CRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTVFGWGLPAVFVAVWVSVRATLANTG--------- 350
Cdd:cd15997   70 CITVAAFLHYFLLASFTWMGLEAVHMYFALVKVFNIYiPNYILKFCIAGWGIPAVVVALVLAINKDFYGNElssdslhps 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 351 ---CWDlssgNKKWIIQVPILASIVLnfILFINIVrVLATKLRETNAGRCDTRQQYRKL-----LKSTLVLMPLFGVHYI 422
Cdd:cd15997  150 tpfCWI----QDDVVFYISVVAYFCL--IFLCNIS-MFITVLIQIRSMKAKKPSRNWKQgflhdLKSVASLTFLLGLTWG 222
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296080761 423 -VFMATpytevsGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQaeikKSW 474
Cdd:cd15997  223 fAFFAW------GPVRIFFLYLFSICNTLQGFFIFVFHCLMKENVR----KQW 265
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
187-476 3.15e-08

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


Pssm-ID: 320385 [Multi-domain]  Cd Length: 303  Bit Score: 55.65  E-value: 3.15e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRN-------YIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEE 259
Cdd:cd15257    4 LDIISTIGCVLSIAGLVITIIFHLHTRKLRKSSVtwvllnlCSSLLLFNIIFTSGVENTNNDYEISTVPDRETNTVLLSE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 260 ElraiaqappppatAAAGYAGCRVAVTFFL-YFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGF-TVFGWGLPAVFVA 337
Cdd:cd15257   84 E-------------YVEPDTDVCTAVAALLhYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQaSAIGWGIPAVVVA 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 338 VW--VSVRATLANTG----------CWdLSSGNKKWIIQVPILASIVL--------NFILFINIvrvLATKLRETNAGRC 397
Cdd:cd15257  151 ITlgATYRFPTSLPVftrtyrqeefCW-LAALDKNFDIKKPLLWGFLLpvglilitNVILFIMT---SQKVLKKNNKKLT 226
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 398 DTRQQYRKLLKSTLVLMPLFGVHYIV--FMATpyteVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWS 475
Cdd:cd15257  227 TKKRSYMKKIYITVSVAVVFGITWILgyLMLV----NNDLSKLVFSYIFCITNTTQGVQIFILYTWRTPEFRKLVSKLSL 302

                 .
gi 296080761 476 R 476
Cdd:cd15257  303 K 303
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
187-471 7.03e-08

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


Pssm-ID: 320657 [Multi-domain]  Cd Length: 254  Bit Score: 54.08  E-value: 7.03e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGATLDEAERLteeelraiaq 266
Cdd:cd15991    4 LKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNL-------VAALFFSELIFLIGINQTENPFV---------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVF--VAVWVSVRA 344
Cdd:cd15991   67 --------------CTVVAILLHYFYMSTFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPAIItgLAVGLDPQG 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 345 TLANTGCWDLSSGNKKWIIQVPILASIVLNFILFInivrvLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVF 424
Cdd:cd15991  133 YGNPDFCWLSVQDTLIWSFAGPIGIVVIINTVIFV-----LAAKASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLG 207
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 296080761 425 MATPYTEVsgtlwqVQMHYEM-LFNSFQGFFVAIIYCFCNGEVQAEIK 471
Cdd:cd15991  208 LMAVNSDT------LSFHYLFaIFSCLQGIFIFFFHCIFNKEVRKHLK 249
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
281-476 1.24e-07

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


Pssm-ID: 320662  Cd Length: 271  Bit Score: 53.35  E-value: 1.24e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 281 CRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTVFGWGLPAVFVAVWVSVRATLANTGCWDLSSGNK 359
Cdd:cd15996   70 CITVAVLLHFFLLATFTWMGLEAIHMYIALVKVFNTYiRRYILKFCIIGWGLPALIVSIVLASTNDNYGYGYYGKDKDGQ 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 360 K-----WIIQ-----VPILASIVLNFILFINIVRVLATKLRETNAGRCD--TRQQYRKLLKSTLVLMPLFGVHY-IVFMA 426
Cdd:cd15996  150 GgdefcWIKNpvvfyVTCAAYFGIMFLMNVAMFIVVMVQICGRNGKRSNrtLREEILRNLRSVVSLTFLLGMTWgFAFFA 229
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 296080761 427 TpytevsGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQaeikKSWSR 476
Cdd:cd15996  230 W------GPVNLAFMYLFTIFNSLQGLFIFVFHCALKENVQ----KQWRR 269
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
187-460 2.29e-07

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: 52.45  E-value: 2.29e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRL-HCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATldeaerlteeelraia 265
Cdd:cd15443    4 LTYISIVGCSISAAASLLTILLHFFSRKQpKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQST---------------- 67
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 266 qappppataaagyAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTVFGWGLPAVFVAVWVSVRA 344
Cdd:cd15443   68 -------------WLCRAAAALLHYSLLCCLTWMAIEGFHLYLLLVKVYNIYiRRYVLKLCVLGWGLPALIVLLVLIFKR 134
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 345 TLANTGCWDLSSGNKK----WIIQVPILASIVLNF---ILFINIVrVLATKLR-------ETNAGRCDTRQQYRKLLKST 410
Cdd:cd15443  135 EAYGPHTIPTGTGYQNasmcWITSSKVHYVLVLGYaglTSLFNLV-VLAWVVRmlrrlrsRKQELGERARRDWVTVLGLT 213
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 296080761 411 LVLMPLFGVHYIVFmatpytevsGTLWQVQMHYEMLFNSFQGFFVAIIYC 460
Cdd:cd15443  214 CLLGTTWALAFFSF---------GVFLIPQLFLFTIINSLYGFFICLWYC 254
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
281-471 1.78e-06

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: 49.56  E-value: 1.78e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 281 CRVAVTFFLYFLATNYYWILVEGlYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLA---NTGCWDLSSG 357
Cdd:cd15251   68 CTMTAAFLHFFFLSSFCWVLTEA-WQSYMAVTGRMRTRLIRKRFLCLGWGLPALVVAVSVGFTRTKGygtSSYCWLSLEG 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 358 NKKWIIQVPILASIVLNFILFINIVRVLATKLRET-NAGRCdtrqqyrklLKSTLVLMPLFGVHYIVFMATpYTEVSGTL 436
Cdd:cd15251  147 GLLYAFVGPAAAVVLVNMVIGILVFNKLVSRDGISdNAMAS---------LWSSCVVLPLLALTWMSAVLA-MTDRRSVL 216
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 296080761 437 WQVQMhyeMLFNSFQGFFVAIIYCFCNGEVQAEIK 471
Cdd:cd15251  217 FQILF---AVFDSLQGFVIVMVHCILRREVQDAVK 248
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
280-455 7.05e-06

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


Pssm-ID: 320660 [Multi-domain]  Cd Length: 267  Bit Score: 47.91  E-value: 7.05e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 280 GCrVAVTFFLYFLATN-YYWILVEGLYLHSLIFMAFFSEKKYLWGFTVF--GWGLPAVFVAVWVSV----RATLANTGCW 352
Cdd:cd15994   75 LC-VAATFFLHFFYLSlFFWMLTKALLILYGILLVFFKITKSVFIATAFsiGYGCPLVIAVLTVAItepkKGYLRPEACW 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 353 dLSSGNKKWIIQ--VPILASIVLNFIlfinIVRVLATKLRETNAGRcDTRQQYRKLL---KSTLVLMPLFGVHYIVFMAT 427
Cdd:cd15994  154 -LNWDETKALLAfiIPALSIVVVNLI----VVGVVVVKTQRSSIGE-SCKQDVSNIIrisKNVAILTPLLGLTWGFGLAT 227
                        170       180
                 ....*....|....*....|....*...
gi 296080761 428 PyteVSGTLWQVQMHYEMLfNSFQGFFV 455
Cdd:cd15994  228 I---IDSRSLPFHIIFALL-NAFQGFFI 251
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
281-471 7.47e-06

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


Pssm-ID: 320656  Cd Length: 267  Bit Score: 48.06  E-value: 7.47e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 281 CRVAVTFFLYFLATNYYWILVEGlYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVwvSVRATLAN-----TGCWDLS 355
Cdd:cd15990   71 CTLVAAFLHFFFLSSFCWVLTEA-WQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAI--SVGFTKAKgygtvNYCWLSL 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 356 SGNKKWIIQVPILASIVLNFILFINIVRVLATKLRETNAgrcDTRQQYRKLLKSTLVLMPLFGVHYIVFMATpYTEVSGT 435
Cdd:cd15990  148 EGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKDGITDK---KLKERAGASLWSSCVVLPLLALTWMSAVLA-ITDRRSA 223
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 296080761 436 LWQVQMhyeMLFNSFQGFFVAIIYCFCNGEVQAEIK 471
Cdd:cd15990  224 LFQILF---AVFDSLEGFVIVMVHCILRREVQDAVK 256
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
187-480 9.93e-06

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: 47.53  E-value: 9.93e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLflsfmlrAVSIFVKDAVLYSGATLDEAERLteeelraiaq 266
Cdd:cd15993    4 LAIVTYSSVSASLAALVLTFSVLTCLRGLKSNTRGIHSNI-------AAALFLSELLFLLGINRTENQFL---------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 267 appppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRAT- 345
Cdd:cd15993   67 --------------CTVVAILLHYFFLSTFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLDPEg 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 346 LANTG-CWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLatklretnagrCDTRQQYRK------LLKSTLVLMPLFG 418
Cdd:cd15993  133 YGNPDfCWISIHDKLVWSFAGPIVVVIVMNGVMFLLVARMS-----------CSPGQKETKktsvlmTLRSSFLLLLLIS 201
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296080761 419 VHYIVFMATPYTEVsgtlwqVQMHY-EMLFNSFQGFFVAIIYCFCNGEVQAEikkswsrWTLA 480
Cdd:cd15993  202 ATWLFGLLAVNNSV------LAFHYlHAILCCLQGLAVLLLFCVLNEEVQEA-------WKLA 251
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
185-475 5.59e-05

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


Pssm-ID: 320382 [Multi-domain]  Cd Length: 275  Bit Score: 45.18  E-value: 5.59e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 185 DRLGMIYTVGYSVSLASLTVAVLILAYFRRlHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEELrai 264
Cdd:cd15254    2 DELDYITYIGLSISILSLAICIVIESLVWK-SVTKNRTSYMRHVCILNIAVSLLIADIWFIVVAAIQDQNYAVNGNV--- 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 265 aqappppataaagyagCRVAVTFFLYFLATNYYWILVEGLYL-HSLIFMAFFSEKKYLWGFTV-FGWGLPAVFVAVWVSV 342
Cdd:cd15254   78 ----------------CVAATFFIHFFYLCVFFWMLALGLMLfYRLVFILHDTSKTIQKAVAFcLGYGCPLIISVITIAV 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 343 ----RATLANTGCWdLSSGNKKWIIQVPILASIVLNFILFINIVrVLATKLRETnAGRCDTRQQYRKLL---KSTLVLMP 415
Cdd:cd15254  142 tlprDSYTRKKVCW-LNWEDSKALLAFVIPALIIVAVNSIITVV-VIVKILRPS-IGEKPSKQERSSLFqiiKSIGVLTP 218
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 416 LFGVHYIVFMATPyteVSGTLWQVQMHYeMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWS 475
Cdd:cd15254  219 LLGLTWGFGLATV---IKGSSIVFHILF-TLLNAFQGLFILVFGTLWDKKVQEALLNKYS 274
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
187-459 1.22e-04

orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR56 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR64, GPR97, GPR112, GPR114, and GPR126. GPR56 is involved in the regulation of oligodendrocyte development and myelination in the central nervous system via coupling to G(12/13) proteins, which leads to the activation of RhoA GTPase. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320661  Cd Length: 269  Bit Score: 44.05  E-value: 1.22e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 187 LGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRN-YIHMHLFLSFMLRAVSIFVKDAVLYSGATLdeaerlteeelraia 265
Cdd:cd15995    4 LTILTYVGCIISALASVFTIAFYLCSRRKPRDYTiYVHMNLLLAIFLLDTSFLISEPLALTGSEA--------------- 68
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 266 qappppataaagyaGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTVFGWGLPAVFV-------- 336
Cdd:cd15995   69 --------------ACRAGGMFLHFSLLACLTWMGIEGYNLYRLVVEVFNTYvPHFLLKLCAVGWGLPIFLVtliflvdq 134
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 337 --------AVWVSVRATLANTGCWdlssgnkkwiIQVPILASIV----LNFILFINIVrVLATKLRETNAGRCDTRQqyr 404
Cdd:cd15995  135 dnygpiilAVHRSPEKVTYATICW----------ITDSLISNITnlglFSLVFLFNMA-MLATMVVEILRLRPRTHK--- 200
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 296080761 405 klLKSTLVLMPLFGVHYIVFMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIY 459
Cdd:cd15995  201 --WSHVLTLLGLSLVLGIPWALAFFSFASGTFQLVIVYLFTIINSLQGFLIFLWY 253
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
281-467 5.49e-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: 5.49e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 281 CRVAVTFFLYFLATNYYWILVEGlYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLA---NTGCWDLSSG 357
Cdd:cd15989   70 CTMTTAFLHFFFLASFCWVLTEA-WQSYMAVTGKIRTRLIRKRFLCLGWGLPALVVAISMGFTKAKGygtPHYCWLSLEG 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 358 NKKWIIQVPILASIVLNFILFINIVR-------VLATKLRE-----------------------TNAGRCDTRQQYRKLL 407
Cdd:cd15989  149 GLLYAFVGPAAAVVLVNMVIGILVFNklvsrdgILDKKLKHragqmsephsgltlkcakcgvvsTTALSATTASNAMASL 228
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 296080761 408 KSTLVLMPLFGVHYIVFMATpYTEVSGTLWQVQMhyeMLFNSFQGFFVAIIYCFCNGEVQ 467
Cdd:cd15989  229 WSSCVVLPLLALTWMSAVLA-MTDKRSILFQILF---AVFDSLQGFVIVMVHCILRREVQ 284
 
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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