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Conserved domains on  [gi|148225847|ref|NP_001080206|]
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calcitonin gene-related peptide type 1 receptor precursor [Xenopus laevis]

Protein Classification

HRM and 7tmB1_calcitonin_R domain-containing protein (domain architecture ID 12039870)

HRM and 7tmB1_calcitonin_R domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
153-416 3.62e-165

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: 320402  Cd Length: 264  Bit Score: 471.20  E-value: 3.62e-165
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 153 ALNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNPVICKISQF 232
Cdd:cd15274    1 AYNLYYLAIVGHSLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSIIIIIHLVAVVPNGELVARNPVSCKILHF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 233 IHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHLLYIIHGP 312
Cdd:cd15274   81 IHQYMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAVTRAVYYNDNCWLSSETHLLYIIHGP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 313 ICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGRIAEEIYDYVMHILMHYQG 392
Cdd:cd15274  161 IMAALVVNFFFLLNIVRVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQFVLFPWRPSGKILGKIYDYVMHSLIHFQG 240
                        250       260
                 ....*....|....*....|....
gi 148225847 393 LLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15274  241 FFVATIFCFCNGEVQAILKRQWNQ 264
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
77-145 1.07e-24

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


:

Pssm-ID: 308439  Cd Length: 64  Bit Score: 97.84  E-value: 1.07e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 148225847   77 GQFCNRTWDGWLCWGDVAAGIISEQRCPDYFQDFDPSEKVTKECGKNGHWFRHPdsnrtWTNYTRCNTF 145
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDYRGNASRNCTEDGTWSEHP-----PTNYSNCTSN 64
 
Name Accession Description Interval E-value
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
153-416 3.62e-165

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: 320402  Cd Length: 264  Bit Score: 471.20  E-value: 3.62e-165
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 153 ALNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNPVICKISQF 232
Cdd:cd15274    1 AYNLYYLAIVGHSLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSIIIIIHLVAVVPNGELVARNPVSCKILHF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 233 IHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHLLYIIHGP 312
Cdd:cd15274   81 IHQYMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAVTRAVYYNDNCWLSSETHLLYIIHGP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 313 ICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGRIAEEIYDYVMHILMHYQG 392
Cdd:cd15274  161 IMAALVVNFFFLLNIVRVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQFVLFPWRPSGKILGKIYDYVMHSLIHFQG 240
                        250       260
                 ....*....|....*....|....
gi 148225847 393 LLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15274  241 FFVATIFCFCNGEVQAILKRQWNQ 264
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
153-395 2.77e-86

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, characteristic 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: 306508  Cd Length: 244  Bit Score: 268.35  E-value: 2.77e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847  153 ALNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNPVI-CKISQ 231
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRAILFLVGDAVLFNGEDLDHCSWKVgCKVVA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847  232 FIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHLLYIIHG 311
Cdd:pfam00002  81 VFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERLYLWWYLLIGWGVPALVVGIWAGVKGYGEDDGCWLSNENGLWWIIKG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847  312 PICAALLVNLFFLLNIVRVLITKLKVTHQAESNLY-MKAVRATLILVPLLGIEFVLFPWKPEgRIAEEIYDYVMHILMHY 390
Cdd:pfam00002 161 PVLLVILVNFIIFINIVRILVQKLRETNMGESDLYqRRLAKSTLLLLPLLGITWVLFAFNPD-NVLRVVFLYLFLILNSF 239

                  ....*
gi 148225847  391 QGLLV 395
Cdd:pfam00002 240 QGFFV 244
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
77-145 1.07e-24

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


Pssm-ID: 308439  Cd Length: 64  Bit Score: 97.84  E-value: 1.07e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 148225847   77 GQFCNRTWDGWLCWGDVAAGIISEQRCPDYFQDFDPSEKVTKECGKNGHWFRHPdsnrtWTNYTRCNTF 145
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDYRGNASRNCTEDGTWSEHP-----PTNYSNCTSN 64
HormR smart00008
Domain present in hormone receptors;
79-151 2.83e-19

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 83.33  E-value: 2.83e-19
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 148225847    79 FCNRTWDGWLCWGDVAAGIISEQRCPDYFQDFDPSEKVTKECGKNGHWFRHPdsnrtwTNYTRCNTFTHEKVK 151
Cdd:smart00008   4 GCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTGASRNCTENGGWSPPF------PNYSNCTSNDYEELK 70
 
Name Accession Description Interval E-value
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
153-416 3.62e-165

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: 320402  Cd Length: 264  Bit Score: 471.20  E-value: 3.62e-165
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 153 ALNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNPVICKISQF 232
Cdd:cd15274    1 AYNLYYLAIVGHSLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSIIIIIHLVAVVPNGELVARNPVSCKILHF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 233 IHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHLLYIIHGP 312
Cdd:cd15274   81 IHQYMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAVTRAVYYNDNCWLSSETHLLYIIHGP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 313 ICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGRIAEEIYDYVMHILMHYQG 392
Cdd:cd15274  161 IMAALVVNFFFLLNIVRVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQFVLFPWRPSGKILGKIYDYVMHSLIHFQG 240
                        250       260
                 ....*....|....*....|....
gi 148225847 393 LLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15274  241 FFVATIFCFCNGEVQAILKRQWNQ 264
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
154-416 1.05e-104

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 (Alzhemer'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: 320169  Cd Length: 273  Bit Score: 316.86  E-value: 1.05e-104
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVAT-------NPVI 226
Cdd:cd15041    2 LAVIYIYLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFISFILRAIFWILWDLLVVYDRLTSSGvetvlmqNPVG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 227 CKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWIS-SETHL 305
Cdd:cd15041   82 CKLLSVLKRYFKSANYFWMLVEGLYLHRLIVVAFFSEPSSLKLYYAIGWGLPLVIVVAWAIVRALLSDESCWIGyNNGHY 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 306 LYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPE-GRIAEEIYDYVM 384
Cdd:cd15041  162 EWILYGPNLLALLVNLFFLINILRILLTKLRSHPNAEPSNYRKAVKATLVLIPLFGIQYLLTIYRPPdGSEGELVYEYFN 241
                        250       260       270
                 ....*....|....*....|....*....|..
gi 148225847 385 HILMHYQGLLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15041  242 AILNSSQGFFVAVIYCFLNGEVQSELKRKYSR 273
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
153-395 2.77e-86

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, characteristic 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: 306508  Cd Length: 244  Bit Score: 268.35  E-value: 2.77e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847  153 ALNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNPVI-CKISQ 231
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRAILFLVGDAVLFNGEDLDHCSWKVgCKVVA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847  232 FIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHLLYIIHG 311
Cdd:pfam00002  81 VFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERLYLWWYLLIGWGVPALVVGIWAGVKGYGEDDGCWLSNENGLWWIIKG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847  312 PICAALLVNLFFLLNIVRVLITKLKVTHQAESNLY-MKAVRATLILVPLLGIEFVLFPWKPEgRIAEEIYDYVMHILMHY 390
Cdd:pfam00002 161 PVLLVILVNFIIFINIVRILVQKLRETNMGESDLYqRRLAKSTLLLLPLLGITWVLFAFNPD-NVLRVVFLYLFLILNSF 239

                  ....*
gi 148225847  391 QGLLV 395
Cdd:pfam00002 240 QGFFV 244
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
158-416 7.31e-84

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  Cd Length: 267  Bit Score: 262.98  E-value: 7.31e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 158 YLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNPVICkisQFIHL-- 235
Cdd:cd15260    6 YVYIGGYSVSLIALIISLAIFFSFRSLRCTRITIHMNLFISFALNNLLWIVWYKLVVDNPEVLLENPIWC---QALHVll 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 236 -YLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDN--CWIsSETHLLYIIHGP 312
Cdd:cd15260   83 qYFMVCNYFWMFCEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLPDDTerCWM-EESSYQWILIVP 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 313 ICAALLVNLFFLLNIVRVLITKLKVT-HQAESNLYMKAVRATLILVPLLGIEFVLFPWKPE-GRIAEEIYDYVMHILMHY 390
Cdd:cd15260  162 VVLSLLINLIFLINIVRVLLTKLRATsPNPAPAGLRKAVRATLILIPLLGLQFLLIPFRPEpGAPLETIYQYVSALLTSL 241
                        250       260
                 ....*....|....*....|....*.
gi 148225847 391 QGLLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15260  242 QGLCVAVLFCFCNGEVIAAIKRKWRR 267
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
151-415 4.67e-58

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  Cd Length: 265  Bit Score: 195.33  E-value: 4.67e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 151 KTALNLYYLtiiGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQAlvATNPVICKIS 230
Cdd:cd15264    2 KVALIIYYL---GFSISLVALAVALIIFLYFRSLRCLRNNIHCNLIVTFILRNVTWFIMQNTLTEIHH--QSNQWVCRLI 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 231 QFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWI--SSETHLLYI 308
Cdd:cd15264   77 VTVYNYFQVTNFFWMFVEGLYLHTMIVWAYSADKIRFWYYIVIGWCIPCPFVLAWAIVKLLYENEHCWLpkSENSYYDYI 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 309 IHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKP-EGRIAEEIYDYVMHIL 387
Cdd:cd15264  157 YQGPILLVLLINFIFLFNIVWVLITKLRASNTLETIQYRKAVKATLVLLPLLGITYMLFFINPgDDKTSRLVFIYFNTFL 236
                        250       260
                 ....*....|....*....|....*...
gi 148225847 388 MHYQGLLVATIFCFFNGEVQAVLKRHWN 415
Cdd:cd15264  237 QSFQGLFVAVFYCFLNGEVRSAIRKKFS 264
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
155-415 8.73e-53

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  Cd Length: 285  Bit Score: 182.20  E-value: 8.73e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 155 NLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITII-----------SLSAVANNQALVATN 223
Cdd:cd15272    3 SIRLMYNIGYGLSLVSLLIAVIIMLYFKKLHCPRNTIHINLFVSFILRAVLSFIkenllvqgvgfPGDVYYDSNGVIEFK 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 224 PVI----CKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCW- 298
Cdd:cd15272   83 DEGshweCKLFFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLLFVLPWVFVRATLEDTLCWn 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 299 ISSETHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTH--QAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGR-- 374
Cdd:cd15272  163 TNTNKGYFWIIRGPIVISIAINFLFFINIVRVLFTKLKASNtqESRPFRYRKLAKSTLVLIPLFGVHYMVFVVLPDSMss 242
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 148225847 375 -IAEEIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKRHWN 415
Cdd:cd15272  243 dEAELVWLYFEMFFNSFQGFIVALLFCFLNGEVQSEIKKKWQ 284
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
155-415 5.41e-52

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  Cd Length: 289  Bit Score: 179.88  E-value: 5.41e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 155 NLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSI--------------------ITIISLSAVA 214
Cdd:cd15265    3 RLYLIYTVGYSISLVSLTVAVFILGYFRRLHCTRNYIHMHLFVSFMLRAVsifvkdavlysgsgldelerPSMEDLKSIV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 215 NNQALVATNPVICKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYN 294
Cdd:cd15265   83 EAPPVDKSQYVGCKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVFVIPWASVRATLAD 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 295 DNCWISSETHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAE---SNLYMKAVRATLILVPLLGIEFVLFPWKP 371
Cdd:cd15265  163 TRCWDLSAGNYKWIYQVPILAAIVVNFILFLNIVRVLATKLRETNAGRcdtRQQYRKLAKSTLVLIPLFGVHYIVFMGMP 242
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 148225847 372 --EGRIAEEIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKRHWN 415
Cdd:cd15265  243 ytEVGLLWQIRMHYELFFNSFQGFFVAIIYCFCNGEVQAEIKKRWE 288
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
157-414 8.00e-51

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  Cd Length: 270  Bit Score: 176.48  E-value: 8.00e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 157 YYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAV-------ANNQALVATNPVICKI 229
Cdd:cd15262    5 YRFHVAALSVSVVTSLPAVFIFYSYKRLRITRVILHRNLLISIIIRNILVIISKVFVildaltsSGDDTVMNQNAVVCRL 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 230 SQFIHLYLMGCNYFWMLCEGIYLHTLIVvAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHLLYII 309
Cdd:cd15262   85 LSIFERAARNAVFACMFVEGFYLHRLIV-AVFAEKSSIRFLYVIGAVLPLFPVIIWAIIRALHNDHSCWVVDIEGVQWVL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 310 HGPICAALLVNLFFLLNIVRVLITKLKvtHQAESNLYMKAVRATLILVPLLGIEFVLFPWKP--EGRIAEEIYDYVMHIL 387
Cdd:cd15262  164 DTPRLFILLVNTVLLVDIIRVLVTKLR--NTEENSQTKSTTRATLFLVPLFGLHFVITAYRPstDDCDWEDIYYYANYLI 241
                        250       260
                 ....*....|....*....|....*..
gi 148225847 388 MHYQGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15262  242 EGLQGFLVAILFCYINKEVHYLIKNTY 268
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
159-416 8.18e-50

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  Cd Length: 285  Bit Score: 174.10  E-value: 8.18e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 159 LTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVAT---------------- 222
Cdd:cd15273    7 ISQIGYIVSLITLIIAFAIFLSFKKLHCARNKLHMHLFASFILRAFMTLLKDSLFIDGLGLLADiverngggnevianig 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 223 NPVICKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSE 302
Cdd:cd15273   87 SNWVCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVPWIVARILFENSLCWTTNS 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 303 THLLY-IIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFP----WKPEGRIAE 377
Cdd:cd15273  167 NLLNFlIIRIPIMISVLINFILFLNIVRVLLVKLRSSVNEDSRRYKKWAKSTLVLVPLFGVHYTIFLilsyLDDTNEAVE 246
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 148225847 378 EIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15273  247 LIWLFCDQLFASFQGFFVALLYCFLNGEVRAEIQRKWRR 285
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
153-414 8.86e-49

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 (Alzhemer's and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression).


Pssm-ID: 320389  Cd Length: 282  Bit Score: 171.01  E-value: 8.86e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 153 ALNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITII-----------SLSAVANNQALVA 221
Cdd:cd15261    1 ARGTRTLEIVGLCLSLVSLIISLFIFSYFRTLRNHRTRIHKNLFLAILLQVIIRLVlyidqaitrsrGSHTNAATTEGRT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 222 TN--PVICKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDN-CW 298
Cdd:cd15261   81 INstPILCEGFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAIVTLIKMKVNrCW 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 299 IS-SETHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIE--FVLFPWKPEGRI 375
Cdd:cd15261  161 FGyYLTPYYWILEGPRLAVILINLFFLLNIIRVLVSKLRESHSREIEQVRKAVKAAIVLLPLLGITniLQMIPPPLTSVI 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 148225847 376 AE-EIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15261  241 VGfAVWSYSTHFLTSFQGFFVALIYCFLNGEVKNVLKKFW 280
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
156-414 1.55e-48

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  Cd Length: 272  Bit Score: 170.24  E-value: 1.55e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYltiIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAvannQALVATNPVICKISQFIHL 235
Cdd:cd15263    7 IYF---IGYSLSLVALSLALWIFLYFKDLRCLRNTIHTNLMFTYILADLTWILTLTL----QVSIGEDQKSCIILVVLLH 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 236 YLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLY------------YNDNCWISSET 303
Cdd:cd15263   80 YFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYAFIGWGIPAVVIVIWAIVKALAptapntaldpngLLKHCPWMAEH 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 304 HLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGRIAEEIYDYV 383
Cdd:cd15263  160 IVDWIFQGPAILVLAVNLVFLVRIMWVLITKLRSANTVETQQYRKAAKALLVLIPLLGITYILVIAGPTEGIAANIFEYV 239
                        250       260       270
                 ....*....|....*....|....*....|.
gi 148225847 384 MHILMHYQGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15263  240 RAVLLSTQGFTVALFYCFLNTEVRNTLRHHF 270
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
152-415 9.21e-48

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  Cd Length: 280  Bit Score: 168.38  E-value: 9.21e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 152 TALNLYYltIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITII-------SLSAVANNQA-----L 219
Cdd:cd15266    2 LTLQLIY--TIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIkdivlysTYSKRPDDETgwisyL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 220 VATNPVICKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWI 299
Cdd:cd15266   80 SEESSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVVPWGVAKILLENTGCWG 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 300 SSETH-LLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKP----EGR 374
Cdd:cd15266  160 RNENMgIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYKYRLARSTLVLIPLLGIHEVVFSFITdeqvEGF 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 148225847 375 iAEEIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKRHWN 415
Cdd:cd15266  240 -SRHIRLFIQLTLSSFQGFLVAVLYCFANGEVKAELKKRWQ 279
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
162-416 1.31e-47

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  Cd Length: 271  Bit Score: 167.61  E-value: 1.31e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 162 IGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATN--PVICKISQFIHLYLMG 239
Cdd:cd15275   10 VGYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFIKDAVLFSSEDDNHCDiyTVGCKVAMVFSNYCIM 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 240 CNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCW-ISSETHLLYIIHGPICAALL 318
Cdd:cd15275   90 ANYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFIISWAIARYLHENEGCWdTRRNAWIWWIIRGPVILSIF 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 319 VNLFFLLNIVRVLITKLKV--THQAESNLYMKAVRATLILVPLLGIEFVLFPWKPE--GRIAEEIYDYVMHILMHYQGLL 394
Cdd:cd15275  170 VNFILFLNILRILMRKLRApdMRGNEFSQYKRLAKSTLLLIPLFGLHYILFAFFPEdvSSGTMEIWLFFELALGSFQGFV 249
                        250       260
                 ....*....|....*....|..
gi 148225847 395 VATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15275  250 VAVLYCFLNGEVQLEIQRKWRR 271
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
156-416 1.81e-47

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  Cd Length: 290  Bit Score: 167.82  E-value: 1.81e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSI--------------------ITIISLSAVAN 215
Cdd:cd15984    4 LYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVsifvkdavlysgsaleemerITEEDLKSITE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 216 NQALVATNPVICKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYND 295
Cdd:cd15984   84 APPADKAQFVGCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVRATLADT 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 296 NCWISSETHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNL---YMKAVRATLILVPLLGIEFVLFPWKPE 372
Cdd:cd15984  164 GCWDLSAGNLKWIIQVPILAAIVVNFILFINIVRVLATKLRETNAGRCDTrqqYRKLLKSTLVLMPLFGVHYIVFMAMPY 243
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 148225847 373 GRIAEEIYDYVMHILM---HYQGLLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15984  244 TEVSGILWQVQMHYEMlfnSFQGFFVAIIYCFCNGEVQAEIKKSWSR 290
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
163-414 8.17e-47

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  Cd Length: 267  Bit Score: 165.29  E-value: 8.17e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 163 GHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQAL--VATNPVICKISQFIHLYLMGC 240
Cdd:cd15271   11 GYGTSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALAVFIKDAVLFADESVdhCTMSTVACKAAVTFFQFCVLA 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 241 NYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHLLYIIHGPICAALLVN 320
Cdd:cd15271   91 NFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVWVLTRLQYDNRGCWDDLESRIWWIIKTPILLSVFVN 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 321 LFFLLNIVRVLITKLKVT--HQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEgRIAEEIYDYVMHILMHYQGLLVATI 398
Cdd:cd15271  171 FLIFINVIRILVQKLKSPdvGGNDTSHYMRLAKSTLLLIPLFGVHYVVFAFFPE-HVGVEARLYFELVLGSFQGFIVALL 249
                        250
                 ....*....|....*.
gi 148225847 399 FCFFNGEVQAVLKRHW 414
Cdd:cd15271  250 YCFLNGEVQAEIKKRL 265
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
162-416 8.69e-47

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  Cd Length: 268  Bit Score: 165.30  E-value: 8.69e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 162 IGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNP--VICKISQFIHLYLMG 239
Cdd:cd15930   10 VGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKDAVLFSSEDVDHCFVstVGCKASMVFFQYCVM 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 240 CNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCW-ISSETHLLYIIHGPICAALL 318
Cdd:cd15930   90 ANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVWIVARLYFEDTGCWdINDESPYWWIIKGPILISIL 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 319 VNLFFLLNIVRVLITKLKV--THQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEgRIAEEIYDYVMHILMHYQGLLVA 396
Cdd:cd15930  170 VNFVLFINIIRILLQKLRSpdIGGNESSQYKRLARSTLLLIPLFGIHYIVFAFFPE-NISLGIRLYFELCLGSFQGFVVA 248
                        250       260
                 ....*....|....*....|
gi 148225847 397 TIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15930  249 VLYCFLNGEVQAEIKRKWRS 268
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
162-414 2.06e-45

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  Cd Length: 268  Bit Score: 161.56  E-value: 2.06e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 162 IGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANN--QALVATNPVICKISQFIHLYLMG 239
Cdd:cd15269   10 IGHSLSLISLTAAMIILCLFRKLHCTRNYIHMHLFMSFILRAIAVFIKDAVLFESgeEDHCSVASVGCKAAMVFFQYCIM 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 240 CNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCW-ISSETHLLYIIHGPICAALL 318
Cdd:cd15269   90 ANFFWLLVEGLYLHTLLAVSFFSERKYFWWYILIGWGAPSVFITAWSVARIYFEDVGCWdTIIESLLWWIIKTPILVSIL 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 319 VNLFFLLNIVRVLITKLKVTH--QAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGrIAEEIYDYVMHILMHYQGLLVA 396
Cdd:cd15269  170 VNFILFICIIRILVQKLHSPDigRNESSQYSRLAKSTLLLIPLFGIHYIMFAFFPDN-FKAEVKLVFELILGSFQGFVVA 248
                        250
                 ....*....|....*...
gi 148225847 397 TIFCFFNGEVQAVLKRHW 414
Cdd:cd15269  249 VLYCFLNGEVQAELKRKW 266
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
156-414 1.23e-44

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: 320595  Cd Length: 279  Bit Score: 159.92  E-value: 1.23e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCN--SIITIISL--------------SAVANNQAL 219
Cdd:cd15929    4 LQVMYTVGYSLSLAALVLALLILLGLRKLHCTRNYIHANLFASFILRalSVLVKDALlprryskrpdqenwWMLLSNEAS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 220 VAtnpviCKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWI 299
Cdd:cd15929   84 LG-----CRVAQVLMQYCVGANYYWLLVEGLYLHTLLVLAVLSERSLFRLYLLLGWGAPVLFVVPWGIVRYLYENTGCWT 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 300 SSETH-LLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGR---I 375
Cdd:cd15929  159 RNENMaIWWIIRGPILLAILINFFIFLRILKILVSKLRANQMCFRDYKYRLAKSTLTLIPLLGVHEVVFAFVTDEQargT 238
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 148225847 376 AEEIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15929  239 LRYIKLFFELFLSSFQGFLVAVLYCFANKEVQSELRKKW 277
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
156-414 6.85e-43

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 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  Cd Length: 285  Bit Score: 155.47  E-value: 6.85e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIIS---LSAVANNQAL------------V 220
Cdd:cd15983    4 LHLMYTIGYSISLAALLVAVCILCYFKRLHCTRNYIHIHLFASFICRAGSIFVKdavLYSGTNEGEAldekiefglspgT 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 221 ATNPVICKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWIS 300
Cdd:cd15983   84 RLQWVGCKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVRVSLADTQCWDL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 301 SETHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESN---LYMKAVRATLILVPLLGIEFVLFPWKPEGRIAE 377
Cdd:cd15983  164 SAGNLKWIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKLDprqQYRKLLKSTLVLMPLFGVHYVLFMAMPYTDVTG 243
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 148225847 378 EIYDYVMHILMHY---QGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15983  244 LLWQIQMHYEMLFnssQGFFVAFIYCFCNGEVQAEIKKAW 283
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
154-414 7.87e-41

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  Cd Length: 268  Bit Score: 148.96  E-value: 7.87e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQ--ALVATNPVICKISQ 231
Cdd:cd15987    2 LSVKALYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQdsDHCFVSTVECKAVM 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 232 FIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARsLYYND-NCWISSE-THLLYII 309
Cdd:cd15987   82 VFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLR-LHFDDtGCWDMNDnTALWWVI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 310 HGPICAALLVNLFFLLNIVRVLITKLKVTHQA--ESNLYMKAVRATLILVPLLGIEFVLFPWKPEGRIAEEIYDYVMHiL 387
Cdd:cd15987  161 KGPVVGSIMINFVLFIGIIIILVQKLQSPDIGgnESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELG-L 239
                        250       260
                 ....*....|....*....|....*..
gi 148225847 388 MHYQGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15987  240 GSFQGFVVAVLYCFLNGEVQSEIKRKW 266
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
156-416 3.34e-39

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  Cd Length: 289  Bit Score: 145.08  E-value: 3.34e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSF------------VCNSIITIISLSAVANN--QALVA 221
Cdd:cd15982    4 LYIMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFmlraasifvkdkVVHTHIGVKELDAVLMNdfQNAVD 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 222 TNPVI------CKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYND 295
Cdd:cd15982   84 APPVDksqyvgCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAAWAVVRATLADA 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 296 NCWISSETHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNL---YMKAVRATLILVPLLGIEFVLFPWKPE 372
Cdd:cd15982  164 RCWELSAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWETNAVGYDTrkqYRKLAKSTLVLVLVFGVHYIVFVCLPH 243
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 148225847 373 G--RIAEEIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15982  244 TftGLGWEIRMHCELFFNSFQGFFVSIIYCYCNGEVQTEIKKTWTR 289
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
151-416 1.52e-38

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  Cd Length: 264  Bit Score: 142.79  E-value: 1.52e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 151 KTALNLYYLtiiGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIIsLSAVANNqaLVATNPVICKIS 230
Cdd:cd15446    2 KIALIINYL---GHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFL-LQMIDHN--IHESNEVWCRCI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 231 QFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSE--THLLYI 308
Cdd:cd15446   76 TTIYNYFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYENEQCWFGKEpgKYIDYI 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 309 IHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKP-EGRIAEEIYDYVMHIL 387
Cdd:cd15446  156 YQGPVILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPgEDDISQIVFIYFNSFL 235
                        250       260
                 ....*....|....*....|....*....
gi 148225847 388 MHYQGLLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15446  236 QSFQGFFVSVFYCFLNGEVRSAARKRWHR 264
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
162-414 5.52e-38

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  Cd Length: 268  Bit Score: 141.09  E-value: 5.52e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 162 IGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNP--VICKISQFIHLYLMG 239
Cdd:cd15270   10 VGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFIKDAALFQEDDTDHCSMstVLCKVSVVFCHYCVM 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 240 CNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCW-ISSETHLLYIIHGPICAALL 318
Cdd:cd15270   90 TNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCKLYFEDTECWdINNDSPYWWIIKGPIVISVG 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 319 VNLFFLLNIVRVLITKL--KVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEgRIAEEIYDYVMHILMHYQGLLVA 396
Cdd:cd15270  170 VNFLLFLNIIRILLKKLdpRQINFNNSAQYRRLSKSTLLLIPLFGTHYIIFNFLPD-YAGLGIRLYLELCLGSFQGFIVA 248
                        250
                 ....*....|....*...
gi 148225847 397 TIFCFFNGEVQAVLKRHW 414
Cdd:cd15270  249 VLYCFLNQEVQTEISRKW 266
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
159-416 2.32e-37

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  Cd Length: 265  Bit Score: 139.30  E-value: 2.32e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 159 LTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVC-NSIITIISLSAvanNQALVATNPVICKISQFIHLYL 237
Cdd:cd15445    7 INYLGHCISLVALLVAFVLFLRLRSIRCLRNIIHWNLITAFILrNATWFVVQLTM---SPEVHQSNVVWCRLVTAAYNYF 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 238 MGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHLL--YIIHGPICA 315
Cdd:cd15445   84 HVTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFICIGWCIPFPIIVAWAIGKLYYDNEKCWFGKRAGVYtdYIYQGPMIL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 316 ALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKP-EGRIAEEIYDYVMHILMHYQGLL 394
Cdd:cd15445  164 VLLINFIFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPgEDEISRIVFIYFNSFLESFQGFF 243
                        250       260
                 ....*....|....*....|..
gi 148225847 395 VATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15445  244 VSVFYCFLNSEVRSAVRKRWHR 265
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
159-414 2.03e-35

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  Cd Length: 280  Bit Score: 134.29  E-value: 2.03e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 159 LTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITII-----------SLSAVANNQALVATNPVI- 226
Cdd:cd15985    7 LYTVGYTLSLLTLVSALLILTSIRKLHCTRNYIHANLFASFILRAVSVIVkdtllerrwgrEIMRVADWGELLSHKAAIg 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 227 CKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSET-HL 305
Cdd:cd15985   87 CRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVLFVVPWMLAKYLKENKECWALNENmAY 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 306 LYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGR---IAEEIYDY 382
Cdd:cd15985  167 WWIIRIPILLASLINLLIFMRILKVILSKLRANQKGYADYKLRLAKATLTLIPLFGIHEVVFIFATDEQttgILRYIKVF 246
                        250       260       270
                 ....*....|....*....|....*....|..
gi 148225847 383 VMHILMHYQGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15985  247 FTLFLNSFQGFLVAVLYCFANKEVKSELLKKW 278
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
162-414 6.42e-35

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  Cd Length: 269  Bit Score: 132.62  E-value: 6.42e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 162 IGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIIS----LSAVANNQALVATNPVICKISQFIHLYL 237
Cdd:cd15986   10 LGHSVSLIALTTGSTILCLFRKLHCTRNYIHLNLFFSFILRAISVLVKddilYSSSNTEHCTVPPSLIGCKVSLVILQYC 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 238 MGCNYFWMLCEGIYLHTLIVVaVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSETHL-LYIIHGPICAA 316
Cdd:cd15986   90 IMANFYWLLVEGLYLHTLLVV-IFSENRHFIVYLLIGWGIPTVFIIAWIVARIYLEDTGCWDTNDHSVpWWVIRIPIIIS 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 317 LLVNLFFLLNIVRVLITKLKVTHQA--ESNLYMKAVRATLILVPLLGIEFVLFPWKPEGrIAEEIYDYVMHILMHYQGLL 394
Cdd:cd15986  169 IILNFILFISIIRILLQKLRSPDVGgnDQSQYKRLAKSTLLLIPLFGVHYIVFVYFPDS-SSSNYQIFFELCLGSFQGLV 247
                        250       260
                 ....*....|....*....|
gi 148225847 395 VATIFCFFNGEVQAVLKRHW 414
Cdd:cd15986  248 VAILYCFLNSEVQGELKRKW 267
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
162-414 2.94e-34

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  Cd Length: 281  Bit Score: 130.71  E-value: 2.94e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 162 IGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCN--SIITIISLSAVANNQALVATNPVI---------CKIS 230
Cdd:cd15267   12 VGYSLSLGALLLALAILGGFSKLHCMRNYIHMNLFASFILKalSVLVIDALLKTRYSQKIGDDLSSTwlsdeavagCRAA 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 231 QFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWISSET-HLLYII 309
Cdd:cd15267   92 TVFMQYGIVANYCWLLVEGIYLHNLLVLAVFSERSYFSLYLCIGWGAPMLFLVPWVVVKYLYENIQCWSSNDNmGFWWIL 171
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 310 HGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEG------RIAEEIYDYv 383
Cdd:cd15267  172 RFPVFLAILINFFIFVRIIQILVSKLRAHQMRYTDYKFRLAKSTLTLIPLLGIHEVVFAFVTDEhaqgtlRLVKLFFDL- 250
                        250       260       270
                 ....*....|....*....|....*....|.
gi 148225847 384 mhILMHYQGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15267  251 --FLSSFQGLLVAVLYCFVNKEVQSELRKRW 279
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
156-410 1.21e-32

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  Cd Length: 252  Bit Score: 125.52  E-value: 1.21e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAvannqalvATNPVICKISQFIHL 235
Cdd:cd15933    4 LSIISYIGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILLLAGEWA--------EGNKVACKVVAILLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 236 YLMGCNYFWMLCEGIYLHTLIvVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYY--NDNCWISSETHLLYIIHGPI 313
Cdd:cd15933   76 FFFMAAFSWMLVEGLHLYLMI-VKVFNYKSKMRYYYFIGWGLPAIIVAISLAILFDDYgsPNVCWLSLDDGLIWAFVGPV 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 314 CAALLVNLFFLLNIVRVLITK---LKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGriAEEIYDYVMHILMHY 390
Cdd:cd15933  155 IFIITVNTVILILVVKITVSLstnDAKKSQGTLAQIKSTAKASVVLLPILGLTWLFGVLVVNS--QTIVFQYIFVILNSL 232
                        250       260
                 ....*....|....*....|
gi 148225847 391 QGLLVATIFCFFNGEVQAVL 410
Cdd:cd15933  233 QGLMIFLFHCVLNSEVRSAF 252
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
154-416 1.72e-32

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: 320396  Cd Length: 279  Bit Score: 125.85  E-value: 1.72e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAV------ANNQ-----ALVAT 222
Cdd:cd15268    2 LNLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALkwmystAAQQhqwdgLLSYQ 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 223 NPVICKISQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDNCWI-SS 301
Cdd:cd15268   82 DSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFVIPWGIVKYLYEDEGCWTrNS 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 302 ETHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGR---IAEE 378
Cdd:cd15268  162 NMNYWLIIRLPILFAIGVNFLIFIRVICIVISKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHargTLRF 241
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 148225847 379 IYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKRHWNQ 416
Cdd:cd15268  242 VKLFTELSFTSFQGLMVAILYCFVNNEVQMEFRKSWER 279
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
156-407 2.59e-29

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: 320090  Cd Length: 253  Bit Score: 115.75  E-value: 2.59e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSC-QRITLHKNLFFSFVCNSIITIISLSAvannqalvATNPVICK-ISQFI 233
Cdd:cd13952    4 LSIITYVGCGLSLLGLLLTIITYILFRKLRKrKRTKILLNLCLSLLLANLLFLVGISS--------TDNPVGCTaVAALL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 234 HLYLMgCNYFWMLCEGIYLHTLIVVAVFAEKQHLMW-YYLLGWGFPLIPACIHAVARSLYYNDN---CWISSETHLLYII 309
Cdd:cd13952   76 HYFLL-ASFMWMLVEALLLYLRLVKVFGTYPRHFILkYSLIGWGLPLIIVIITAAVDPDSYGGSsgyCWLSNGNGLYYAF 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 310 HGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIE--FVLFPWKPEGRIAEeiydYVMHIL 387
Cdd:cd13952  155 LGPVLLIILINLVIFVLILRKLLRLSAKRNKSERKKTKRQLRAALSLFFLLGLTwiFGILAILGARVVFQ----YLFAIF 230
                        250       260
                 ....*....|....*....|
gi 148225847 388 MHYQGLLVATIFCFFNGEVQ 407
Cdd:cd13952  231 NSLQGFFIFIFYCLRNKEVR 250
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
156-412 2.84e-29

invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors; This subgroup includes latrophilim-like proteins that are found in inveterbrates 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  Cd Length: 259  Bit Score: 115.82  E-value: 2.84e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVannqalvaTNPVICK-ISQFIH 234
Cdd:cd15440    4 LTFITYIGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLCLCLLIAEIVFLLGIDQT--------ENRTLCGvIAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 235 lYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIpacIHAVARSLYYN-----DNCWISSETHLLYII 309
Cdd:cd15440   76 -YFFLAAFSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLFGYGLPAL---IVAVSAGVDPTgygteDHCWLSTENGFIWSF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 310 HGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATL----ILVPLLGIEFVL-FPWKPEGRIaeeIYDYVM 384
Cdd:cd15440  152 VGPVIVVLLANLVFLGMAIYVMCRHSSRSASKKDASKLKNIRGWLkgsiVLVVLLGLTWTFgLLFINQESI---VMAYIF 228
                        250       260
                 ....*....|....*....|....*...
gi 148225847 385 HILMHYQGLLVATIFCFFNGEVQAVLKR 412
Cdd:cd15440  229 TILNSLQGLFIFIFHCVLNEKVRKELRR 256
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
156-407 2.35e-26

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  Cd Length: 253  Bit Score: 107.66  E-value: 2.35e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNL-SCQRITLHKNLFFSFVCNSIITIISLSAvannqalvATNPVICK-ISQFI 233
Cdd:cd15040    4 LSIITYIGCGLSLLGLLLTIITYILFRKLrKRKPTKILLNLCLALLLANLLFLFGINS--------TDNPVLCTaVAALL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 234 HLYLMgCNYFWMLCEGIYLHTLIVVAVFAEKQHLMW-YYLLGWGFPLIPACIHAVARSLYYNDN---CWISSETHLLYII 309
Cdd:cd15040   76 HYFLL-ASFMWMLVEALLLYLRLVKVFGTYPRHFILkYALIGWGLPLIIVIITLAVDPDSYGNSsgyCWLSNGNGLYYAF 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 310 HGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLfpwkpeGRIAEE----IYDYVMH 385
Cdd:cd15040  155 LGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQLRAAVSLFFLLGLTWIF------GILAIFgarvVFQYLFA 228
                        250       260
                 ....*....|....*....|..
gi 148225847 386 ILMHYQGLLVATIFCFFNGEVQ 407
Cdd:cd15040  229 IFNSLQGFFIFIFHCLRNKEVR 250
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
77-145 1.07e-24

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


Pssm-ID: 308439  Cd Length: 64  Bit Score: 97.84  E-value: 1.07e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 148225847   77 GQFCNRTWDGWLCWGDVAAGIISEQRCPDYFQDFDPSEKVTKECGKNGHWFRHPdsnrtWTNYTRCNTF 145
Cdd:pfam02793   1 GLGCPRTWDGILCWPRTPAGETVEVPCPDYFSGFDYRGNASRNCTEDGTWSEHP-----PTNYSNCTSN 64
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
154-414 3.21e-20

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  Cd Length: 254  Bit Score: 90.00  E-value: 3.21e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVAnnqalvatNPVICK-ISQF 232
Cdd:cd15441    2 LLLKIVTYIGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELLFLLGINQTE--------NLFPCKlIAIL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 233 IHLYLMgCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYY--NDNCWISSETHLLYIIH 310
Cdd:cd15441   74 LHYFYL-SAFSWLLVESLHLYRMLTEPRDINHGHMRFYYLLGYGIPAIIVGLSVGLRPDGYgnPDFCWLSVNETLIWSFA 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 311 GPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMkaVRATLILVPLLGIEFVLfpwkpeGRIA----EEIYDYVMHI 386
Cdd:cd15441  153 GPIAFVIVITLIIFILALRASCTLKRHVLEKASVRTD--LRSSFLLLPLLGATWVF------GLLAvnedSELLHYLFAG 224
                        250       260
                 ....*....|....*....|....*...
gi 148225847 387 LMHYQGLLVATIFCFFNGEVQAVLKRHW 414
Cdd:cd15441  225 LNFLQGLFIFLFYCIFNKKVRRELKNAL 252
HormR smart00008
Domain present in hormone receptors;
79-151 2.83e-19

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 83.33  E-value: 2.83e-19
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 148225847    79 FCNRTWDGWLCWGDVAAGIISEQRCPDYFQDFDPSEKVTKECGKNGHWFRHPdsnrtwTNYTRCNTFTHEKVK 151
Cdd:smart00008   4 GCPATWDGIICWPQTPAGQLVEVPCPKYFSGFSYKTGASRNCTENGGWSPPF------PNYSNCTSNDYEELK 70
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
156-411 3.14e-19

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  Cd Length: 260  Bit Score: 87.29  E-value: 3.14e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSC---QRITLHKNLFFSFVCNSIITIISLSAVAnnqalvATNPviCKISQF 232
Cdd:cd15256    4 LSSITYVGCSLSIFCLAITLVTFAVLSSVSTirnQRYHIHANLSFAVLVAQILLLISFRFEP------GTLP--CKIMAI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 233 IHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIpACIHAVARSLYY---NDNCWISSETHLLYII 309
Cdd:cd15256   76 LLHFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGIGWGSPLL-ICIISLTSALDSygeSDNCWLSLENGAIWAF 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 310 HGPICAALLVNLFFLLNIVRVL--ITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGRIAeeIYDYVMHIL 387
Cdd:cd15256  155 VAPALFVIVVNIGILIAVTRVIsrISADNYKVHGDANAFKLTAKAVAVLLPILGSSWVFGVLAVNTHAL--VFQYMFAIF 232
                        250       260
                 ....*....|....*....|....
gi 148225847 388 MHYQGLLVATIFCFFNGEVQAVLK 411
Cdd:cd15256  233 NSLQGFFIFLFHCLLNSEVRAAFK 256
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
156-412 1.32e-16

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  Cd Length: 263  Bit Score: 79.51  E-value: 1.32e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVAtnpvickISQFIHL 235
Cdd:cd15255    4 LRTLSFIGCGVSLCALIVTFILFLAVGVPKSERTTVHKNLIFALAAAEFLLMFSEWAKGNQVACWA-------VTALLHL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 236 YLMGCnYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIpacIHAVARSLYYND-----NCWISSETHLLYIIH 310
Cdd:cd15255   77 FFLAA-FSWMLVEGLLLWSKVVAVNMSEDRRMKFYYVTGWGLPVV---IVAVTLATSFNKyvadqHCWLNVQTDIIWAFV 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 311 GPICAALLVNLFFLLNIVRVLITKLK-----VTHQAESNLYM-----KAVRATLILVPLLGIEF---VLFPWKPegriae 377
Cdd:cd15255  153 GPVLFVLTVNTFVLFRVVMVTVSSARrrakmLTPSSDLEKQIgiqiwATAKPVLVLLPVLGLTWlcgVLVHLSD------ 226
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 148225847 378 eIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKR 412
Cdd:cd15255  227 -VWAYVFITLNSFQGLYIFLVYAIYNSEVRNAIQR 260
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
156-314 4.85e-15

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  Cd Length: 257  Bit Score: 74.85  E-value: 4.85e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAvannqalvATNPVICK-ISQFIH 234
Cdd:cd15252    4 LTRITQVGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFLAELVFLIGINT--------TTNKIFCSvIAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 235 LYLMgCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVARSLYYNDN--CWISSETHLLYIIHGP 312
Cdd:cd15252   76 YFFL-AAFAWMFIEGIQLYLMLVEVFENEGSRHKNFYIFGYGSPAVIVGVSAALGYRYYGTTkvCWLSTENYFIWSFIGP 154

                 ..
gi 148225847 313 IC 314
Cdd:cd15252  155 AT 156
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
156-314 1.11e-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: 320167  Cd Length: 270  Bit Score: 64.94  E-value: 1.11e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLScqriTLHKNLFFSFVCNSIITIISLSAVannQALVATNPVICKISQFIHL 235
Cdd:cd15039    4 LGILTLIGLIISLVFLLLTIAVYALLPELR----NLHGKCLMCLVLSLFVAYLLLLIG---QLLSLGDSTLCVALGILLH 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 236 YLMGCNYFWMLCEGIYLH-----TLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVA---------RSLYYNDNCWISS 301
Cdd:cd15039   77 FFFLAAFFWLNVMSFDIWrtfrsKRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVdfspptdslRPGYGEGSCWISN 156
                        170
                 ....*....|...
gi 148225847 302 ETHLLYIIHGPIC 314
Cdd:cd15039  157 PWALLLYFYGPVA 169
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
154-411 6.55e-11

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  Cd Length: 254  Bit Score: 62.56  E-value: 6.55e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLsavanNQAlvaTNPVICKISQFI 233
Cdd:cd15991    2 LPLKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIGI-----NQT---ENPFVCTVVAIL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 234 HLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGfplIPACIHAVARSL----YYN-DNCWISSETHLLYI 308
Cdd:cd15991   74 LHYFYMSTFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWG---IPAIITGLAVGLdpqgYGNpDFCWLSVQDTLIWS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 309 IHGPIcaALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLfpwkpeGRIAEE----IYDYVM 384
Cdd:cd15991  151 FAGPI--GIVVIINTVIFVLAAKASCGRRQRYFEKSGVISMLRTAFLLLLLISATWLL------GLMAVNsdtlSFHYLF 222
                        250       260
                 ....*....|....*....|....*..
gi 148225847 385 HILMHYQGLLVATIFCFFNGEVQAVLK 411
Cdd:cd15991  223 AIFSCLQGIFIFFFHCIFNKEVRKHLK 249
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
156-312 1.11e-10

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  Cd Length: 258  Bit Score: 61.88  E-value: 1.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLffsfvCNSIITIISLSAVANNQalvATNPVICKI-SQFIH 234
Cdd:cd16005    4 LDVITWVGILLSLVCLLICIFTFCFFRGLQSDRNTIHKNL-----CISLFVAELLFLIGINR---TDQPIACAVfAALLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 235 LYLMGCnYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVA--RSLYYNDNCWISSETHLLYIIHGP 312
Cdd:cd16005   76 FFFLAA-FTWMFLEGVQLYIMLVEVFESEHSRRKYFYLVGYGMPALIVAVSAAVdyRSYGTDKVCWLRLDTYFIWSFIGP 154
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
156-314 6.18e-10

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  Cd Length: 258  Bit Score: 59.50  E-value: 6.18e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSavannqalVATNPVICKISQFIHL 235
Cdd:cd15437    4 LTRITQLGIIISLICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELIFLIGIN--------MNANKLFCSIIAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 236 YLMGCNYFWMLCEGIYLHtLIVVAVFAEKQHLMW-YYLLGWGFPLIPACIHAVARSLYYNDN--CWISSETHLLYIIHGP 312
Cdd:cd15437   76 YFFLAAFAWMCIEGIHLY-LIVVGVIYNKGFLHKnFYIFGYGSPAVVVGISAALGYKYYGTTkvCWLSTENNFIWSFIGP 154

                 ..
gi 148225847 313 IC 314
Cdd:cd15437  155 AC 156
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
154-313 1.47e-09

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


Pssm-ID: 320673  Cd Length: 258  Bit Score: 58.39  E-value: 1.47e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNqalvatnpVICKI-SQF 232
Cdd:cd16007    2 LLLSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLIGIDKTQYQ--------IACPIfAGL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 233 IHLYLMGCnYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVA--RSLYYNDNCWISSETHLLYIIH 310
Cdd:cd16007   74 LHFFFLAA-FSWLCLEGVQLYLMLVEVFESEYSRKKYYYLCGYCFPALVVGISAAIdyRSYGTEKACWLRVDNYFIWSFI 152

                 ...
gi 148225847 311 GPI 313
Cdd:cd16007  153 GPV 155
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
156-412 5.00e-09

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


Pssm-ID: 320597  Cd Length: 262  Bit Score: 56.75  E-value: 5.00e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFfsfVCNSIITIISLSAVANNQalvatNPVICKI-SQFIH 234
Cdd:cd15931    4 LEWINRVGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLC---LCLSMSHTLFLAGIEYVE-----NELACTVmAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 235 LYLMGCnYFWMLCEGIYLHTLIV---VAVFAEKQHL--MWYYLLGWGFPLIPACIHAVARSLYYNDN--CWISSETHLLY 307
Cdd:cd15931   76 YLFLAS-FVWMLLEALQLHLLVRrltKVQVIQRDGLprPLLCLIGYGVPFLIVGVSALVYSDGYGEAkmCWLSQERGFNW 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 308 IIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLymKAVRATLILVP----LLGIEFVLFPWKPEGRIAeeIYDYV 383
Cdd:cd15931  155 SFLGPVIAIIGINWILFCATLWCLRQTLSNMNSDISQL--KDTRLLTFKAVaqlfILGCTWVLGLFQTNPVAL--VFQYL 230
                        250       260
                 ....*....|....*....|....*....
gi 148225847 384 MHILMHYQGLLVATIFCFFNGEVQAVLKR 412
Cdd:cd15931  231 FTILNSLQGAFLFLVHCLLNKEVREEYIK 259
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
154-313 6.03e-09

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  Cd Length: 258  Bit Score: 56.46  E-value: 6.03e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSavannqalvATNP-VICKI-SQ 231
Cdd:cd16006    2 LLLTVITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIGID---------KTEYkIACPIfAG 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 232 FIHLYLMGCnYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWgfpLIPACIHAVARSLYYND-----NCWISSETHLL 306
Cdd:cd16006   73 LLHFFFLAA-FAWMCLEGVQLYLMLVEVFESEYSRKKYYYVAGY---LFPATVVGVSAAIDYKSygtekACWLRVDNYFI 148

                 ....*..
gi 148225847 307 YIIHGPI 313
Cdd:cd16006  149 WSFIGPV 155
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
156-412 7.60e-09

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  Cd Length: 263  Bit Score: 56.20  E-value: 7.60e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFfsfVCNSIITIISLSAVANNQalvatNPVICK-ISQFIH 234
Cdd:cd15439    4 LTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQLS---LCLFLADLLFLVGIDRTD-----NKVLCSiIAGFLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 235 lYLMGCNYFWMLCEGIYLH----TLIVVAVFAEKQHLMWY-YLLGWGFPLIPACIHAVARSLYYN--DNCWISSETHLLY 307
Cdd:cd15439   76 -YLFLACFAWMFLEAVHLFltvrNLKVVNYFSSHRFKKRFmYPVGYGLPAVIVAISAAVNPQGYGtpKHCWLSMEKGFIW 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 308 IIHGPICAALLVNLFFLLNIVRVLITKLkvthqAESNLYMKAVRATLIL-------VPLLGIEFVL--FPWKPEGRIAEe 378
Cdd:cd15439  155 SFLGPVCVIIVINLVLFCLTLWILREKL-----SSLNAEVSTLKNTRLLtfkaiaqLFILGCTWILglFQVGPVATVMA- 228
                        250       260       270
                 ....*....|....*....|....*....|....
gi 148225847 379 iydYVMHILMHYQGLLVATIFCFFNGEVQAVLKR 412
Cdd:cd15439  229 ---YLFTITNSLQGVFIFLVHCLLNRQVREEYRR 259
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
154-315 4.25e-08

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  Cd Length: 258  Bit Score: 54.03  E-value: 4.25e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAvannqalvATNPVICKI-SQF 232
Cdd:cd15436    2 LLLFVITWVGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFIAELLFLIGINR--------TQYTIACPIfAGL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 233 IHLYLMGCnYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIHAVA--RSLYYNDNCWISSETHLLYIIH 310
Cdd:cd15436   74 LHFFFLAA-FCWLCLEGVQLYLLLVEVFESEYSRRKYFYLCGYSFPALVVAVSAAIdyRSYGTEKACWLRVDNYFIWSFI 152

                 ....*
gi 148225847 311 GPICA 315
Cdd:cd15436  153 GPVTF 157
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
166-411 6.32e-08

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  Cd Length: 254  Bit Score: 53.69  E-value: 6.32e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 166 LSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNqalvatnpVICKISQFIHLYLMGCNYFWM 245
Cdd:cd15993   14 ASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLGINRTENQ--------FLCTVVAILLHYFFLSTFAWL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 246 LCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGfplIPACIHAVARSL----YYN-DNCWISSETHLLYIIHGPICAALLVN 320
Cdd:cd15993   86 FVQGLHIYRMQTEARNVNFGAMRFYYAIGWG---VPAIITGLAVGLdpegYGNpDFCWISIHDKLVWSFAGPIVVVIVMN 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 321 LFFLLNIVRVLITKLKvtHQAESNLYMKAVRATLILVPLLGIEFVLfpwkpeGRIAEE----IYDYVMHILMHYQGLLVA 396
Cdd:cd15993  163 GVMFLLVARMSCSPGQ--KETKKTSVLMTLRSSFLLLLLISATWLF------GLLAVNnsvlAFHYLHAILCCLQGLAVL 234
                        250
                 ....*....|....*
gi 148225847 397 TIFCFFNGEVQAVLK 411
Cdd:cd15993  235 LLFCVLNEEVQEAWK 249
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
156-316 6.46e-08

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


Pssm-ID: 320554  Cd Length: 261  Bit Score: 53.61  E-value: 6.46e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAvannqalvATNPVICKISQFIHL 235
Cdd:cd15438    4 LTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLGINN--------TNNQVACAVVAGLLH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 236 YLMGCNYFWMLCEGIYLHtLIVVAVFaEKQHL--MWYYLLGWGFPLIPACIHAVARSLYYND--NCWISSETHLLYIIHG 311
Cdd:cd15438   76 YFFLAAFCWMSLEGVELY-LMVVQVF-NTQSLkkRYLLLIGYGVPLVIVAISAAVNSKGYGTqrHCWLSLERGFLWSFLG 153

                 ....*
gi 148225847 312 PICAA 316
Cdd:cd15438  154 PVCLI 158
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
154-316 1.93e-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: 52.13  E-value: 1.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 154 LNLYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAvannqalvATNPVICKISQFI 233
Cdd:cd15992    2 LPLKTLTWSSVGVTLGFLLLTFLFLLCLRALRSNKTSIRKNGATALFLSELVFILGINQ--------ADNPFACTVIAIL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 234 HLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYLLGWGfplIPACIHAVARSL----YYN-DNCWISSETHLLYI 308
Cdd:cd15992   74 LHFFYLCTFSWLFLEGLHIYRMLSEVRDINYGPMRFYYLIGWG---VPAFITGLAVGLdpegYGNpDFCWLSIYDTLIWS 150

                 ....*...
gi 148225847 309 IHGPICAA 316
Cdd:cd15992  151 FAGPVAFA 158
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
156-410 1.94e-07

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 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. 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  Cd Length: 275  Bit Score: 52.11  E-value: 1.94e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGI-FFYFKNLSCQRITLHK-----NLFFSFVCNSIITIISLSAVANNQALvatNPVICKI 229
Cdd:cd15254    4 LDYITYIGLSISILSLAICIVIeSLVWKSVTKNRTSYMRhvcilNIAVSLLIADIWFIVVAAIQDQNYAV---NGNVCVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 230 SQ-FIHLYLMgCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWY--YLLGWGFPLIPACIHAVA---RSLYYNDN-CWIS-- 300
Cdd:cd15254   81 ATfFIHFFYL-CVFFWMLALGLMLFYRLVFILHDTSKTIQKAvaFCLGYGCPLIISVITIAVtlpRDSYTRKKvCWLNwe 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 301 -SETHLLYIIHGPICAAllvnlfFLLNIVRVLITKL-------KVTHQAESNLYmKAVRATLILVPLLGIE--FVLFPWK 370
Cdd:cd15254  160 dSKALLAFVIPALIIVA------VNSIITVVVIVKIlrpsigeKPSKQERSSLF-QIIKSIGVLTPLLGLTwgFGLATVI 232
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 148225847 371 PEGRIaeeIYDYVMHILMHYQGLLVATIFCFFNGEVQAVL 410
Cdd:cd15254  233 KGSSI---VFHILFTLLNAFQGLFILVFGTLWDKKVQEAL 269
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
161-411 2.30e-07

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: 51.87  E-value: 2.30e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 161 IIGHGLSIASLLISLGIFFYF-KNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNqalvatnpVICKI-SQFIHLYLM 238
Cdd:cd15251    9 IVGCGVSCLALLTLLAIYAAFwRYIRSERSIILINFCLSIISSNILILVGQTQTLNK--------GVCTMtAAFLHFFFL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 239 GcNYFWMLCEGiYLHTLIVVAVFAEKQHLMWYYLLGWGFP-LIPACIHAVARSLYYNDN--CWISSETHLLYIIHGPICA 315
Cdd:cd15251   81 S-SFCWVLTEA-WQSYMAVTGRMRTRLIRKRFLCLGWGLPaLVVAVSVGFTRTKGYGTSsyCWLSLEGGLLYAFVGPAAA 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 316 ALLVNLFFLLNIVRVLITKLKVTHQAESNLYmkavrATLILVPLLGIEFVLFPWKPEGRiAEEIYDYVMHILMHYQGLLV 395
Cdd:cd15251  159 VVLVNMVIGILVFNKLVSRDGISDNAMASLW-----SSCVVLPLLALTWMSAVLAMTDR-RSVLFQILFAVFDSLQGFVI 232
                        250
                 ....*....|....*.
gi 148225847 396 ATIFCFFNGEVQAVLK 411
Cdd:cd15251  233 VMVHCILRREVQDAVK 248
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
156-411 3.33e-07

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 overexpressed 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  Cd Length: 268  Bit Score: 51.54  E-value: 3.33e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIffyfKNLSCQRITLHKNLFFSFVCnsiITIISLSAVANN-----QALVATNPV---IC 227
Cdd:cd15932    4 LDYITYVGLGISILSLVLCLII----EALVWKSVTKNKTSYMRHVC---LVNIALSLLIADiwfiiGAAISTPPNpspAC 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 228 KISQFIHLYLMGCNYFWMLCEGIYL--HTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIH--AVARSLYY--NDNCWIS- 300
Cdd:cd15932   77 TAATFFIHFFYLALFFWMLTLGLLLfyRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITvaATAPQGGYtrKGVCWLNw 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 301 SETHLLYIIHGPICAallvNLFFLLNIVRVLITKL------KVTHQAESNLYMKAVRATLILVPLLGIE-----FVLFPW 369
Cdd:cd15932  157 DKTKALLAFVIPALA----IVVVNFIILIVVIFKLlrpsvgERPSKDEKNALVQIGKSVAILTPLLGLTwgfglGTMIDP 232
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 148225847 370 KPEGriaeeiYDYVMHILMHYQGLLVATIFCFFNGEVQAVLK 411
Cdd:cd15932  233 KSLA------FHIIFAILNSFQGFFILVFGTLLDSKVREALL 268
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
156-402 1.86e-06

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 overexpressed 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  Cd Length: 267  Bit Score: 49.34  E-value: 1.86e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRIT-LHKNLFFS-FVCNSIITIISLSAVANNQALVATNPVickisqFI 233
Cdd:cd15258    4 LTFISYVGCGISAIFLAITILTYIAFRKLRRDYPSkIHMNLCAAlLLLNLAFLLSSWIASFGSDGLCIAVAV------AL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 234 HLYLMGCnYFWMLCEGIYLHtLIVVAVFAE--KQHLMWYYLLGWGFP-LIPACIHAVARSLY------------YNDNCW 298
Cdd:cd15258   78 HYFLLAC-LTWMGLEAFHLY-LLLVKVFNTyiRRYILKLCLVGWGLPaLLVTLVLSVRSDNYgpitipngegfqNDSFCW 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 299 IsSETHLLYI-IHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIE--FVLFPWKPEGRi 375
Cdd:cd15258  156 I-RDPVVFYItVVGYFGLTFLFNMVMLATVLVQICRLREKAQATPRKRALHDLLTLLGLTFLLGLTwgLAFFAWGPFNL- 233
                        250       260
                 ....*....|....*....|....*..
gi 148225847 376 aeeIYDYVMHILMHYQGLLvatIFCFF 402
Cdd:cd15258  234 ---PFLYLFAIFNSLQGFF---IFIWY 254
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
161-411 1.60e-05

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: 46.14  E-value: 1.60e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 161 IIGHGLSIASLLISLGIFF-YFKNLSCQRITLHKNLFFSFVCNSIITIISLSAvannqalvATNPVICK-ISQFIHLYLM 238
Cdd:cd15990   12 IVGCGVSSLTLLLLIIIYVsVWRYIRSERSVILINFCLSIISSNALILIGQTQ--------TRNKVVCTlVAAFLHFFFL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 239 GcNYFWMLCEGiYLHTLIVVAVFAEKQHLMWYYLLGWGFPLIPACIH---AVARSLYYNDNCWISSETHLLYIIHGPICA 315
Cdd:cd15990   84 S-SFCWVLTEA-WQSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISvgfTKAKGYGTVNYCWLSLEGGLLYAFVGPAAA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 316 ALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLFPWKPEGRiAEEIYDYVMHILMHYQGLLV 395
Cdd:cd15990  162 VVLVNMVIGILVFNKLVSKDGITDKKLKERAGASLWSSCVVLPLLALTWMSAVLAITDR-RSALFQILFAVFDSLEGFVI 240
                        250
                 ....*....|....*.
gi 148225847 396 ATIFCFFNGEVQAVLK 411
Cdd:cd15990  241 VMVHCILRREVQDAVK 256
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
156-412 2.30e-05

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  Cd Length: 271  Bit Score: 45.91  E-value: 2.30e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYF------KNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQalvatNPVICKI 229
Cdd:cd15253    4 LDFLSQVGLGASILALLLCLGIYRLVwrsvvrNKISYFRHMTLVNIAFSLLLADTCFLGATFLSAGHE-----SPLCLAA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 230 SQFIH-LYLmgCNYFWMLCEGIYL--HTLIVVAVFAEKQHLMWYYLLGWgfpLIPACIHAVARSLYYNDN-------CWI 299
Cdd:cd15253   79 AFLCHfFYL--ATFFWMLVQALMLfhQLLFVFHQLAKRSVLPLMVTLGY---LCPLLIAAATVAYYYPKRqylhegaCWL 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 300 SSETHLLYIIHGPICAallvNLFFLLNIVRVLITKLKVTHQAESN------LYMKAVRATLILVPLLGIEFVLFPWKPEG 373
Cdd:cd15253  154 NGESGAIYAFSIPVLA----IVLVNLLVLFVVLMKLMRPSVSEGPppeerkALLSIFKALLVLTPVFGLTWGLGVATLTG 229
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 148225847 374 RIAeEIYDYVMHILMHYQGLLVATIFCFFNGEVQAVLKR 412
Cdd:cd15253  230 ESS-QVSHYGFAILNAFQGVFILLFGCLMDKKVREALLK 267
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
161-312 1.26e-04

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  Cd Length: 291  Bit Score: 43.79  E-value: 1.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 161 IIGHGLSIASLLISLGIFFYF-KNLSCQRITLHKNLFFSFVCNSIITIISlsavannQALVATNPVICKISQFIHLYLMG 239
Cdd:cd15988    9 MIGCAVSCMALLILLAIYAAFwRFIRSERSIILLNFCLSILASNILILVG-------QSQTLSKGVCTMTAAFLHFFFLS 81
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 148225847 240 cNYFWMLCEGiYLHTLIVVAVFAEKQHLMWYYLLGWGFP-LIPACIHAVARSLYYNDN--CWISSETHLLYIIHGP 312
Cdd:cd15988   82 -SFCWVLTEA-WQSYLAVIGRMRTRLVRKRFLCLGWGLPaLVVAVSVGFTRTKGYGTAsyCWLSLEGGLLYAFVGP 155
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
153-417 3.16e-04

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 overexpressed 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  Cd Length: 271  Bit Score: 42.12  E-value: 3.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 153 ALNLYYLTIIGHGLSIASLLISLGIFFYFKNLscQRITLHKNLFfsFVCNSIITIISLSAVANNQALVATNPVIC-KISQ 231
Cdd:cd15444    1 MLILTFITYIGCGLSAIFLSVTLVTYIAFEKI--RRDYPSKILI--QLCVALLLLNLVFLLDSWIALYKDIVGLCiSVAV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 232 FIHLYLMgCNYFWMLCEGIYLHtLIVVAVFAE--KQHLMWYYLLGWGFP-LIPACIHAVARSLY------------YNDN 296
Cdd:cd15444   77 FLHYFLL-VSFTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGVPaVVVAIVLAVSKDNYglgsygkspngsTDDF 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 297 CWISSETHLLYIIHGPICAA-LLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIE--FVLFPWKPEG 373
Cdd:cd15444  155 CWINNNIVFYITVVGYFCVIfLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITwgFAFFAWGPVN 234
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 148225847 374 RiaeeIYDYVMHILMHYQGLLVATIFCFfngeVQAVLKRHWNQY 417
Cdd:cd15444  235 L----AFMYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRRY 270
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
156-402 3.66e-04

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  Cd Length: 277  Bit Score: 42.09  E-value: 3.66e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLgIFFYFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATNPVICK-ISQFIH 234
Cdd:cd15442    4 LVTISSAGCGVSMVFLIFTI-ILYFFLRFTYQKFKSEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKaLGGVTH 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 235 LYLMgCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYY-LLGWGFPLIPACIHAVARS--LYYNDN---------CWISSE 302
Cdd:cd15442   83 YFLL-CCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLcLVGWGFPALVVTITGSINSygAYTIMDmanrttlhlCWINSK 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 303 THL-LYI-IHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEF--VLFPWKPEGRIAEe 378
Cdd:cd15442  162 HLTvHYItVCGYFGLTFLFNTVVLGLVAWKIFHLQSATAGKEKCQAWKGGLTVLGLSCLLGVTWglAFFTYGSMSVPTV- 240
                        250       260
                 ....*....|....*....|....
gi 148225847 379 iydYVMHILMHYQGLLvatIFCFF 402
Cdd:cd15442  241 ---YIFALLNSLQGLF---IFIWF 258
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
161-315 3.25e-03

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


Pssm-ID: 320655  Cd Length: 293  Bit Score: 39.28  E-value: 3.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 161 IIGHGLSIASLlISLGIFF--YFKNLSCQRITLHKNLFFSFVCNSIITIISLSAVANNQALVATnpvickiSQFIHLYLM 238
Cdd:cd15989   11 IVGCGLSCLAL-ITLAVVYaaLWRYIRSERSIILINFCLSIISSNILILVGQTQTHNKGICTMT-------TAFLHFFFL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 239 GcNYFWMLCEGiYLHTLIVVAVFAEKQHLMWYYLLGWGFP-LIPACIHAVARSLYYNDN--CWISSETHLLYIIHGPICA 315
Cdd:cd15989   83 A-SFCWVLTEA-WQSYMAVTGKIRTRLIRKRFLCLGWGLPaLVVAISMGFTKAKGYGTPhyCWLSLEGGLLYAFVGPAAA 160
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
156-303 4.52e-03

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


Pssm-ID: 320559  Cd Length: 268  Bit Score: 38.58  E-value: 4.52e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 156 LYYLTIIGHGLSIASLLISLGIFFYFKNLSCQRIT-LHKNLFFSFVCNSIITIISLSAVANNqalvatNPVICK-ISQFI 233
Cdd:cd15443    4 LTYISIVGCSISAAASLLTILLHFFSRKQPKDSTTrIHMNLLGSLFLLNGSFLLSPPLATSQ------STWLCRaAAALL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 234 HLYLMGCnYFWMLCEGIYLHTLIV-VAVFAEKQHLMWYYLLGWGFP-LIPACIHAVARSLY-----------YNDN-CWI 299
Cdd:cd15443   78 HYSLLCC-LTWMAIEGFHLYLLLVkVYNIYIRRYVLKLCVLGWGLPaLIVLLVLIFKREAYgphtiptgtgyQNASmCWI 156

                 ....
gi 148225847 300 SSET 303
Cdd:cd15443  157 TSSK 160
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
158-293 5.98e-03

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: 38.27  E-value: 5.98e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148225847 158 YLTIIGHGLSIASLLISL-GIFFYFKNLSCQR---ITLHKNLFFSfvcnsiITIISLSAVANNQALVATNPVICKIS-QF 232
Cdd:cd15995    3 YLTILTYVGCIISALASVfTIAFYLCSRRKPRdytIYVHMNLLLA------IFLLDTSFLISEPLALTGSEAACRAGgMF 76
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 148225847 233 IHLYLMGCnYFWMLCEGIYLHTLiVVAVFAE--KQHLMWYYLLGWGFPLIPACIHAVARSLYY 293
Cdd:cd15995   77 LHFSLLAC-LTWMGIEGYNLYRL-VVEVFNTyvPHFLLKLCAVGWGLPIFLVTLIFLVDQDNY 137
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.16
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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