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Conserved domains on  [gi|1937369810|ref|NP_073205|]
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corticotropin-releasing factor receptor 2 precursor [Rattus norvegicus]

Protein Classification

hormone receptor( domain architecture ID 12183103)

hormone receptor is a G-protein coupled receptor (GPCR) for hormones and/or hormone-related peptides, similar to corticotropin-releasing factor receptor, parathyroid hormone/parathyroid hormone-related peptide receptor, and vasoactive intestinal polypeptide receptor; contains the large N-terminal extracellular domain that plays a critical role in peptide hormone recognition

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 ...
113-376 3.05e-174

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 cd15446:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 264  Bit Score: 486.77  E-value: 3.05e-174
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVHEGNEVWCRCVTTIFN 192
Cdd:cd15446     1 YKIALIINYLGHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFLLQMIDHNIHESNEVWCRCITTIYN 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVDYIYQGPI 272
Cdd:cd15446    81 YFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYENEQCWFGKEPGKYIDYIYQGPV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 273 ILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFIYFNSFLQSFQG 352
Cdd:cd15446   161 ILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDISQIVFIYFNSFLQSFQG 240
                         250       260
                  ....*....|....*....|....
gi 1937369810 353 FFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15446   241 FFVSVFYCFLNGEVRSAARKRWHR 264
HormR smart00008
Domain present in hormone receptors;
36-107 4.02e-21

Domain present in hormone receptors;


:

Pssm-ID: 214468  Cd Length: 70  Bit Score: 86.41  E-value: 4.02e-21
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937369810   36 PYSYCNTTLDQIgTCWPQSAPGALVERPCPEYFNGIKYNTTrnAYRECLENGTWASR-VNYSHCEPILDDKQR 107
Cdd:smart00008   1 TDLGCPATWDGI-ICWPQTPAGQLVEVPCPKYFSGFSYKTG--ASRNCTENGGWSPPfPNYSNCTSNDYEELK 70
 
Name Accession Description Interval E-value
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
113-376 3.05e-174

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: 486.77  E-value: 3.05e-174
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVHEGNEVWCRCVTTIFN 192
Cdd:cd15446     1 YKIALIINYLGHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFLLQMIDHNIHESNEVWCRCITTIYN 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVDYIYQGPI 272
Cdd:cd15446    81 YFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYENEQCWFGKEPGKYIDYIYQGPV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 273 ILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFIYFNSFLQSFQG 352
Cdd:cd15446   161 ILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDISQIVFIYFNSFLQSFQG 240
                         250       260
                  ....*....|....*....|....
gi 1937369810 353 FFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15446   241 FFVSVFYCFLNGEVRSAARKRWHR 264
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
118-355 1.62e-80

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: 247.96  E-value: 1.62e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDH---EVHEGNEVWCRCVTTIFNYF 194
Cdd:pfam00002   6 VIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFnkqDLDHCSWVGCKVVAVFLHYF 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 195 VVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVG--KLYYENEQCWFGKEPGDLvdYIYQGPI 272
Cdd:pfam00002  86 FLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCWLSNENGLW--WIIRGPI 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 273 ILVLLINFVFLFNIVRILMTKLRASTTSETI--QYRKAVKATLVLLPLLGITYM--LFFVNPgeDDLSQIVFIYFNSFLQ 348
Cdd:pfam00002 164 LLIILVNFIIFINIVRILVQKLRETNMGKSDlkQYRRLAKSTLLLLPLLGITWVfgLFAFNP--ENTLRVVFLYLFLILN 241

                  ....*..
gi 1937369810 349 SFQGFFV 355
Cdd:pfam00002 242 SFQGFFV 248
HormR smart00008
Domain present in hormone receptors;
36-107 4.02e-21

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 86.41  E-value: 4.02e-21
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937369810   36 PYSYCNTTLDQIgTCWPQSAPGALVERPCPEYFNGIKYNTTrnAYRECLENGTWASR-VNYSHCEPILDDKQR 107
Cdd:smart00008   1 TDLGCPATWDGI-ICWPQTPAGQLVEVPCPKYFSGFSYKTG--ASRNCTENGGWSPPfPNYSNCTSNDYEELK 70
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
37-101 6.38e-19

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: 80.11  E-value: 6.38e-19
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937369810  37 YSYCNTTLDQIgTCWPQSAPGALVERPCPEYFNGIKYNttRNAYRECLENGTWASR--VNYSHCEPI 101
Cdd:pfam02793   1 GLGCPRTWDGI-LCWPRTPAGETVEVPCPDYFSGFDPR--GNASRNCTEDGTWSEHppSNYSNCTSN 64
 
Name Accession Description Interval E-value
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
113-376 3.05e-174

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: 486.77  E-value: 3.05e-174
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVHEGNEVWCRCVTTIFN 192
Cdd:cd15446     1 YKIALIINYLGHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFLLQMIDHNIHESNEVWCRCITTIYN 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVDYIYQGPI 272
Cdd:cd15446    81 YFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYENEQCWFGKEPGKYIDYIYQGPV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 273 ILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFIYFNSFLQSFQG 352
Cdd:cd15446   161 ILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDISQIVFIYFNSFLQSFQG 240
                         250       260
                  ....*....|....*....|....
gi 1937369810 353 FFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15446   241 FFVSVFYCFLNGEVRSAARKRWHR 264
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
113-376 1.32e-164

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: 462.66  E-value: 1.32e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVHEGNEVW-CRCVTTIF 191
Cdd:cd15264     1 YKVALIIYYLGFSISLVALAVALIIFLYFRSLRCLRNNIHCNLIVTFILRNVTWFIMQNTLTEIHHQSNQWvCRLIVTVY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 192 NYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVDYIYQGP 271
Cdd:cd15264    81 NYFQVTNFFWMFVEGLYLHTMIVWAYSADKIRFWYYIVIGWCIPCPFVLAWAIVKLLYENEHCWLPKSENSYYDYIYQGP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 272 IILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFIYFNSFLQSFQ 351
Cdd:cd15264   161 ILLVLLINFIFLFNIVWVLITKLRASNTLETIQYRKAVKATLVLLPLLGITYMLFFINPGDDKTSRLVFIYFNTFLQSFQ 240
                         250       260
                  ....*....|....*....|....*
gi 1937369810 352 GFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15264   241 GLFVAVFYCFLNGEVRSAIRKKFSR 265
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
113-376 1.48e-158

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: 447.07  E-value: 1.48e-158
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQL-IDHEVHEGNEVWCRCVTTIF 191
Cdd:cd15445     1 YHIAVIINYLGHCISLVALLVAFVLFLRLRSIRCLRNIIHWNLITAFILRNATWFVVQLtMSPEVHQSNVVWCRLVTAAY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 192 NYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVDYIYQGP 271
Cdd:cd15445    81 NYFHVTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFICIGWCIPFPIIVAWAIGKLYYDNEKCWFGKRAGVYTDYIYQGP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 272 IILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFIYFNSFLQSFQ 351
Cdd:cd15445   161 MILVLLINFIFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDEISRIVFIYFNSFLESFQ 240
                         250       260
                  ....*....|....*....|....*
gi 1937369810 352 GFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15445   241 GFFVSVFYCFLNSEVRSAVRKRWHR 265
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
113-376 1.42e-107

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: 318.01  E-value: 1.42e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLI----------DHEVHEGNEV 182
Cdd:cd15041     1 LLVVYYIYLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFLSFILRAVFWIIWDLLvvydrltssgVETVLMQNPV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 183 WCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWfGKEPGD 262
Cdd:cd15041    81 GCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSSLKLYYAIGWGLPLVIVVIWAIVRALLSNESCW-ISYNNG 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 263 LVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFIY 342
Cdd:cd15041   160 HYEWILYGPNLLALLVNLFFLINILRILLTKLRSHPNAEPSNYRKAVKATLILIPLFGIQYLLTIYRPPDGSEGELVYEY 239
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1937369810 343 FNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15041   240 FNAILNSSQGFFVAVIYCFLNGEVQSELKRKWSR 273
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
118-376 2.16e-83

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: 256.14  E-value: 2.16e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWfLLQLIDHEVHEGNEVWCRCVTTIFNYFVVT 197
Cdd:cd15263     6 TIYFIGYSLSLVALSLALWIFLYFKDLRCLRNTIHTNLMFTYILADLTW-ILTLTLQVSIGEDQKSCIILVVLLHYFHLT 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLY---YENEQCWFGKEPG-------DLVDYI 267
Cdd:cd15263    85 NFFWMFVEGLYLYMLVVETFSGENIKLRVYAFIGWGIPAVVIVIWAIVKALaptAPNTALDPNGLLKhcpwmaeHIVDWI 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 268 YQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPgEDDLSQIVFIYFNSFL 347
Cdd:cd15263   165 FQGPAILVLAVNLVFLVRIMWVLITKLRSANTVETQQYRKAAKALLVLIPLLGITYILVIAGP-TEGIAANIFEYVRAVL 243
                         250       260
                  ....*....|....*....|....*....
gi 1937369810 348 QSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15263   244 LSTQGFTVALFYCFLNTEVRNTLRHHFER 272
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
118-355 1.62e-80

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: 247.96  E-value: 1.62e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDH---EVHEGNEVWCRCVTTIFNYF 194
Cdd:pfam00002   6 VIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFnkqDLDHCSWVGCKVVAVFLHYF 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 195 VVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVG--KLYYENEQCWFGKEPGDLvdYIYQGPI 272
Cdd:pfam00002  86 FLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCWLSNENGLW--WIIRGPI 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 273 ILVLLINFVFLFNIVRILMTKLRASTTSETI--QYRKAVKATLVLLPLLGITYM--LFFVNPgeDDLSQIVFIYFNSFLQ 348
Cdd:pfam00002 164 LLIILVNFIIFINIVRILVQKLRETNMGKSDlkQYRRLAKSTLLLLPLLGITWVfgLFAFNP--ENTLRVVFLYLFLILN 241

                  ....*..
gi 1937369810 349 SFQGFFV 355
Cdd:pfam00002 242 SFQGFFV 248
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
118-376 7.58e-72

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: 226.39  E-value: 7.58e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYL---GHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFL---LQLIDHEVHEGNEVWCRCVTTIF 191
Cdd:cd15260     3 FVNYVyigGYSVSLIALIISLAIFFSFRSLRCTRITIHMNLFISFALNNLLWIVwykLVVDNPEVLLENPIWCQALHVLL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 192 NYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYY--ENEQCWFGKepgDLVDYIYQ 269
Cdd:cd15260    83 QYFMVCNYFWMFCEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLpdDTERCWMEE---SSYQWILI 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 270 GPIILVLLINFVFLFNIVRILMTKLRA-STTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFIYFNSFLQ 348
Cdd:cd15260   160 VPVVLSLLINLIFLINIVRVLLTKLRAtSPNPAPAGLRKAVRATLILIPLLGLQFLLIPFRPEPGAPLETIYQYVSALLT 239
                         250       260
                  ....*....|....*....|....*...
gi 1937369810 349 SFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15260   240 SLQGLCVAVLFCFCNGEVIAAIKRKWRR 267
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
114-376 3.44e-70

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: 222.65  E-value: 3.44e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 114 RIALIINyLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFL-----LQLIDHEV------------ 176
Cdd:cd15272     3 SIRLMYN-IGYGLSLVSLLIAVIIMLYFKKLHCPRNTIHINLFVSFILRAVLSFIkenllVQGVGFPGdvyydsngvief 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 177 -HEGNEVWCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCW 255
Cdd:cd15272    82 kDEGSHWECKLFFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLLFVLPWVFVRATLEDTLCW 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 256 fGKEPGDLVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSET--IQYRKAVKATLVLLPLLGITYMLFFVNPG-- 331
Cdd:cd15272   162 -NTNTNKGYFWIIRGPIVISIAINFLFFINIVRVLFTKLKASNTQESrpFRYRKLAKSTLVLIPLFGVHYMVFVVLPDsm 240
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937369810 332 EDDLSQIVFIYFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15272   241 SSDEAELVWLYFEMFFNSFQGFIVALLFCFLNGEVQSEIKKKWQR 285
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
118-376 1.34e-59

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: 195.67  E-value: 1.34e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVHEGNE---------------- 181
Cdd:cd15265     6 LIYTVGYSISLVSLTVAVFILGYFRRLHCTRNYIHMHLFVSFMLRAVSIFVKDAVLYSGSGLDElerpsmedlksiveap 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 182 -------VWCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQC 254
Cdd:cd15265    86 pvdksqyVGCKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVFVIPWASVRATLADTRC 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 255 WfgkepgDLVD----YIYQGPIILVLLINFVFLFNIVRILMTKLR---ASTTSETIQYRKAVKATLVLLPLLGITYMLFF 327
Cdd:cd15265   166 W------DLSAgnykWIYQVPILAAIVVNFILFLNIVRVLATKLRetnAGRCDTRQQYRKLAKSTLVLIPLFGVHYIVFM 239
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937369810 328 VNPgEDDLSQI--VFIYFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15265   240 GMP-YTEVGLLwqIRMHYELFFNSFQGFFVAIIYCFCNGEVQAEIKKRWER 289
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
118-376 3.18e-59

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: 193.80  E-value: 3.18e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNIT-----WFLLQLIDHEVHEGNEVWCRCVTTIFN 192
Cdd:cd15930     6 IIYTVGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAvfikdAVLFSSEDVDHCFVSTVGCKASMVFFQ 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWfgkepgDLVD-----YI 267
Cdd:cd15930    86 YCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVWIVARLYFEDTGCW------DINDespywWI 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 268 YQGPIILVLLINFVFLFNIVRILMTKLRASTTS--ETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDLSQIVFIYFNS 345
Cdd:cd15930   160 IKGPILISILVNFVLFINIIRILLQKLRSPDIGgnESSQYKRLARSTLLLIPLFGIHYIVFAFFP--ENISLGIRLYFEL 237
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1937369810 346 FLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15930   238 CLGSFQGFVVAVLYCFLNGEVQAEIKRKWRS 268
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
114-376 1.43e-58

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: 192.59  E-value: 1.43e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 114 RIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFL-----------LQLIDHEVHEGNEV 182
Cdd:cd15273     2 PIIKGISQIGYIVSLITLIIAFAIFLSFKKLHCARNKLHMHLFASFILRAFMTLLkdslfidglglLADIVERNGGGNEV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 183 W--------CRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQC 254
Cdd:cd15273    82 IanigsnwvCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVPWIVARILFENSLC 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 255 WFGKEPGDLVdYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDD 334
Cdd:cd15273   162 WTTNSNLLNF-LIIRIPIMISVLINFILFLNIVRVLLVKLRSSVNEDSRRYKKWAKSTLVLVPLFGVHYTIFLILSYLDD 240
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937369810 335 LSQ---IVFIYFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15273   241 TNEaveLIWLFCDQLFASFQGFFVALLYCFLNGEVRAEIQRKWRR 285
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
113-370 1.56e-58

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: 191.66  E-value: 1.56e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIdheVHEGNEVWCRCVTTIFN 192
Cdd:cd13952     1 DLALSIITYIGCSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLL---TSSDRPVLCKALAILLH 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRK-WLFLFIGWCIPCPIIVAWAV-------GKLYYENEQCWFGkePGDLV 264
Cdd:cd13952    78 YFLLASFFWMLVEAFDLYRTFVKVFGSSERRRfLKYSLYGWGLPLLIVIITAIvdfslygPSPGYGGEYCWLS--NGNAL 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 265 DYIYQGPIILVLLINFVFLFNIVRILMTKLRASTT-SETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDdlSQIVFIYF 343
Cdd:cd13952   156 LWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKqSERKSDRKQLRAYLKLFPLMGLTWIFGILAPFVG--GSLVFWYL 233
                         250       260
                  ....*....|....*....|....*..
gi 1937369810 344 NSFLQSFQGFFVSVFYCFFNGEVRSAL 370
Cdd:cd13952   234 FDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
123-376 9.42e-58

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: 189.95  E-value: 9.42e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 123 GHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWF-----LLQLIDHEVHEGNEVWCRCVTTIFNYFVVT 197
Cdd:cd15275    11 GYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFikdavLFSSEDDNHCDIYTVGCKVAMVFSNYCIMA 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVdYIYQGPIILVLL 277
Cdd:cd15275    91 NYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFIISWAIARYLHENEGCWDTRRNAWIW-WIIRGPVILSIF 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 278 INFVFLFNIVRILMTKLRASTT--SETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDLSQIVFIYFNSF---LQSFQG 352
Cdd:cd15275   170 VNFILFLNILRILMRKLRAPDMrgNEFSQYKRLAKSTLLLIPLFGLHYILFAFFP--EDVSSGTMEIWLFFelaLGSFQG 247
                         250       260
                  ....*....|....*....|....
gi 1937369810 353 FFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15275   248 FVVAVLYCFLNGEVQLEIQRKWRR 271
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
113-380 2.74e-57

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: 189.22  E-value: 2.74e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIinylGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRN---ITWFLLQLIDHEVHEGNEVWCRCVTT 189
Cdd:cd15274     5 YYLAIV----GHSLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSiiiIIHLVAVVPNGELVARNPVSCKILHF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 190 IFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLvdYIYQ 269
Cdd:cd15274    81 IHQYMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAITRAVYYNDNCWLSSETHLL--YIIH 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 270 GPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPgEDDLSQIVFIYFNSFLQS 349
Cdd:cd15274   159 GPIMAALVVNFFFLLNIVRVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQFVLFPWRP-SGKILGKIYDYVMHSLIH 237
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1937369810 350 FQGFFVSVFYCFFNGEVRSALRKRWHRWQDH 380
Cdd:cd15274   238 FQGFFVATIFCFCNGEVQATLKRQWNQYKIQ 268
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
114-376 3.33e-57

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: 189.12  E-value: 3.33e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 114 RIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWfLLQLIDHEVHEGNE------------ 181
Cdd:cd15261     2 RGTRTLEIVGLCLSLVSLIISLFIFSYFRTLRNHRTRIHKNLFLAILLQVIIR-LVLYIDQAITRSRGshtnaattegrt 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 182 -----VWCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWA-VGKLYYENEQCW 255
Cdd:cd15261    81 instpILCEGFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAiVTLIKMKVNRCW 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 256 FGK--EPgdlVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFV--NPG 331
Cdd:cd15261   161 FGYylTP---YYWILEGPRLAVILINLFFLLNIIRVLVSKLRESHSREIEQVRKAVKAAIVLLPLLGITNILQMIppPLT 237
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937369810 332 EDDLSQIVFIYFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15261   238 SVIVGFAVWSYSTHFLTSFQGFFVALIYCFLNGEVKNVLKKFWRR 282
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
118-376 1.44e-56

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: 187.26  E-value: 1.44e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVH---------------EGNEV 182
Cdd:cd15266     6 LIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDIVLYSTYskrpddetgwisylsEESST 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 183 WCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHlRKWL-FLFIGWCIPCPIIVAWAVGKLYYENEQCWfGKEPG 261
Cdd:cd15266    86 SCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSER-RLLKkYMLIGWGTPVLFVVPWGVAKILLENTGCW-GRNEN 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 262 DLVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDLSQIVFI 341
Cdd:cd15266   164 MGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYKYRLARSTLVLIPLLGIHEVVFSFIT--DEQVEGFSR 241
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937369810 342 YFNSFLQ----SFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15266   242 HIRLFIQltlsSFQGFLVAVLYCFANGEVKAELKKRWQL 280
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
123-374 1.26e-54

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: 181.85  E-value: 1.26e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 123 GHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLI---DHEVHEG--NEVWCRCVTTIFNYFVVT 197
Cdd:cd15271    11 GYGTSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALAVFIKDAVlfaDESVDHCtmSTVACKAAVTFFQFCVLA 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGdlVDYIYQGPIILVLL 277
Cdd:cd15271    91 NFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVWVLTRLQYDNRGCWDDLESR--IWWIIKTPILLSVF 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 278 INFVFLFNIVRILMTKLRA--STTSETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDLSQIVFIYFNSFLQSFQGFFV 355
Cdd:cd15271   169 VNFLIFINVIRILVQKLKSpdVGGNDTSHYMRLAKSTLLLIPLFGVHYVVFAFFP--EHVGVEARLYFELVLGSFQGFIV 246
                         250
                  ....*....|....*....
gi 1937369810 356 SVFYCFFNGEVRSALRKRW 374
Cdd:cd15271   247 ALLYCFLNGEVQAEIKKRL 265
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
122-376 1.86e-54

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: 181.59  E-value: 1.86e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 122 LGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVHEGNE-----VWCRCVTTIFNYFVV 196
Cdd:cd15269    10 IGHSLSLISLTAAMIILCLFRKLHCTRNYIHMHLFMSFILRAIAVFIKDAVLFESGEEDHcsvasVGCKAAMVFFQYCIM 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 197 TNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWfGKEPGDLVDYIYQGPIILVL 276
Cdd:cd15269    90 ANFFWLLVEGLYLHTLLAVSFFSERKYFWWYILIGWGAPSVFITAWSVARIYFEDVGCW-DTIIESLLWWIIKTPILVSI 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 277 LINFVFLFNIVRILMTKLRASTT--SETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDLSQIVFIYFNSFLQSFQGFF 354
Cdd:cd15269   169 LVNFILFICIIRILVQKLHSPDIgrNESSQYSRLAKSTLLLIPLFGIHYIMFAFFP--DNFKAEVKLVFELILGSFQGFV 246
                         250       260
                  ....*....|....*....|..
gi 1937369810 355 VSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15269   247 VAVLYCFLNGEVQAELKRKWRR 268
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
118-376 6.64e-53

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: 177.63  E-value: 6.64e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWF----LLQLIdHEVHEGNEVW---------- 183
Cdd:cd15929     6 VMYTVGYSLSLAALVLALAILLGLRKLHCTRNYIHANLFASFILRALSVLvkdaLLPRR-YSQKGDQDLWstllsnqasl 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 184 -CRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWfgkEPGD 262
Cdd:cd15929    85 gCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLLLGWGAPVLFVVPWGIVKYLYENTGCW---TRND 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 263 LVDY--IYQGPIILVLLINFVFLFNIVRILMTKLRASTTSET-IQYRKAvKATLVLLPLLGITYMLFFVNPGEDDLSQIV 339
Cdd:cd15929   162 NMAYwwIIRLPILLAILINFFIFVRILKILVSKLRANQMCKTdYKFRLA-KSTLTLIPLLGVHEVVFAFVTDEQARGTLR 240
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937369810 340 FI--YFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15929   241 FIklFFELFLSSFQGLLVAVLYCFANKEVQSELRKKWHR 279
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
113-376 2.12e-51

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: 173.44  E-value: 2.12e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWF-----LLQLIDHEVHEGNEVWCRCV 187
Cdd:cd15270     1 FSTVKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFikdaaLFQEDDTDHCSMSTVLCKVS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 188 TTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVdYI 267
Cdd:cd15270    81 VVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCKLYFEDTECWDINNDSPYW-WI 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 268 YQGPIILVLLINFVFLFNIVRILMTKL--RASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDLSQIVFIYFNS 345
Cdd:cd15270   160 IKGPIVISVGVNFLLFLNIIRILLKKLdpRQINFNNSAQYRRLSKSTLLLIPLFGTHYIIFNFLP--DYAGLGIRLYLEL 237
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1937369810 346 FLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15270   238 CLGSFQGFIVAVLYCFLNQEVQTEISRKWYG 268
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
118-376 5.24e-51

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: 173.21  E-value: 5.24e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFL-------------LQLIDHE--------- 175
Cdd:cd15984     6 LIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVSIFVkdavlysgsaleeMERITEEdlksiteap 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 176 -VHEGNEVWCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQC 254
Cdd:cd15984    86 pADKAQFVGCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVRATLADTGC 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 255 WfGKEPGDLvDYIYQGPIILVLLINFVFLFNIVRILMTKLR---ASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPg 331
Cdd:cd15984   166 W-DLSAGNL-KWIIQVPILAAIVVNFILFINIVRVLATKLRetnAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVFMAMP- 242
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1937369810 332 EDDLSQIVF---IYFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15984   243 YTEVSGILWqvqMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSR 290
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
122-376 5.62e-49

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: 167.79  E-value: 5.62e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 122 LGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVHEGNE------------------VW 183
Cdd:cd15983    10 IGYSISLAALLVAVCILCYFKRLHCTRNYIHIHLFASFICRAGSIFVKDAVLYSGTNEGEaldekiefglspgtrlqwVG 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 184 CRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWfGKEPGDL 263
Cdd:cd15983    90 CKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVRVSLADTQCW-DLSAGNL 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 264 vDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSET---IQYRKAVKATLVLLPLLGITYMLFFVNPgEDDLSQIVF 340
Cdd:cd15983   169 -KWIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKLdprQQYRKLLKSTLVLMPLFGVHYVLFMAMP-YTDVTGLLW 246
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937369810 341 ---IYFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15983   247 qiqMHYEMLFNSSQGFFVAFIYCFCNGEVQAEIKKAWLR 285
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
113-374 1.09e-47

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: 163.82  E-value: 1.09e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLI-------DHEVHEGNEVWCR 185
Cdd:cd15986     1 YIVVKTIYTLGHSVSLIALTTGSTILCLFRKLHCTRNYIHLNLFFSFILRAISVLVKDDIlysssntEHCTVPPSLIGCK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 186 CVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYStEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEpGDLVD 265
Cdd:cd15986    81 VSLVILQYCIMANFYWLLVEGLYLHTLLVVIFS-ENRHFIVYLLIGWGIPTVFIIAWIVARIYLEDTGCWDTND-HSVPW 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 266 YIYQGPIILVLLINFVFLFNIVRILMTKLRASTT--SETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDLSQIVFIYF 343
Cdd:cd15986   159 WVIRIPIIISIILNFILFISIIRILLQKLRSPDVggNDQSQYKRLAKSTLLLIPLFGVHYIVFVYFP--DSSSSNYQIFF 236
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1937369810 344 NSFLQSFQGFFVSVFYCFFNGEVRSALRKRW 374
Cdd:cd15986   237 ELCLGSFQGLVVAILYCFLNSEVQGELKRKW 267
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
122-374 1.77e-47

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: 163.22  E-value: 1.77e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 122 LGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHEVHEGNE-----VWCRCVTTIFNYFVV 196
Cdd:cd15987    10 VGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQDSDHcfvstVECKAVMVFFHYCVM 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 197 TNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVdYIYQGPIILVL 276
Cdd:cd15987    90 SNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLRLHFDDTGCWDMNDNTALW-WVIKGPVVGSI 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 277 LINFVFLFNIVRILMTKLRASTT--SETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDLSQIVFIYFNSFLQSFQGFF 354
Cdd:cd15987   169 MINFVLFIGIIIILVQKLQSPDIggNESSIYLRLARSTLLLIPLFGIHYTVFAFSP--ENVSKRERLVFELGLGSFQGFV 246
                         250       260
                  ....*....|....*....|
gi 1937369810 355 VSVFYCFFNGEVRSALRKRW 374
Cdd:cd15987   247 VAVLYCFLNGEVQSEIKRKW 266
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
118-376 4.52e-47

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: 162.80  E-value: 4.52e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHE---------------------- 175
Cdd:cd15982     6 IMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAASIFVKDKVVHThigvkeldavlmndfqnavdap 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 176 -VHEGNEVWCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQC 254
Cdd:cd15982    86 pVDKSQYVGCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAAWAVVRATLADARC 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 255 WfGKEPGDlVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTT---SETIQYRKAVKATLVLLPLLGITYMLFFVNPG 331
Cdd:cd15982   166 W-ELSAGD-IKWIYQAPILAAIGLNFILFLNTVRVLATKIWETNAvgyDTRKQYRKLAKSTLVLVLVFGVHYIVFVCLPH 243
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1937369810 332 E-DDLSQIVFIYFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15982   244 TfTGLGWEIRMHCELFFNSFQGFFVSIIYCYCNGEVQTEIKKTWTR 289
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
118-376 4.88e-47

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: 162.68  E-value: 4.88e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLL---------QLIDHEVH-----EGNEVW 183
Cdd:cd15267     8 VMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASSVLVIdgllrtrysQKIEDDLSstwlsDEAVAG 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 184 CRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDL 263
Cdd:cd15267    88 CRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPALFVVPWVVVKCLYENVQCWTSNDNMGF 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 264 VdYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLS--QIVFI 341
Cdd:cd15267   168 W-WILRFPVFLAILINFFIFVRIIQILVSKLRARQMHYTDYKFRLAKSTLTLIPLLGIHEVVFAFVTDEHAQGtlRSAKL 246
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 1937369810 342 YFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15267   247 FFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHR 281
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
122-374 4.42e-44

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: 154.70  E-value: 4.42e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 122 LGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWF-------------LLQLIDHEVHEGNE--VWCRC 186
Cdd:cd15985    10 VGYTLSLLTLVSALLILTSIRKLHCTRNYIHANLFASFILRAVSVIvkdtllerrwgreIMRVADWGELLSHKaaIGCRM 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 187 VTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVdY 266
Cdd:cd15985    90 AQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVLFVVPWMLAKYLKENKECWALNENMAYW-W 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 267 IYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFI--YFN 344
Cdd:cd15985   169 IIRIPILLASLINLLIFMRILKVILSKLRANQKGYADYKLRLAKATLTLIPLFGIHEVVFIFATDEQTTGILRYIkvFFT 248
                         250       260       270
                  ....*....|....*....|....*....|
gi 1937369810 345 SFLQSFQGFFVSVFYCFFNGEVRSALRKRW 374
Cdd:cd15985   249 LFLNSFQGFLVAVLYCFANKEVKSELLKKW 278
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
126-376 5.59e-43

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: 151.44  E-value: 5.59e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 126 VSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLI----------DHEVHEGNEVWCRCVTTIFNYFV 195
Cdd:cd15262    14 VSVVTSLPAVFIFYSYKRLRITRVILHRNLLISIIIRNILVIISKVFvildaltssgDDTVMNQNAVVCRLLSIFERAAR 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 196 VTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLfIGWCIPCPIIVAWAVGKLYYENEQCWFgkEPGDLVDYIYQGPIILV 275
Cdd:cd15262    94 NAVFACMFVEGFYLHRLIVAVFAEKSSIRFLYV-IGAVLPLFPVIIWAIIRALHNDHSCWV--VDIEGVQWVLDTPRLFI 170
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 276 LLINFVFLFNIVRILMTKLRasTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDL-SQIVFIYFNSFLQSFQGFF 354
Cdd:cd15262   171 LLVNTVLLVDIIRVLVTKLR--NTEENSQTKSTTRATLFLVPLFGLHFVITAYRPSTDDCdWEDIYYYANYLIEGLQGFL 248
                         250       260
                  ....*....|....*....|..
gi 1937369810 355 VSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15262   249 VAILFCYINKEVHYLIKNTYRK 270
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
118-370 1.22e-39

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: 142.08  E-value: 1.22e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwfllqLIDHEVHEGNEVWCRCVTTIFNYFVVT 197
Cdd:cd15933     6 IISYIGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQIL-----LLAGEWAEGNKVACKVVAILLHFFFMA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTeHLRKWLFLFIGWCIPCpIIVAWAVG---KLYYENEQCWFGKEPGdlVDYIYQGPIIL 274
Cdd:cd15933    81 AFSWMLVEGLHLYLMIVKVFNY-KSKMRYYYFIGWGLPA-IIVAISLAilfDDYGSPNVCWLSLDDG--LIWAFVGPVIF 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 275 VLLINFVFLFNIVRILMTKLRAS---TTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEddlSQIVFIYFNSFLQSFQ 351
Cdd:cd15933   157 IITVNTVILILVVKITVSLSTNDakkSQGTLAQIKSTAKASVVLLPILGLTWLFGVLVVNS---QTIVFQYIFVILNSLQ 233
                         250
                  ....*....|....*....
gi 1937369810 352 GFFVSVFYCFFNGEVRSAL 370
Cdd:cd15933   234 GLMIFLFHCVLNSEVRSAF 252
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
118-376 1.00e-37

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: 137.78  E-value: 1.00e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFL-------LQLIDHEVHEGN-------EVW 183
Cdd:cd15268     6 IIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIkdaalkwMYSTAAQQHQWDgllsyqdSLS 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 184 CRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKLYYENEQCWFGKEPgdl 263
Cdd:cd15268    86 CRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFVIPWGIVKYLYEDEGCWTRNSN--- 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 264 VDY--IYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIVFI 341
Cdd:cd15268   163 MNYwlIIRLPILFAIGVNFLIFIRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFV 242
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1937369810 342 YFNSFLQ--SFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15268   243 KLFTELSftSFQGLMVAILYCFVNNEVQMEFRKSWER 279
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
118-376 3.49e-35

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: 130.46  E-value: 3.49e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQLIDHEvhegNEVWCRCVTTIFNYFVVT 197
Cdd:cd15440     6 FITYIGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLCLCLLIAEIV-FLLGIDQTE----NRTLCGVIAGLLHYFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCpIIVAWAVG---KLYYENEQCWFGKEPGdlVDYIYQGPIIL 274
Cdd:cd15440    81 AFSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLFGYGLPA-LIVAVSAGvdpTGYGTEDHCWLSTENG--FIWSFVGPVIV 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 275 VLLINFVFLFNIVRILMTKLRASTT----SETIQYRKAVKATLVLLPLLGITYM--LFFVNPGEddlsqIVFIYFNSFLQ 348
Cdd:cd15440   158 VLLANLVFLGMAIYVMCRHSSRSASkkdaSKLKNIRGWLKGSIVLVVLLGLTWTfgLLFINQES-----IVMAYIFTILN 232
                         250       260
                  ....*....|....*....|....*...
gi 1937369810 349 SFQGFFVSVFYCFFNGEVRSALRkRWHR 376
Cdd:cd15440   233 SLQGLFIFIFHCVLNEKVRKELR-RWLR 259
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
118-369 3.80e-34

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: 127.30  E-value: 3.80e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCL-RNVIHWNLITTFILRNITwFLLQLIDHEvhegNEVWCRCVTTIFNYFVV 196
Cdd:cd15040     6 IITYIGCGLSLLGLLLTIITYILFRKLRKRkPTKILLNLCLALLLANLL-FLFGINSTD----NPVLCTAVAALLHYFLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 197 TNFFWMFVEGCYLHTAIVMTYST--EHLRKWLFLfIGWCIPCPI--IVAWAVGKLYYENEQ-CWFgkEPGDLVDYIYQGP 271
Cdd:cd15040    81 ASFMWMLVEALLLYLRLVKVFGTypRHFILKYAL-IGWGLPLIIviITLAVDPDSYGNSSGyCWL--SNGNGLYYAFLGP 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 272 IILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLS-QIVFIYFNsflqSF 350
Cdd:cd15040   158 VLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQLRAAVSLFFLLGLTWIFGILAIFGARVVfQYLFAIFN----SL 233
                         250
                  ....*....|....*....
gi 1937369810 351 QGFFVSVFYCFFNGEVRSA 369
Cdd:cd15040   234 QGFFIFIFHCLRNKEVRKA 252
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
118-376 2.62e-28

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


Pssm-ID: 320557 [Multi-domain]  Cd Length: 254  Bit Score: 111.57  E-value: 2.62e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQLIDHEvhegNEVWCRCVTTIFNYFVVT 197
Cdd:cd15441     6 IVTYIGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELL-FLLGINQTE----NLFPCKLIAILLHYFYLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCpIIVAWAVG---KLYYENEQCWFGKEpgDLVDYIYQGPIIL 274
Cdd:cd15441    81 AFSWLLVESLHLYRMLTEPRDINHGHMRFYYLLGYGIPA-IIVGLSVGlrpDGYGNPDFCWLSVN--ETLIWSFAGPIAF 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 275 VLLINFVFLFNIVRILMTKLRASTTSETIQYRkaVKATLVLLPLLGITYM--LFFVNpGEDDLSQIVFIYFNsflqSFQG 352
Cdd:cd15441   158 VIVITLIIFILALRASCTLKRHVLEKASVRTD--LRSSFLLLPLLGATWVfgLLAVN-EDSELLHYLFAGLN----FLQG 230
                         250       260
                  ....*....|....*....|....
gi 1937369810 353 FFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15441   231 LFIFLFYCIFNKKVRRELKNALLR 254
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
119-373 2.78e-27

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


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 109.24  E-value: 2.78e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 119 INYLGHCVSVVALVAAFLLFLVLRSIRCLRNV---IHWNLITTFILRNItwflLQLIDHEVHEGNeVWCRCVTTIFNYFV 195
Cdd:cd15256     7 ITYVGCSLSIFCLAITLVTFAVLSSVSTIRNQryhIHANLSFAVLVAQI----LLLISFRFEPGT-LPCKIMAILLHFFF 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 196 VTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKL--YYENEQCWFGKEPGDLvdYIYQGPII 273
Cdd:cd15256    82 LSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGIGWGSPLLICIISLTSALdsYGESDNCWLSLENGAI--WAFVAPAL 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 274 LVLLINFVFLFNIVRILmTKLRASTTS---ETIQYRKAVKATLVLLPLLGITYMLFFVNPGEddlSQIVFIYFNSFLQSF 350
Cdd:cd15256   160 FVIVVNIGILIAVTRVI-SRISADNYKvhgDANAFKLTAKAVAVLLPILGSSWVFGVLAVNT---HALVFQYMFAIFNSL 235
                         250       260
                  ....*....|....*....|...
gi 1937369810 351 QGFFVSVFYCFFNGEVRSALRKR 373
Cdd:cd15256   236 QGFFIFLFHCLLNSEVRAAFKHK 258
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
114-376 8.37e-23

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: 96.64  E-value: 8.37e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 114 RIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNItwFLLQLIDhevHEGNEVWCRCVTTIFNY 193
Cdd:cd15439     2 LALTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQLSLCLFLADL--LFLVGID---RTDNKVLCSIIAGFLHY 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 194 FVVTNFFWMFVEGCYLHTAI----VMTYSTEH-LRKWLFLFIGWCIPCpIIVAWAVG---KLYYENEQCWFGKEPGDLvd 265
Cdd:cd15439    77 LFLACFAWMFLEAVHLFLTVrnlkVVNYFSSHrFKKRFMYPVGYGLPA-VIVAISAAvnpQGYGTPKHCWLSMEKGFI-- 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 266 YIYQGPIILVLLINFVFLFNIVRILMTKLrASTTSETIQYRK----AVKATLVLLpLLGITYMLFFVNPGEDDlsqIVFI 341
Cdd:cd15439   154 WSFLGPVCVIIVINLVLFCLTLWILREKL-SSLNAEVSTLKNtrllTFKAIAQLF-ILGCTWILGLFQVGPVA---TVMA 228
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 1937369810 342 YFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15439   229 YLFTITNSLQGVFIFLVHCLLNRQVREEYRRWITG 263
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
118-372 8.99e-23

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: 96.76  E-value: 8.99e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQLIDHevheGNEVWCRCVTTIFNYFVVT 197
Cdd:cd15438     6 LITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLI-FLLGINNT----NNQVACAVVAGLLHYFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPI--IVAWAVGKLYYENEQCWFGKEPGDLVDYIyqGPIILV 275
Cdd:cd15438    81 AFCWMSLEGVELYLMVVQVFNTQSLKKRYLLLIGYGVPLVIvaISAAVNSKGYGTQRHCWLSLERGFLWSFL--GPVCLI 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 276 LLINFVFLFNIVRILMTKLrASTTSETIQYRKAVKATLVL---LPLLGITYMLFFVNPGEddlSQIVFIYFNSFLQSFQG 352
Cdd:cd15438   159 ILVNAIIFVITVWKLAEKF-SSINPDMEKLRKIRALTITAiaqLCILGCTWIFGFFQFSD---STLVMSYLFTILNSLQG 234
                         250       260
                  ....*....|....*....|
gi 1937369810 353 FFVSVFYCFFNGEVRSALRK 372
Cdd:cd15438   235 LFIFLLHCLLSKQVREEYSR 254
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
113-372 3.21e-22

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: 94.88  E-value: 3.21e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQLIDHEvhegNEVWCRCVTTIFN 192
Cdd:cd15252     1 YNILTRITQVGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFLAELV-FLIGINTTT----NKIFCSVIAGLLH 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPII-VAWAVGKLYYENEQ-CWFGKEPGDLVDYIyqG 270
Cdd:cd15252    76 YFFLAAFAWMFIEGIQLYLMLVEVFENEGSRHKNFYIFGYGSPAVIVgVSAALGYRYYGTTKvCWLSTENYFIWSFI--G 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 271 PIILVLLINFVFLFNIVRILM--TKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEddlSQIVFIYFNSFLQ 348
Cdd:cd15252   154 PATLIILLNLIFLGVAIYKMFrhTAGLKPEVSCLENIRSWARGAIALLFLLGLTWIFGVLHINH---ASVVMAYLFTVSN 230
                         250       260
                  ....*....|....*....|....
gi 1937369810 349 SFQGFFVSVFYCFFNGEVRSALRK 372
Cdd:cd15252   231 SLQGMFIFLFHCVLSRKVRKEYYK 254
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
118-372 7.96e-22

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: 94.15  E-value: 7.96e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNitwFLLQLidHEVHEGNEVWCRCVTTIFNYFVVT 197
Cdd:cd15255     6 TLSFIGCGVSLCALIVTFILFLAVGVPKSERTTVHKNLIFALAAAE---FLLMF--SEWAKGNQVACWAVTALLHLFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKL--YYENEQCWFGKEPGdlVDYIYQGPIILV 275
Cdd:cd15255    81 AFSWMLVEGLLLWSKVVAVNMSEDRRMKFYYVTGWGLPVVIVAVTLATSFnkYVADQHCWLNVQTD--IIWAFVGPVLFV 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 276 LLINFVFLFNIVRILMTKLRASTTSET----------IQYRKAVKATLVLLPLLGITYMLffvnpGEDDLSQIVFIYFNS 345
Cdd:cd15255   159 LTVNTFVLFRVVMVTVSSARRRAKMLTpssdlekqigIQIWATAKPVLVLLPVLGLTWLC-----GVLVHLSDVWAYVFI 233
                         250       260
                  ....*....|....*....|....*..
gi 1937369810 346 FLQSFQGFFVSVFYCFFNGEVRSALRK 372
Cdd:cd15255   234 TLNSFQGLYIFLVYAIYNSEVRNAIQR 260
HormR smart00008
Domain present in hormone receptors;
36-107 4.02e-21

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 86.41  E-value: 4.02e-21
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937369810   36 PYSYCNTTLDQIgTCWPQSAPGALVERPCPEYFNGIKYNTTrnAYRECLENGTWASR-VNYSHCEPILDDKQR 107
Cdd:smart00008   1 TDLGCPATWDGI-ICWPQTPAGQLVEVPCPKYFSGFSYKTG--ASRNCTENGGWSPPfPNYSNCTSNDYEELK 70
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
118-371 1.99e-20

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: 89.91  E-value: 1.99e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQLIDHEvhegNEVWCRCVTTIFNYFVVT 197
Cdd:cd15991     6 IITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELI-FLIGINQTE----NPFVCTVVAILLHYFYMS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAI--VMTYSTEHLRkwLFLFIGWCIPCpIIVAWAVG---KLYYENEQCWFGKEpgDLVDYIYQGPI 272
Cdd:cd15991    81 TFAWMFVEGLHIYRMLteVRNINTGHMR--FYYVVGWGIPA-IITGLAVGldpQGYGNPDFCWLSVQ--DTLIWSFAGPI 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 273 ILVLLINFVFLfnIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSqivFIYFNSFLQSFQG 352
Cdd:cd15991   156 GIVVIINTVIF--VLAAKASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLLGLMAVNSDTLS---FHYLFAIFSCLQG 230
                         250
                  ....*....|....*....
gi 1937369810 353 FFVSVFYCFFNGEVRSALR 371
Cdd:cd15991   231 IFIFFFHCIFNKEVRKHLK 249
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
119-376 6.22e-20

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: 88.66  E-value: 6.22e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 119 INYLGHCVSVVALVAAFLLF-LVLRSIrcLRNVIHW-------NLITTFILRNiTWFLLQLIDHEVHEGNevWCRCVTTI 190
Cdd:cd15253     7 LSQVGLGASILALLLCLGIYrLVWRSV--VRNKISYfrhmtlvNIAFSLLLAD-TCFLGATFLSAGHESP--LCLAAAFL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 191 FNYFVVTNFFWMFVEGCYLHTAIVMTYstEHLRKWLFL----FIGWCipCPIIVAWAVGKLYYENEQ------CWFGKEP 260
Cdd:cd15253    82 CHFFYLATFFWMLVQALMLFHQLLFVF--HQLAKRSVLplmvTLGYL--CPLLIAAATVAYYYPKRQylhegaCWLNGES 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 261 GDLvdYIYQGPIILVLLINFVFLFnivrILMTKLRASTTSET--IQYRKA----VKATLVLLPLLGITYMLFFVNPGEDd 334
Cdd:cd15253   158 GAI--YAFSIPVLAIVLVNLLVLF----VVLMKLMRPSVSEGppPEERKAllsiFKALLVLTPVFGLTWGLGVATLTGE- 230
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937369810 335 lSQIVFIYFNSFLQSFQGFFVSVFYCFFNGEVRSALRKRWHR 376
Cdd:cd15253   231 -SSQVSHYGFAILNAFQGVFILLFGCLMDKKVREALLKRLCK 271
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
118-376 1.79e-19

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: 87.28  E-value: 1.79e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNItwFLLQLIDHEvheGNEVWCRCVTTIFNYFVVT 197
Cdd:cd16007     6 VITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAEL--LFLIGIDKT---QYQIACPIFAGLLHFFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPII-VAWAVGKLYYENEQ-CWFGKEPGDLVDYIyqGPIILV 275
Cdd:cd16007    81 AFSWLCLEGVQLYLMLVEVFESEYSRKKYYYLCGYCFPALVVgISAAIDYRSYGTEKaCWLRVDNYFIWSFI--GPVSFV 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 276 LLINFVFLFNIVRILM--TKLRASTTSETIQYRKAVKATLVLLPLLGITYM--LFFVNPgeddlSQIVFIYFNSFLQSFQ 351
Cdd:cd16007   159 IVVNLVFLMVTLHKMIrsSSVLKPDSSRLDNIKSWALGAITLLFLLGLTWAfgLLFINK-----ESVVMAYLFTTFNAFQ 233
                         250       260
                  ....*....|....*....|....*
gi 1937369810 352 GFFVSVFYCffngevrsALRKRWHR 376
Cdd:cd16007   234 GMFIFIFHC--------ALQKKVHK 250
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
37-101 6.38e-19

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: 80.11  E-value: 6.38e-19
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937369810  37 YSYCNTTLDQIgTCWPQSAPGALVERPCPEYFNGIKYNttRNAYRECLENGTWASR--VNYSHCEPI 101
Cdd:pfam02793   1 GLGCPRTWDGI-LCWPRTPAGETVEVPCPDYFSGFDPR--GNASRNCTEDGTWSEHppSNYSNCTSN 64
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
118-372 1.63e-18

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: 84.49  E-value: 1.63e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNitwflLQLIDHEVHEGNEVWCRCVTTIFNYFVVT 197
Cdd:cd15931     6 WINRVGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSMSH-----TLFLAGIEYVENELACTVMAGLLHYLFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAI-----VMTYSTEHLRKWLFLFIGWCIPCPIIVAWAV--GKLYYENEQCWFGKEPGDLvdYIYQG 270
Cdd:cd15931    81 SFVWMLLEALQLHLLVrrltkVQVIQRDGLPRPLLCLIGYGVPFLIVGVSALvySDGYGEAKMCWLSQERGFN--WSFLG 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 271 PIILVLLINFVFLFNIVRILMTKLrASTTSETIQYRKAVKATLVL---LPLLGITYM--LFFVNPgeddlSQIVFIYFNS 345
Cdd:cd15931   159 PVIAIIGINWILFCATLWCLRQTL-SNMNSDISQLKDTRLLTFKAvaqLFILGCTWVlgLFQTNP-----VALVFQYLFT 232
                         250       260
                  ....*....|....*....|....*..
gi 1937369810 346 FLQSFQGFFVSVFYCFFNGEVRSALRK 372
Cdd:cd15931   233 ILNSLQGAFLFLVHCLLNKEVREEYIK 259
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
114-376 1.67e-17

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: 81.69  E-value: 1.67e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 114 RIALIINYLGHCVSVVALVAAFLLFLVLRSIR-CLRNVIHWNLITTFILRNITWFLLQLIdheVHEGNEVWCRCVTTIFN 192
Cdd:cd15258     2 HILTFISYVGCGISAIFLAITILTYIAFRKLRrDYPSKIHMNLCAALLLLNLAFLLSSWI---ASFGSDGLCIAVAVALH 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIVMTYSTeHLRKWLFLF--IGWCIPC--PIIVAWAVGKLYY-------ENEQ----CWFG 257
Cdd:cd15258    79 YFLLACLTWMGLEAFHLYLLLVKVFNT-YIRRYILKLclVGWGLPAllVTLVLSVRSDNYGpitipngEGFQndsfCWIR 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 258 KepgDLVDYIY-QGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEddlS 336
Cdd:cd15258   158 D---PVVFYITvVGYFGLTFLFNMVMLATVLVQICRLREKAQATPRKRALHDLLTLLGLTFLLGLTWGLAFFAWGP---F 231
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1937369810 337 QIVFIYFNSFLQSFQGFFVSVFYCffngEVRSALRKRWHR 376
Cdd:cd15258   232 NLPFLYLFAIFNSLQGFFIFIWYC----SMKENVRKQWRA 267
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
115-373 1.80e-17

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


Pssm-ID: 320379  Cd Length: 253  Bit Score: 81.53  E-value: 1.80e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 115 IALIINYLGHCVSVVALVAAFLLFLvlRSIRCLRNVIHWNLITTFILRNITWFLLQLIDHevhegNEVWCRCVTTIFNYF 194
Cdd:cd15251     6 VTLIVGCGVSCLALLTLLAIYAAFW--RYIRSERSIILINFCLSIISSNILILVGQTQTL-----NKGVCTMTAAFLHFF 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 195 VVTNFFWMFVEGCYLHTAIVMTYSTEHLRKwLFLFIGWCIPCpIIVAWAVG----KLYYENEQCWFGKEPGDLvdYIYQG 270
Cdd:cd15251    79 FLSSFCWVLTEAWQSYMAVTGRMRTRLIRK-RFLCLGWGLPA-LVVAVSVGftrtKGYGTSSYCWLSLEGGLL--YAFVG 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 271 PIILVLLINFVFLFNIVRILMTKLRASTTSETiqyrkAVKATLVLLPLLGITYM--LFFVNPGEDDLSQIVFIYFNSFlq 348
Cdd:cd15251   155 PAAAVVLVNMVIGILVFNKLVSRDGISDNAMA-----SLWSSCVVLPLLALTWMsaVLAMTDRRSVLFQILFAVFDSL-- 227
                         250       260
                  ....*....|....*....|....*
gi 1937369810 349 sfQGFFVSVFYCFFNGEVRSALRKR 373
Cdd:cd15251   228 --QGFVIVMVHCILRREVQDAVKCR 250
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
118-372 6.33e-17

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: 79.96  E-value: 6.33e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNL-ITTFILRNITWFLLQLIDHEVHegnevwCRCVTTIFNYFVV 196
Cdd:cd16006     6 VITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLcINLFIAEFIFLIGIDKTEYKIA------CPIFAGLLHFFFL 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 197 TNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPII-VAWAVGKLYYENEQ-CWFGKEPGDLVDYIyqGPIIL 274
Cdd:cd16006    80 AAFAWMCLEGVQLYLMLVEVFESEYSRKKYYYVAGYLFPATVVgVSAAIDYKSYGTEKaCWLRVDNYFIWSFI--GPVTF 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 275 VLLINFVFL----FNIVRILMTKLRASTTSETIqyRKAVKATLVLLPLLGITYM--LFFVNPgeddlSQIVFIYFNSFLQ 348
Cdd:cd16006   158 IILLNLIFLvitlCKMVKHSNTLKPDSSRLENI--KSWVLGAFALLCLLGLTWSfgLLFINE-----ETIVMAYLFTIFN 230
                         250       260
                  ....*....|....*....|....
gi 1937369810 349 SFQGFFVSVFYCFFNGEVRSALRK 372
Cdd:cd16006   231 AFQGMFIFIFHCALQKKVRKEYSK 254
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
118-371 1.54e-15

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: 76.20  E-value: 1.54e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLF-LVLRS-----IRCLRNVIHWNLITTFILRNItWFLL--QLIDHEVHEGNevwCRCVTT 189
Cdd:cd15932     6 YITYVGLGISILSLVLCLIIEaLVWKSvtknkTSYMRHVCLVNIALSLLIADI-WFIIgaAISTPPNPSPA---CTAATF 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 190 IFNYFVVTNFFWMFVEGCYLHTAIVMTYSteHLRKWLFLFIGWCIP--CPIIVA------WAVGKLYYENEQCWFG-KEP 260
Cdd:cd15932    82 FIHFFYLALFFWMLTLGLLLFYRLVLVFH--DMSKSTMMAIAFSLGygCPLIIAiitvaaTAPQGGYTRKGVCWLNwDKT 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 261 GDLVDYIyqGPIILVLLINFVflfnIVRILMTKLRASTTSE--TIQYRKA----VKATLVLLPLLGITYM--LFFVNPGE 332
Cdd:cd15932   160 KALLAFV--IPALAIVVVNFI----ILIVVIFKLLRPSVGErpSKDEKNAlvqiGKSVAILTPLLGLTWGfgLGTMIDPK 233
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937369810 333 DDLSQIVFIYFNSFlqsfQGFFVSVFYCFFNGEVRSALR 371
Cdd:cd15932   234 SLAFHIIFAILNSF----QGFFILVFGTLLDSKVREALL 268
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
118-367 1.89e-15

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: 75.75  E-value: 1.89e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNL-ITTFILRNITWFLLQLIDHEVHegnevwCRCVTTIFNYFVV 196
Cdd:cd16005     6 VITWVGILLSLVCLLICIFTFCFFRGLQSDRNTIHKNLcISLFVAELLFLIGINRTDQPIA------CAVFAALLHFFFL 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 197 TNFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPII-VAWAVGKLYYENEQ-CWFGKEPGDLVDYIyqGPIIL 274
Cdd:cd16005    80 AAFTWMFLEGVQLYIMLVEVFESEHSRRKYFYLVGYGMPALIVaVSAAVDYRSYGTDKvCWLRLDTYFIWSFI--GPATL 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 275 VLLINFVFLFNIVRILM--TKLRASTTSETIQYRKAVKATLVLLPLLGITYM--LFFVNPgeddlSQIVFIYFNSFLQSF 350
Cdd:cd16005   158 IIMLNVIFLGIALYKMFhhTAILKPESGCLDNIKSWVIGAIALLCLLGLTWAfgLMYINE-----STVIMAYLFTIFNSL 232
                         250
                  ....*....|....*..
gi 1937369810 351 QGFFVSVFYCFFNGEVR 367
Cdd:cd16005   233 QGMFIFIFHCVLQKKVR 249
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
114-375 6.00e-15

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: 74.31  E-value: 6.00e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 114 RIALIINYLGHCVSVVALVAAFLLFLVLRSIRclRNV---IHWNLITTFILRNITwFLLQ--LIDHEvhegNEVWCRCVT 188
Cdd:cd15997     2 RILTLITYLGCGISSIFLGITLVTYLAFEKLR--RDYpskILINLCTALLMLNLV-FLLNswLSSFN----NYGLCITVA 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 189 TIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTeHLRKWLFLF--IGWCIPCPII-VAWAVGKLYYENEQ-----------C 254
Cdd:cd15997    75 AFLHYFLLASFTWMGLEAVHMYFALVKVFNI-YIPNYILKFciAGWGIPAVVVaLVLAINKDFYGNELssdslhpstpfC 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 255 WFGKepgDLVDYI-YQGPIILVLLINfVFLFNIVRILMTKLRASTTSETIQ--YRKAVKATLVLLPLLGITYMLFFVNPG 331
Cdd:cd15997   154 WIQD---DVVFYIsVVAYFCLIFLCN-ISMFITVLIQIRSMKAKKPSRNWKqgFLHDLKSVASLTFLLGLTWGFAFFAWG 229
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937369810 332 EddlSQIVFIYFNSFLQSFQGFFVSVFYCFFNGEVrsalRKRWH 375
Cdd:cd15997   230 P---VRIFFLYLFSICNTLQGFFIFVFHCLMKENV----RKQWR 266
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
118-369 6.21e-15

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: 74.11  E-value: 6.21e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQLidHEVHegNEVWCRCVTTIFNYFVVT 197
Cdd:cd15993     6 IVTYSSVSASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELL-FLLGI--NRTE--NQFLCTVVAILLHYFFLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCpIIVAWAVG---KLYYENEQCWFGKEpgDLVDYIYQGPIIL 274
Cdd:cd15993    81 TFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPA-IITGLAVGldpEGYGNPDFCWISIH--DKLVWSFAGPIVV 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 275 VLLINFVFLFNIVRILMTKLRASTTSETIQyrKAVKATLVLLPLLGITYM--LFFVNPgeddlSQIVFIYFNSFLQSFQG 352
Cdd:cd15993   158 VIVMNGVMFLLVARMSCSPGQKETKKTSVL--MTLRSSFLLLLLISATWLfgLLAVNN-----SVLAFHYLHAILCCLQG 230
                         250
                  ....*....|....*..
gi 1937369810 353 FFVSVFYCFFNGEVRSA 369
Cdd:cd15993   231 LAVLLLFCVLNEEVQEA 247
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
113-367 2.06e-14

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: 72.60  E-value: 2.06e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 113 YRIALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQLidheVHEGNEVWCRCVTTIFN 192
Cdd:cd15437     1 YNVLTRITQLGIIISLICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELI-FLIGI----NMNANKLFCSIIAGLLH 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIV-MTYSTEHLRKWLFLFiGWCIPCPII-VAWAVGKLYY-ENEQCWFGKEPGDLVDYIyq 269
Cdd:cd15437    76 YFFLAAFAWMCIEGIHLYLIVVgVIYNKGFLHKNFYIF-GYGSPAVVVgISAALGYKYYgTTKVCWLSTENNFIWSFI-- 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 270 GPIILVLLINF----VFLFNIVRILMTKLRASTTSETIqyRKAVKATLVLLPLLGITYM---LFFVNpgeddlSQIVFIY 342
Cdd:cd15437   153 GPACLIILVNLlafgVIIYKVFRHTAMLKPEVSCYENI--RSCARGALALLFLLGATWIfgvLHVVY------GSVVTAY 224
                         250       260
                  ....*....|....*....|....*
gi 1937369810 343 FNSFLQSFQGFFVSVFYCFFNGEVR 367
Cdd:cd15437   225 LFTISNAFQGMFIFIFLCVLSRKIQ 249
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
118-368 3.63e-14

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: 72.60  E-value: 3.63e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLR-NVIHWNLITTFILRNITWFL--------LQLIDHEVHEGNEV------ 182
Cdd:cd15257     6 IISTIGCVLSIAGLVITIIFHLHTRKLRKSSvTWVLLNLCSSLLLFNIIFTSgventnndYEISTVPDRETNTVllseey 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 183 ------WCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTehLRKWLFLF---IGWCIPCpIIVAWAVGKLYYEN-- 251
Cdd:cd15257    86 vepdtdVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKP--LPEMFILQasaIGWGIPA-VVVAITLGATYRFPts 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 252 -----------EQCWFGKEPGDLVdyiYQGPII--LVLLINFVFLFNIVRILMT------KLRASTTSETIQYRKAVKAT 312
Cdd:cd15257   163 lpvftrtyrqeEFCWLAALDKNFD---IKKPLLwgFLLPVGLILITNVILFIMTsqkvlkKNNKKLTTKKRSYMKKIYIT 239
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937369810 313 LVLLPLLGITYMLFFVNPGEDDLSQIVFIYFNSFLQSFQGFFVSVFYCFFNGEVRS 368
Cdd:cd15257   240 VSVAVVFGITWILGYLMLVNNDLSKLVFSYIFCITNTTQGVQIFILYTWRTPEFRK 295
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
118-367 1.19e-13

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: 70.59  E-value: 1.19e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQlIDHEVHEgneVWCRCVTTIFNYFVVT 197
Cdd:cd15436     6 VITWVGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFIAELL-FLIG-INRTQYT---IACPIFAGLLHFFFLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCPII-VAWAVGKLYYENEQ-CWFGKEPGDLVDYIyqGPIILV 275
Cdd:cd15436    81 AFCWLCLEGVQLYLLLVEVFESEYSRRKYFYLCGYSFPALVVaVSAAIDYRSYGTEKaCWLRVDNYFIWSFI--GPVTFV 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 276 LLINFVF----LFNIVRILMTKLRASTTSETIqyRKAVKATLVLLPLLGITYM--LFFVNPgeddlSQIVFIYFNSFLQS 349
Cdd:cd15436   159 ITLNLVFlvitLHKMVSHSDLLKPDSSRLDNI--KSWALGAIALLFLLGLTWSfgLMFINE-----ESVVMAYLFTIFNA 231
                         250
                  ....*....|....*...
gi 1937369810 350 FQGFFVSVFYCFFNGEVR 367
Cdd:cd15436   232 FQGVFIFIFHCALQKKVR 249
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
122-373 5.09e-13

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: 68.94  E-value: 5.09e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 122 LGHCVSVVALVAAFLLFLVL-RSIRCLRNVIHWNLITTFILRNITWFLLQLIDHevhegNEVWCRCVTTIFNYFVVTNFF 200
Cdd:cd15989    12 VGCGLSCLALITLAVVYAALwRYIRSERSIILINFCLSIISSNILILVGQTQTH-----NKGICTMTTAFLHFFFLASFC 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 201 WMFVEGCYLHTAIVMTYSTEHLRKwLFLFIGWCIPCpIIVAWAVG----KLYYENEQCWFGKEPGDLvdYIYQGPIILVL 276
Cdd:cd15989    87 WVLTEAWQSYMAVTGKIRTRLIRK-RFLCLGWGLPA-LVVAISMGftkaKGYGTPHYCWLSLEGGLL--YAFVGPAAAVV 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 277 LINFV---FLFNIV----RILMTKLR----------------------ASTTSETIQYRKAVKATL----VLLPLLGITY 323
Cdd:cd15989   163 LVNMVigiLVFNKLvsrdGILDKKLKhragqmsephsgltlkcakcgvVSTTALSATTASNAMASLwsscVVLPLLALTW 242
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937369810 324 M--LFFVNPGEDDLSQIVFIYFNsflqSFQGFFVSVFYCFFNGEVRSALRKR 373
Cdd:cd15989   243 MsaVLAMTDKRSILFQILFAVFD----SLQGFVIVMVHCILRREVQDAFRCR 290
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
122-373 2.65e-12

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: 66.55  E-value: 2.65e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 122 LGHCVSVVALVAAFLLFL-VLRSIRCLRNVIHWNLITTFILRNITWFLLQlidheVHEGNEVWCRCVTTIFNYFVVTNFF 200
Cdd:cd15990    13 VGCGVSSLTLLLLIIIYVsVWRYIRSERSVILINFCLSIISSNALILIGQ-----TQTRNKVVCTLVAAFLHFFFLSSFC 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 201 WMFVEGCYLHTAIVMTYSTEHLRKwLFLFIGWCIPCpIIVAWAVG----KLYYENEQCWFGKEPGDLvdYIYQGPIILVL 276
Cdd:cd15990    88 WVLTEAWQSYMAVTGRLRNRIIRK-RFLCLGWGLPA-LVVAISVGftkaKGYGTVNYCWLSLEGGLL--YAFVGPAAAVV 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 277 LINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYM--LFFVNPGEDDLSQIVFIYFNsflqSFQGFF 354
Cdd:cd15990   164 LVNMVIGILVFNKLVSKDGITDKKLKERAGASLWSSCVVLPLLALTWMsaVLAITDRRSALFQILFAVFD----SLEGFV 239
                         250
                  ....*....|....*....
gi 1937369810 355 VSVFYCFFNGEVRSALRKR 373
Cdd:cd15990   240 IVMVHCILRREVQDAVKCR 258
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
115-371 8.95e-12

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


Pssm-ID: 320654 [Multi-domain]  Cd Length: 291  Bit Score: 65.36  E-value: 8.95e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 115 IALIINYLGHCVSVVALVAAFLLFLvlRSIRCLRNVIHWNLITTFILRNItwflLQLIDHEVHEGNEVwCRCVTTIFNYF 194
Cdd:cd15988     6 VPLMIGCAVSCMALLILLAIYAAFW--RFIRSERSIILLNFCLSILASNI----LILVGQSQTLSKGV-CTMTAAFLHFF 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 195 VVTNFFWMFVEGCYLHTAIVMTYSTEHLRKwLFLFIGWCIPCpIIVAWAVG----KLYYENEQCWFGKEPGDLvdYIYQG 270
Cdd:cd15988    79 FLSSFCWVLTEAWQSYLAVIGRMRTRLVRK-RFLCLGWGLPA-LVVAVSVGftrtKGYGTASYCWLSLEGGLL--YAFVG 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 271 PIILVLLINFVFLFNIVRILMT---------KLRA---------------------STTSETIQYRKAVK---ATLVLLP 317
Cdd:cd15988   155 PAAVIVLVNMLIGIIVFNKLMSrdgisdkskKQRAgseaepcsslllkcskcgvvsSAAMSSATASSAMAslwSSCVVLP 234
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937369810 318 LLGITYM--LFFVNPGEDDLSQIVFIYFNsflqSFQGFFVSVFYCFFNGEVRSALR 371
Cdd:cd15988   235 LLALTWMsaVLAMTDRRSILFQVLFAVFN----SVQGFVIITVHCFLRREVQDVVK 286
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
118-374 1.12e-11

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: 64.94  E-value: 1.12e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSircLRNvIHWNLITTFILRNITWFLLQLIDHEVHEGNEVWCRCVTTIFNYFVVT 197
Cdd:cd15039     6 ILTLIGLIISLVFLLLTLAVYALLPE---LRN-LHGKCLMCLVLSLFVAYLLLLIGQLLSSGDSTLCVALGILLHFFFLA 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLH-----TAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAV---------GKLYYENEQCWFGkEPGDL 263
Cdd:cd15039    82 AFFWLNVMSFDIWrtfrgKRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIvdfspntdsLRPGYGEGSCWIS-NPWAL 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 264 VDYIYqGPIILVLLINFV-FLFNIVRILMTKlraSTTSETIQYRKAVKATLV----LLPLLGITYMLFFVNPGEDDLSQI 338
Cdd:cd15039   161 LLYFY-GPVALLLLFNIIlFILTAIRIRKVK---KETAKVQSRLRSDKQRFRlylkLFVIMGVTWILEIISWFVGGSSVL 236
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937369810 339 --VFIYFNsflqSFQGFFvsVFYCF-FNGEVRSALRKRW 374
Cdd:cd15039   237 wyIFDILN----GLQGVF--IFLIFvCKRRVLRLLKKKI 269
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
126-361 4.10e-11

orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR97 is an orphan receptor that has been classified into the group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR112, GPR114, and GPR126. GPR97 is identified as a lymphatic adhesion receptor that is specifically expressed in lymphatic endothelium, but not in blood vascular endothelium, and is shown to regulate migration of lymphatic endothelial cells via the small GTPases RhoA and cdc42. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320558 [Multi-domain]  Cd Length: 277  Bit Score: 63.28  E-value: 4.10e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 126 VSVVALVAAFLLFLVLRSIR---CLRNV--IHWNLITTFILRNITWFLLQLIDHEVHEGNevwCRCVTTIFNYFVVTNFF 200
Cdd:cd15442    14 VSMVFLIFTIILYFFLRFTYqkfKSEDApkIHVNLSSSLLLLNLAFLLNSGVSSRAHPGL---CKALGGVTHYFLLCCFT 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 201 WMFVEGCYLH---TAIVMTYSTEHLRKwlFLFIGWCIPCPIIVAWAVGKLY--YENEQ---------CWFgKEPGDLVDY 266
Cdd:cd15442    91 WMAIEAFHLYllaIKVFNTYIHHYFAK--LCLVGWGFPALVVTITGSINSYgaYTIMDmanrttlhlCWI-NSKHLTVHY 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 267 IY-QGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQivfIYFNS 345
Cdd:cd15442   168 ITvCGYFGLTFLFNTVVLGLVAWKIFHLQSATAGKEKCQAWKGGLTVLGLSCLLGVTWGLAFFTYGSMSVPT---VYIFA 244
                         250
                  ....*....|....*.
gi 1937369810 346 FLQSFQGFFVSVFYCF 361
Cdd:cd15442   245 LLNSLQGLFIFIWFVI 260
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
114-376 1.72e-10

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: 61.44  E-value: 1.72e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 114 RIALIINYLGHCVSVVALVAAFLLFLVLRSIRC-LRNVIHWNLITTFILRNITwFLLQ--LIDHEVHEgnevWCRCVTTI 190
Cdd:cd15996     2 RVLTFITYIGCGISAIFSAATLLTYIAFEKLRRdYPSKILMNLSTALLFLNLV-FLLDgwIASFEIDE----LCITVAVL 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 191 FNYFVVTNFFWMFVEGCYLHTAIVMTYSTeHLRKWL--FLFIGWCIPCPII-VAWAV-----GKLYYE--------NEQC 254
Cdd:cd15996    77 LHFFLLATFTWMGLEAIHMYIALVKVFNT-YIRRYIlkFCIIGWGLPALIVsIVLAStndnyGYGYYGkdkdgqggDEFC 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 255 WFgkePGDLVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYR--KAVKATLVLLPLLGITYMLFFVNPGE 332
Cdd:cd15996   156 WI---KNPVVFYVTCAAYFGIMFLMNVAMFIVVMVQICGRNGKRSNRTLREEilRNLRSVVSLTFLLGMTWGFAFFAWGP 232
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937369810 333 DDLSqivFIYFNSFLQSFQGFFVSVFYCffngEVRSALRKRWHR 376
Cdd:cd15996   233 VNLA---FMYLFTIFNSLQGLFIFVFHC----ALKENVQKQWRR 269
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
115-377 4.32e-10

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


Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 60.22  E-value: 4.32e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 115 IALIINYLGHCVSVVALVAAFLLFLVLRSIRC-LRNVIHWNLITTFILRNITWFLLQLIdhEVHEGNEVWCRCVTTIFNY 193
Cdd:cd15444     3 ILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRdYPSKILIQLCVALLLLNLVFLLDSWI--ALYKDIVGLCISVAVFLHY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 194 FVVTNFFWMFVEGCYLHTAIVMTYSTeHLRKWL--FLFIGWCIPC-PIIVAWAVGKLYY------------ENEQCWFGK 258
Cdd:cd15444    81 FLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYIlkFCIVGWGVPAvVVAIVLAVSKDNYglgsygkspngsTDDFCWINN 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 259 epgDLVDYI----YQGPIILVLLINF-VFLFNIVRILMTKLRASTTSETIQYRKAVKAtlvLLPLLGITYMLFFVNPGED 333
Cdd:cd15444   160 ---NIVFYItvvgYFCVIFLLNISMFiVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAG---ITFLLGITWGFAFFAWGPV 233
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937369810 334 DLsqiVFIYFNSFLQSFQGFFVSVFYCFfngeVRSALRKRWHRW 377
Cdd:cd15444   234 NL---AFMYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRRY 270
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
119-360 6.56e-09

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: 56.30  E-value: 6.56e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 119 INYLGHCVSVVALVAAFLLFLVLRS-IRCLRNVIHWNLITTFILRNITwFLLQLIDHEVHEGneVWCRCVTTIFNYFVVT 197
Cdd:cd15443     7 ISIVGCSISAAASLLTILLHFFSRKqPKDSTTRIHMNLLGSLFLLNGS-FLLSPPLATSQST--WLCRAAAALLHYSLLC 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTeHLRKWLFLF--IGWCIPCPIIVAW-------------AVGKLYYENEQCWF-GKEPG 261
Cdd:cd15443    84 CLTWMAIEGFHLYLLLVKVYNI-YIRRYVLKLcvLGWGLPALIVLLVlifkreaygphtiPTGTGYQNASMCWItSSKVH 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 262 DLVDYIYQGpiiLVLLINFVFLFNIVRILmTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQivfI 341
Cdd:cd15443   163 YVLVLGYAG---LTSLFNLVVLAWVVRML-RRLRSRKQELGERARRDWVTVLGLTCLLGTTWALAFFSFGVFLIPQ---L 235
                         250
                  ....*....|....*....
gi 1937369810 342 YFNSFLQSFQGFFVSVFYC 360
Cdd:cd15443   236 FLFTIINSLYGFFICLWYC 254
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
119-371 1.01e-08

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: 56.00  E-value: 1.01e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 119 INYLGHCVSVVALVAAFLLFLVLRS------IRCLRNVIHWNLITTFILRNItWFLLQLIDHEVHEgNEVWCRCVTTIFN 192
Cdd:cd15994     7 ITRIGLGLSIFSLALCLTIEAVVWShvtkteITYMRHVCIVNIATSLLIADV-WFILASIVHNTAL-NYPLCVAATFFLH 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 193 YFVVTNFFWMFVEGCYLHTAIVMTYSTehLRKWLFLFIGWCIP--CPIIVAWAV------GKLYYENEQCWFG-KEPGDL 263
Cdd:cd15994    85 FFYLSLFFWMLTKALLILYGILLVFFK--ITKSVFIATAFSIGygCPLVIAVLTvaitepKKGYLRPEACWLNwDETKAL 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 264 VDYIYqgPIILVLLINF-VFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMlFFVNPGEDDLSQIVFIY 342
Cdd:cd15994   163 LAFII--PALSIVVVNLiVVGVVVVKTQRSSIGESCKQDVSNIIRISKNVAILTPLLGLTWG-FGLATIIDSRSLPFHII 239
                         250       260
                  ....*....|....*....|....*....
gi 1937369810 343 FnSFLQSFQGFFVSVFYCFFNGEVRSALR 371
Cdd:cd15994   240 F-ALLNAFQGFFILLFGTILDRKIRIALY 267
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
118-374 4.72e-08

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: 54.04  E-value: 4.72e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLL-FLVLRSI-----RCLRNVIHWNLITTFILRNItWFLlqlIDHEVHEGNEVWCR--CVTT 189
Cdd:cd15254     6 YITYIGLSISILSLAICIVIeSLVWKSVtknrtSYMRHVCILNIAVSLLIADI-WFI---VVAAIQDQNYAVNGnvCVAA 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 190 IF--NYFVVTNFFWMFVEGCYL--HTAIVMTYSTEHLRKWLFLFIGWCIPCPIIVAWAVGKL----YYENEQCWFGKEPG 261
Cdd:cd15254    82 TFfiHFFYLCVFFWMLALGLMLfyRLVFILHDTSKTIQKAVAFCLGYGCPLIISVITIAVTLprdsYTRKKVCWLNWEDS 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 262 DLVDYIYQGPIILVLLINFVFLFNIVRILMTKL-RASTTSETIQYRKAVKATLVLLPLLGIT--YMLFFVNPGEDDLSQI 338
Cdd:cd15254   162 KALLAFVIPALIIVAVNSIITVVVIVKILRPSIgEKPSKQERSSLFQIIKSIGVLTPLLGLTwgFGLATVIKGSSIVFHI 241
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1937369810 339 VFIYFNSFlqsfQGFFVSVFYCFFNGEVRSALRKRW 374
Cdd:cd15254   242 LFTLLNAF----QGLFILVFGTLWDKKVQEALLNKY 273
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
118-371 1.15e-07

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


Pssm-ID: 320658  Cd Length: 255  Bit Score: 52.52  E-value: 1.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITwFLLQLIDHEvhegNEVWCRCVTTIFNYFVVT 197
Cdd:cd15992     6 TLTWSSVGVTLGFLLLTFLFLLCLRALRSNKTSIRKNGATALFLSELV-FILGINQAD----NPFACTVIAILLHFFYLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 198 NFFWMFVEGCYLHTAIVMTYSTEHLRKWLFLFIGWCIPCpIIVAWAVG---KLYYENEQCWFGKEpgDLVDYIYQGPIIL 274
Cdd:cd15992    81 TFSWLFLEGLHIYRMLSEVRDINYGPMRFYYLIGWGVPA-FITGLAVGldpEGYGNPDFCWLSIY--DTLIWSFAGPVAF 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 275 VLLINfVFLFnivrILMTKLRASTTSETIQYRK----AVKATLVLLPLLGITYMLFFVNPGEDdlsQIVFIYFNSFLQSF 350
Cdd:cd15992   158 AVSMN-VFLY----ILSSRASCSAQQQSFEKKKgpvsGLRTAFTVLLLVSVTCLLALLSVNSD---VILFHYLFAGFNCL 229
                         250       260
                  ....*....|....*....|.
gi 1937369810 351 QGFFVSVFYCFFNGEVRSALR 371
Cdd:cd15992   230 QGPFIFLSHVVLLKEVRKALK 250
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
116-363 9.04e-06

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: 47.04  E-value: 9.04e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 116 ALIINYLGHCVSVVALVAAFLLFLVLRSIRCLRNVIHWNLITTFILRNITWFLLQLID--HEVHEGNEVWCRCVTTIFNY 193
Cdd:cd14964     1 TTIILSLLTCLGLLGNLLVLLSLVRLRKRPRSTRLLLASLAACDLLASLVVLVLFFLLglTEASSRPQALCYLIYLLWYG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 194 FVVTNFFWMFVEGCYLHTAIVMTYS-TEHLRKWLFLFI---GWCIPCPIIVAWAVGKLYYENEQCWFGKEPGDLVDYIYQ 269
Cdd:cd14964    81 ANLASIWTTLVLTYHRYFALCGPLKyTRLSSPGKTRVIilgCWGVSLLLSIPPLVGKGAIPRYNTLTGSCYLICTTIYLT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 270 -----GPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKAT---LVLLPLLGITYMLFFVNPGEDDLSQIVFI 341
Cdd:cd14964   161 wgfllVSFLLPLVAFLVIFSRIVLRLRRRVRAIRSAASLNTDKNLKATkslLILVITFLLCWLPFSIVFILHALVAAGQG 240
                         250       260
                  ....*....|....*....|....*..
gi 1937369810 342 -----YFNSFLQSFQGFFVSVFYCFFN 363
Cdd:cd14964   241 lnllsILANLLAVLASTLNPFIYCLGN 267
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
118-359 6.26e-05

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: 44.44  E-value: 6.26e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 118 IINYLGHCVSVVALVAAFLLFLVLRSIRCLRNV-IHWNLITTFILRNITWFLLQlidHEVHEGNEVWCRCVTTIFNYFVV 196
Cdd:cd15995     6 ILTYVGCIISALASVFTIAFYLCSRRKPRDYTIyVHMNLLLAIFLLDTSFLISE---PLALTGSEAACRAGGMFLHFSLL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 197 TNFFWMFVEGCYLHTAIVMTYSTeHLRKWLFLF--IGWCIPCPII-VAWAVGKLYY---------------ENEQCWFGK 258
Cdd:cd15995    83 ACLTWMGIEGYNLYRLVVEVFNT-YVPHFLLKLcaVGWGLPIFLVtLIFLVDQDNYgpiilavhrspekvtYATICWITD 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 259 EpgdLVDYIYQ-GPIILVLLINFVFLFNIVrILMTKLRASTtsetiQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLsQ 337
Cdd:cd15995   162 S---LISNITNlGLFSLVFLFNMAMLATMV-VEILRLRPRT-----HKWSHVLTLLGLSLVLGIPWALAFFSFASGTF-Q 231
                         250       260
                  ....*....|....*....|..
gi 1937369810 338 IVFIYFNSFLQSFQGFFVSVFY 359
Cdd:cd15995   232 LVIVYLFTIINSLQGFLIFLWY 253
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
180-371 4.03e-03

orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group III adhesion GPCRs include orphan GPR123, GPR124, GPR125, and their 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 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. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 also interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Furthermore, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl.


Pssm-ID: 320387 [Multi-domain]  Cd Length: 260  Bit Score: 38.90  E-value: 4.03e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 180 NEVWCRCVTTIFNYFVVTNFFWMFVEGCYLHTAIVMTYST-------EHLRKWL--FLFIGWCIPCPI--IVAWAVGKLY 248
Cdd:cd15259    66 NQLVCQAVGILLHYSTLCTLLWVGVTARNMYKQVTKTAKPpqdedqpPRPPKPMlrFYLIGWGIPLIIcgITAAVNLDNY 145
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937369810 249 YENEQCWFGKEPGDLVDYiyqGPIILVLLINFVFLFNIVRILmtklRASTTSETIQYRkavkATLVLLPLLGITYMLFFV 328
Cdd:cd15259   146 STYDYCWLAWDPSLGAFY---GPAALIVLVNCIYFLRIYCQL----KGAPVSFQSQLR----GAVITLFLYVAMWACGAL 214
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1937369810 329 NPGEDDLSQIVFIYFNSFLQSFQGFFVSVFYCFFNGEVRSALR 371
Cdd:cd15259   215 AVSQRYFLDLVFSCLYGATCSSLGLFVLIHHCLSREDVRQSWR 257
 
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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