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Conserved domains on  [gi|296317300|ref|NP_001171764|]
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adhesion G-protein coupled receptor G2 isoform 7 precursor [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
587-856 2.40e-174

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


:

Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 507.83  E-value: 2.40e-174
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 587 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYK-MQGLCISVAVFLHY 665
Cdd:cd15444    1 MLILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKdIVGLCISVAVFLHY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 666 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSPDDFCWINNN 745
Cdd:cd15444   81 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYGLGSYGKSPNGSTDDFCWINNN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 746 AVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYL 825
Cdd:cd15444  161 IVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAWGPVNLAFMYL 240
                        250       260       270
                 ....*....|....*....|....*....|.
gi 296317300 826 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15444  241 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 271
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
529-579 2.92e-14

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.


:

Pssm-ID: 197639  Cd Length: 49  Bit Score: 67.80  E-value: 2.92e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 296317300   529 TVRCVFWDlgrnGGRGGWSDNGCSVKDRRLNETICTCSHLTSFGVLLDLSR 579
Cdd:smart00303   2 NPICVFWD----ESSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPP 48
PHA03247 super family cl33720
large tegument protein UL36; Provisional
209-382 2.50e-06

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 51.86  E-value: 2.50e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  209 ADHPRGPPFSSSQSIPVVPRAtVLSQVPKATSFAEPPDYSPVTHNVPSPIGEIQPLSPQPSAPIASSPAIDMPPQSETiS 288
Cdd:PHA03247 2667 ARRLGRAAQASSPPQRPRRRA-ARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPA-V 2744
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  289 SPMPQTHVSGTPPPVKASFSSPTVSAPANVNTTSAPPVQTDIVNTSSISDLENQVLQMEKALSLGSLEPNLAGEMINQVS 368
Cdd:PHA03247 2745 PAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASP 2824
                         170
                  ....*....|....
gi 296317300  369 RLLHSPPDMLAPLA 382
Cdd:PHA03247 2825 AGPLPPPTSAQPTA 2838
 
Name Accession Description Interval E-value
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
587-856 2.40e-174

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


Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 507.83  E-value: 2.40e-174
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 587 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYK-MQGLCISVAVFLHY 665
Cdd:cd15444    1 MLILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKdIVGLCISVAVFLHY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 666 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSPDDFCWINNN 745
Cdd:cd15444   81 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYGLGSYGKSPNGSTDDFCWINNN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 746 AVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYL 825
Cdd:cd15444  161 IVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAWGPVNLAFMYL 240
                        250       260       270
                 ....*....|....*....|....*....|.
gi 296317300 826 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15444  241 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 271
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
587-837 4.58e-67

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 224.85  E-value: 4.58e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  587 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDyPSKILIQLCAALLLLNLVFLLDSWIALYKMQG------LCISVA 660
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCT-RNYIHLNLFASFILRALLFLVGDAVLFNKQDLdhcswvGCKVVA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  661 VFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVTIILTISPDNYGlgsygkfpngsPDDFC 740
Cdd:pfam00002  80 VFLHYFFLANFFWMLVEGLYLYTLLVEVFFSE-RKYFWWYLLIGWGVPALVVGIWAGVDPKGYG-----------EDDGC 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  741 WINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSI-QDLRSIAGLTFLLGITWGFAFFAWGPVN 819
Cdd:pfam00002 148 WLSNENGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYrRLAKSTLLLLPLLGITWVFGLFAFNPEN 227
                         250       260
                  ....*....|....*....|.
gi 296317300  820 ---VTFMYLFAIFNTLQGFFI 837
Cdd:pfam00002 228 tlrVVFLYLFLILNSFQGFFV 248
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
529-579 2.92e-14

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.


Pssm-ID: 197639  Cd Length: 49  Bit Score: 67.80  E-value: 2.92e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 296317300   529 TVRCVFWDlgrnGGRGGWSDNGCSVKDRRLNETICTCSHLTSFGVLLDLSR 579
Cdd:smart00303   2 NPICVFWD----ESSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPP 48
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
530-574 9.95e-14

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.


Pssm-ID: 460350  Cd Length: 44  Bit Score: 66.18  E-value: 9.95e-14
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 296317300  530 VRCVFWDLGrNGGRGGWSDNGCSVKDRRLNETICTCSHLTSFGVL 574
Cdd:pfam01825   1 PQCVFWDFT-NSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
PHA03247 PHA03247
large tegument protein UL36; Provisional
209-382 2.50e-06

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 51.86  E-value: 2.50e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  209 ADHPRGPPFSSSQSIPVVPRAtVLSQVPKATSFAEPPDYSPVTHNVPSPIGEIQPLSPQPSAPIASSPAIDMPPQSETiS 288
Cdd:PHA03247 2667 ARRLGRAAQASSPPQRPRRRA-ARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPA-V 2744
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  289 SPMPQTHVSGTPPPVKASFSSPTVSAPANVNTTSAPPVQTDIVNTSSISDLENQVLQMEKALSLGSLEPNLAGEMINQVS 368
Cdd:PHA03247 2745 PAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASP 2824
                         170
                  ....*....|....
gi 296317300  369 RLLHSPPDMLAPLA 382
Cdd:PHA03247 2825 AGPLPPPTSAQPTA 2838
Gag_spuma pfam03276
Spumavirus gag protein;
211-400 1.05e-05

Spumavirus gag protein;


Pssm-ID: 460872 [Multi-domain]  Cd Length: 614  Bit Score: 49.36  E-value: 1.05e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  211 HPRGPPFSSSQSIPVvPRATVL-SQVPKATSFAEPPDYSPVTHNVPsPIGEIQPLSP----------QPSAPIASSPAID 279
Cdd:pfam03276 205 HLPAIPGIHARAPPG-NIARSLgDDIMPSLGDAGMPQPRFAFHPGN-PFAEAEGHPFaeaegerprdIPRAPRIDAPSAP 282
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  280 MPPQSETISSPMPQTHVSGTPPPVKASFSSPTVSAPANV---NTTSAP------PVQTDIVNTSSISDLENQVLQMEKAL 350
Cdd:pfam03276 283 AIPAIQPIAPPMIPPIGAPIPIPHGASIPGEHIRNPREEpirLGREAPaidgrfAPAIDDLFCRIINALLCGIIGALLGG 362
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 296317300  351 SLG-SLEPNLAGEMINQVSRL-LHSPPDMLAPLAQRLLK-VVDDIGLQLNFSN 400
Cdd:pfam03276 363 GDCiSLDPADAILFDRAVAQLfIHQLGNVLKGIADNEGKaIADQEGMALAGQL 415
 
Name Accession Description Interval E-value
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
587-856 2.40e-174

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


Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 507.83  E-value: 2.40e-174
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 587 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYK-MQGLCISVAVFLHY 665
Cdd:cd15444    1 MLILTFITYIGCGLSAIFLSVTLVTYIAFEKIRRDYPSKILIQLCVALLLLNLVFLLDSWIALYKdIVGLCISVAVFLHY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 666 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSPDDFCWINNN 745
Cdd:cd15444   81 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYGLGSYGKSPNGSTDDFCWINNN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 746 AVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYL 825
Cdd:cd15444  161 IVFYITVVGYFCVIFLLNISMFIVVLVQLCRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITWGFAFFAWGPVNLAFMYL 240
                        250       260       270
                 ....*....|....*....|....*....|.
gi 296317300 826 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15444  241 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 271
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
587-854 1.16e-143

orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Group VIII adhesion GPCRs include orphan GPCRs such as GPR56, GPR64, GPR97, GPR112, GPR114, and GPR126. GPR56 is involved in the regulation of oligodendrocyte development and myelination in the central nervous system via coupling to G(12/13) proteins, which leads to the activation of RhoA GTPase. GPR126, on the other hand, is required for Schwann cells, but not oligodendrocyte myelination in the peripheral nervous system. Gpr64 is mainly expressed in the epididymis of male reproductive tract, and targeted deletion of GPR64 causes sperm stasis and efferent duct blockage due to abnormal fluid reabsorption, resulting in male infertility. GPR64 is also over-expressed in Ewing's sarcoma (ES), as well as upregulated in other carcinomas from kidney, prostate or lung, and promotes invasiveness and metastasis in ES via the upregulation of placental growth factor (PGF) and matrix metalloproteinase (MMP) 1. GPR97 is identified as a lymphatic adhesion receptor that is specifically expressed in lymphatic endothelium, but not in blood vascular endothelium, and is shown to regulate migration of lymphatic endothelial cells via the small GTPases RhoA and cdc42. GPR112 is specifically expressed in normal enterochromatin cells and gastrointestinal neuroendocrine carcinoma cells, but its biological function is unknown. GPR114 is mainly found in granulocytes (polymorphonuclear leukocytes), and GPR114-transfected cells induced an increase in cAMP levels via coupling to G(s) protein. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320386 [Multi-domain]  Cd Length: 267  Bit Score: 428.37  E-value: 1.16e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 587 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYF 666
Cdd:cd15258    1 LHILTFISYVGCGISAIFLAITILTYIAFRKLRRDYPSKIHMNLCAALLLLNLAFLLSSWIASFGSDGLCIAVAVALHYF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 667 LLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSPDDFCWINNNA 746
Cdd:cd15258   81 LLACLTWMGLEAFHLYLLLVKVFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPITIPNGEGFQNDSFCWIRDPV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 747 VFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLgAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLF 826
Cdd:cd15258  161 VFYITVVGYFGLTFLFNMVMLATVLVQICRLREKAQA-TPRKRALHDLLTLLGLTFLLGLTWGLAFFAWGPFNLPFLYLF 239
                        250       260
                 ....*....|....*....|....*...
gi 296317300 827 AIFNTLQGFFIFIFYCVAKENVRKQWRR 854
Cdd:cd15258  240 AIFNSLQGFFIFIWYCSMKENVRKQWRA 267
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
590-856 1.15e-141

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


Pssm-ID: 320663  Cd Length: 269  Bit Score: 423.30  E-value: 1.15e-141
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 590 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYFLLV 669
Cdd:cd15997    4 LTLITYLGCGISSIFLGITLVTYLAFEKLRRDYPSKILINLCTALLMLNLVFLLNSWLSSFNNYGLCITVAAFLHYFLLA 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 670 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSpDDFCWINNNAVFY 749
Cdd:cd15997   84 SFTWMGLEAVHMYFALVKVFNIYIPNYILKFCIAGWGIPAVVVALVLAINKDFYGNELSSDSLHPS-TPFCWIQDDVVFY 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 750 ITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLFAIF 829
Cdd:cd15997  163 ISVVAYFCLIFLCNISMFITVLIQIRSMKAKKPSRNWKQGFLHDLKSVASLTFLLGLTWGFAFFAWGPVRIFFLYLFSIC 242
                        250       260
                 ....*....|....*....|....*..
gi 296317300 830 NTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15997  243 NTLQGFFIFVFHCLMKENVRKQWRIHL 269
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
590-856 5.99e-125

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


Pssm-ID: 320662  Cd Length: 271  Bit Score: 380.00  E-value: 5.99e-125
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 590 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYFLLV 669
Cdd:cd15996    4 LTFITYIGCGISAIFSAATLLTYIAFEKLRRDYPSKILMNLSTALLFLNLVFLLDGWIASFEIDELCITVAVLLHFFLLA 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 670 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSP-DDFCWINNNAVF 748
Cdd:cd15996   84 TFTWMGLEAIHMYIALVKVFNTYIRRYILKFCIIGWGLPALIVSIVLASTNDNYGYGYYGKDKDGQGgDEFCWIKNPVVF 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 749 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLFAI 828
Cdd:cd15996  164 YVTCAAYFGIMFLMNVAMFIVVMVQICGRNGKRSNRTLREEILRNLRSVVSLTFLLGMTWGFAFFAWGPVNLAFMYLFTI 243
                        250       260
                 ....*....|....*....|....*...
gi 296317300 829 FNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15996  244 FNSLQGLFIFVFHCALKENVQKQWRRHL 271
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
589-852 4.23e-90

adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G protein-coupled receptors; The B2 subfamily of class B GPCRs consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320168 [Multi-domain]  Cd Length: 253  Bit Score: 287.55  E-value: 4.23e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 589 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKMqgLCISVAVFLHYFLL 668
Cdd:cd15040    3 ALSIITYIGCGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLLFLFGINSTDNPV--LCTAVAALLHYFLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 669 VSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGsygkfpngspDDFCWINNNAVF 748
Cdd:cd15040   81 ASFMWMLVEALLLYLRLVKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNS----------SGYCWLSNGNGL 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 749 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQdLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLFAI 828
Cdd:cd15040  151 YYAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQ-LRAAVSLFFLLGLTWIFGILAIFGARVVFQYLFAI 229
                        250       260
                 ....*....|....*....|....
gi 296317300 829 FNTLQGFFIFIFYCVAKENVRKQW 852
Cdd:cd15040  230 FNSLQGFFIFIFHCLRNKEVRKAW 253
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
589-852 2.68e-73

class B family of seven-transmembrane G protein-coupled receptors; The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.


Pssm-ID: 410627 [Multi-domain]  Cd Length: 260  Bit Score: 242.50  E-value: 2.68e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 589 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRdYPSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYFLL 668
Cdd:cd13952    3 ALSIITYIGCSLSLVGLLLTIITYLLFPKLRN-LRGKILINLCLSLLLAQLLFLIGQLLTSSDRPVLCKALAILLHYFLL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 669 VSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKfpngspDDFCWINNNAVF 748
Cdd:cd13952   82 ASFFWMLVEAFDLYRTFVKVFGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYG------GEYCWLSNGNAL 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 749 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAW-GPVNVTFMYLFA 827
Cdd:cd13952  156 LWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSDRKQLRAYLKLFPLMGLTWIFGILAPfVGGSLVFWYLFD 235
                        250       260
                 ....*....|....*....|....*
gi 296317300 828 IFNTLQGFFIFIFYCVAKENVRKQW 852
Cdd:cd13952  236 ILNSLQGFFIFLIFCLKNKEVRRLL 260
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
587-837 4.58e-67

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 224.85  E-value: 4.58e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  587 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDyPSKILIQLCAALLLLNLVFLLDSWIALYKMQG------LCISVA 660
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCT-RNYIHLNLFASFILRALLFLVGDAVLFNKQDLdhcswvGCKVVA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  661 VFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVTIILTISPDNYGlgsygkfpngsPDDFC 740
Cdd:pfam00002  80 VFLHYFFLANFFWMLVEGLYLYTLLVEVFFSE-RKYFWWYLLIGWGVPALVVGIWAGVDPKGYG-----------EDDGC 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  741 WINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSI-QDLRSIAGLTFLLGITWGFAFFAWGPVN 819
Cdd:pfam00002 148 WLSNENGLWWIIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYrRLAKSTLLLLPLLGITWVFGLFAFNPEN 227
                         250       260
                  ....*....|....*....|.
gi 296317300  820 ---VTFMYLFAIFNTLQGFFI 837
Cdd:pfam00002 228 tlrVVFLYLFLILNSFQGFFV 248
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
590-843 1.14e-58

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


Pssm-ID: 320558 [Multi-domain]  Cd Length: 277  Bit Score: 202.72  E-value: 1.14e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 590 LTFITYIGCGLSSIFLSVTLVTYIA----FEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHY 665
Cdd:cd15442    4 LVTISSAGCGVSMVFLIFTIILYFFlrftYQKFKSEDAPKIHVNLSSSLLLLNLAFLLNSGVSSRAHPGLCKALGGVTHY 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 666 FLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIilTISPDNYGLGSYGKFPNGSPDDFCWINNN 745
Cdd:cd15442   84 FLLCCFTWMAIEAFHLYLLAIKVFNTYIHHYFAKLCLVGWGFPALVVTI--TGSINSYGAYTIMDMANRTTLHLCWINSK 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 746 A--VFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLrSIAGLTFLLGITWGFAFFAWGPVNVTFM 823
Cdd:cd15442  162 HltVHYITVCGYFGLTFLFNTVVLGLVAWKIFHLQSATAGKEKCQAWKGGL-TVLGLSCLLGVTWGLAFFTYGSMSVPTV 240
                        250       260
                 ....*....|....*....|
gi 296317300 824 YLFAIFNTLQGFFIFIFYCV 843
Cdd:cd15442  241 YIFALLNSLQGLFIFIWFVI 260
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
590-849 6.13e-57

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


Pssm-ID: 320559 [Multi-domain]  Cd Length: 268  Bit Score: 197.29  E-value: 6.13e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 590 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYFLLV 669
Cdd:cd15443    4 LTYISIVGCSISAAASLLTILLHFFSRKQPKDSTTRIHMNLLGSLFLLNGSFLLSPPLATSQSTWLCRAAAALLHYSLLC 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 670 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSPDDFCWINNNAVFY 749
Cdd:cd15443   84 CLTWMAIEGFHLYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFKREAYGPHTIPTGTGYQNASMCWITSSKVHY 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 750 ITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRktSIQDLRSIAGLTFLLGITWGFAFFAWGPVNVTFMYLFAIF 829
Cdd:cd15443  164 VLVLGYAGLTSLFNLVVLAWVVRMLRRLRSRKQELGER--ARRDWVTVLGLTCLLGTTWALAFFSFGVFLIPQLFLFTII 241
                        250       260
                 ....*....|....*....|
gi 296317300 830 NTLQGFFIFIFYCVAKENVR 849
Cdd:cd15443  242 NSLYGFFICLWYCTQRRRSD 261
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
589-856 3.12e-47

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


Pssm-ID: 320556 [Multi-domain]  Cd Length: 259  Bit Score: 169.37  E-value: 3.12e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 589 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDypsKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYFLL 668
Cdd:cd15440    3 ALTFITYIGCIISIVCLLLAFITFTCFRNLQCD---RNTIHKNLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 669 VSFTWMGLEAFHMYLALVKVFNTYIRKyILKFCIVGWGVPAVVVTIILTISPDNYGlgsygkfpngsPDDFCWINNNAVF 748
Cdd:cd15440   80 AAFSWMLLEGFQLYVMLVEVFEPEKSR-IKWYYLFGYGLPALIVAVSAGVDPTGYG-----------TEDHCWLSTENGF 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 749 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKK--KKQLGAQRKTSIQD-LRSIAGLTFLLGITWGFAFFAWGPVNVTFMYL 825
Cdd:cd15440  148 IWSFVGPVIVVLLANLVFLGMAIYVMCRHSSrsASKKDASKLKNIRGwLKGSIVLVVLLGLTWTFGLLFINQESIVMAYI 227
                        250       260       270
                 ....*....|....*....|....*....|.
gi 296317300 826 FAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15440  228 FTILNSLQGLFIFIFHCVLNEKVRKELRRWL 258
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
590-850 2.08e-44

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: 161.92  E-value: 2.08e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 590 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYFLLV 669
Cdd:cd15995    4 LTILTYVGCIISALASVFTIAFYLCSRRKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAACRAGGMFLHFSLLA 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 670 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPngSPDDF-----CWINN 744
Cdd:cd15995   84 CLTWMGIEGYNLYRLVVEVFNTYVPHFLLKLCAVGWGLPIFLVTLIFLVDQDNYGPIILAVHR--SPEKVtyatiCWITD 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 745 NAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQlgaqrktSIQDLRSIAGLTFLLGITWGFAFFAW--GPVNVTF 822
Cdd:cd15995  162 SLISNITNLGLFSLVFLFNMAMLATMVVEILRLRPRTH-------KWSHVLTLLGLSLVLGIPWALAFFSFasGTFQLVI 234
                        250       260
                 ....*....|....*....|....*...
gi 296317300 823 MYLFAIFNTLQGFFIFIFYCVAKENVRK 850
Cdd:cd15995  235 VYLFTIINSLQGFLIFLWYWSMVLQARG 262
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
588-852 1.16e-43

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


Pssm-ID: 320599 [Multi-domain]  Cd Length: 252  Bit Score: 159.03  E-value: 1.16e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 588 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYpSKILIQLCAALLLLNLVFLLDSWIALYKMqgLCISVAVFLHYFL 667
Cdd:cd15933    2 RALSIISYIGCGISIACLALTLIIFLVLRVLSSDR-FQIHKNLCVALLLAQILLLAGEWAEGNKV--ACKVVAILLHFFF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 668 LVSFTWMGLEAFHMYLALVKVFNTYIRKYIlkFCIVGWGVPAVVVTIILTISPDNYGLgsygkfpngspDDFCW--INNN 745
Cdd:cd15933   79 MAAFSWMLVEGLHLYLMIVKVFNYKSKMRY--YYFIGWGLPAIIVAISLAILFDDYGS-----------PNVCWlsLDDG 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 746 AVFYITVVgyfcVIFLLNVSMFIVVLV-----QLCRIKKKKQLG--AQRKTSIqdlRSIAGLTFLLGITWGFAFFAWGPV 818
Cdd:cd15933  146 LIWAFVGP----VIFIITVNTVILILVvkitvSLSTNDAKKSQGtlAQIKSTA---KASVVLLPILGLTWLFGVLVVNSQ 218
                        250       260       270
                 ....*....|....*....|....*....|....
gi 296317300 819 NVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQW 852
Cdd:cd15933  219 TIVFQYIFVILNSLQGLMIFLFHCVLNSEVRSAF 252
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
656-857 9.62e-41

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


Pssm-ID: 320557 [Multi-domain]  Cd Length: 254  Bit Score: 150.86  E-value: 9.62e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNtyIRKYILKFC-IVGWGVPAVVVTIILTISPDNYGlgsygkfpng 734
Cdd:cd15441   67 CKLIAILLHYFYLSAFSWLLVESLHLYRMLTEPRD--INHGHMRFYyLLGYGIPAIIVGLSVGLRPDGYG---------- 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 735 sPDDFCWINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQlgaqRKTSIQ-DLRSIAGLTFLLGITWGFAFF 813
Cdd:cd15441  135 -NPDFCWLSVNETLIWSFAGPIAFVIVITLIIFILALRASCTLKRHVL----EKASVRtDLRSSFLLLPLLGATWVFGLL 209
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 296317300 814 AwgpVN---VTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYLC 857
Cdd:cd15441  210 A---VNedsELLHYLFAGLNFLQGLFIFLFYCIFNKKVRRELKNALL 253
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
589-858 3.91e-38

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


Pssm-ID: 320555 [Multi-domain]  Cd Length: 263  Bit Score: 143.64  E-value: 3.91e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 589 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLdswIALYKMQGLCISVAVFLHYFLL 668
Cdd:cd15439    3 ALTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQLSLCLFLADLLFLVG---IDRTDNKVLCSIIAGFLHYLFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 669 VSFTWMGLEAFHMYLAL--VKVFN-TYIRKYILKF-CIVGWGVPAVVVTIILTISPDNYGLGSYgkfpngspddfCWINN 744
Cdd:cd15439   80 ACFAWMFLEAVHLFLTVrnLKVVNyFSSHRFKKRFmYPVGYGLPAVIVAISAAVNPQGYGTPKH-----------CWLSM 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 745 NAVFYITVVGYFCVIFLLNVSMFIVVLVQLcriKKK-----KQLGAQRKTSIQDLRSIAGLtFLLGITWGFAFFAWGPVN 819
Cdd:cd15439  149 EKGFIWSFLGPVCVIIVINLVLFCLTLWIL---REKlsslnAEVSTLKNTRLLTFKAIAQL-FILGCTWILGLFQVGPVA 224
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 296317300 820 VTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYLCC 858
Cdd:cd15439  225 TVMAYLFTITNSLQGVFIFLVHCLLNRQVREEYRRWITG 263
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
593-854 1.41e-37

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


Pssm-ID: 410632 [Multi-domain]  Cd Length: 270  Bit Score: 141.98  E-value: 1.41e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 593 ITYIGCGLSSIFLSVTLVTYIAFEKIRrDYPSKILIQLCAALLLLNLVFLLDSWIALYKmQGLCISVAVFLHYFLLVSFT 672
Cdd:cd15039    7 LTLIGLIISLVFLLLTLAVYALLPELR-NLHGKCLMCLVLSLFVAYLLLLIGQLLSSGD-STLCVALGILLHFFFLAAFF 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 673 WMGLEAFHMYLAL----VKVFNTYIRKYILKFCIVGWGVPAVVVTIILTIS---PDNYGLGSYGkfpngspDDFCWINNN 745
Cdd:cd15039   85 WLNVMSFDIWRTFrgkrSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDfspNTDSLRPGYG-------EGSCWISNP 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 746 AVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKK-KQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAW-GPVNVTFM 823
Cdd:cd15039  158 WALLLYFYGPVALLLLFNIILFILTAIRIRKVKKEtAKVQSRLRSDKQRFRLYLKLFVIMGVTWILEIISWfVGGSSVLW 237
                        250       260       270
                 ....*....|....*....|....*....|.
gi 296317300 824 YLFAIFNTLQGFFIFIFYcVAKENVRKQWRR 854
Cdd:cd15039  238 YIFDILNGLQGVFIFLIF-VCKRRVLRLLKK 267
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
588-856 1.20e-36

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


Pssm-ID: 320380 [Multi-domain]  Cd Length: 257  Bit Score: 139.18  E-value: 1.20e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 588 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRD----YPSKILIQLCAALLLLNLVFLLDSWIAlykmqglCISVAVFL 663
Cdd:cd15252    2 NILTRITQVGIIISLVCLAICIFTFWFFRGLQSDrttiHKNLCISLFLAELVFLIGINTTTNKIF-------CSVIAGLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 664 HYFLLVSFTWMGLEAFHMYLALVKVFNT--YIRKYilkFCIVGWGVPAVVVTIILTISPDNYGlgsygkfpngsPDDFCW 741
Cdd:cd15252   75 HYFFLAAFAWMFIEGIQLYLMLVEVFENegSRHKN---FYIFGYGSPAVIVGVSAALGYRYYG-----------TTKVCW 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 742 INNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQD-LRSIAGLTFLLGITWGFAFFAWGPVNV 820
Cdd:cd15252  141 LSTENYFIWSFIGPATLIILLNLIFLGVAIYKMFRHTAGLKPEVSCLENIRSwARGAIALLFLLGLTWIFGVLHINHASV 220
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 296317300 821 TFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15252  221 VMAYLFTVSNSLQGMFIFLFHCVLSRKVRKEYYKLF 256
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
656-857 2.77e-32

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


Pssm-ID: 320554 [Multi-domain]  Cd Length: 261  Bit Score: 126.42  E-value: 2.77e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYiLKFCIVGWGVPAVVVTIILTISPDNYGlgsygkfpngs 735
Cdd:cd15438   67 CAVVAGLLHYFFLAAFCWMSLEGVELYLMVVQVFNTQSLKK-RYLLLIGYGVPLVIVAISAAVNSKGYG----------- 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 736 PDDFCWINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCR--IKKKKQLGAQRKTSIQDLRSIAGLtFLLGITWGFAFF 813
Cdd:cd15438  135 TQRHCWLSLERGFLWSFLGPVCLIILVNAIIFVITVWKLAEkfSSINPDMEKLRKIRALTITAIAQL-CILGCTWIFGFF 213
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 296317300 814 AWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYLC 857
Cdd:cd15438  214 QFSDSTLVMSYLFTILNSLQGLFIFLLHCLLSKQVREEYSRWLC 257
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
589-850 1.09e-30

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


Pssm-ID: 320385 [Multi-domain]  Cd Length: 303  Bit Score: 123.06  E-value: 1.09e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 589 ALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKI-----------------------LIQLCAALLLLNLVFLLDS 645
Cdd:cd15257    3 TLDIISTIGCVLSIAGLVITIIFHLHTRKLRKSSVTWVllnlcsslllfniiftsgventnNDYEISTVPDRETNTVLLS 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 646 WIALYKMQGLCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTIS---PDN 722
Cdd:cd15257   83 EEYVEPDTDVCTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQASAIGWGIPAVVVAITLGATyrfPTS 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 723 YGLGSYGKfpngSPDDFCWIN--------NNAVFY--ITVVGyfcVIFLLNVSMFIVVLVQLCriKKKKQLGAQRKTSIQ 792
Cdd:cd15257  163 LPVFTRTY----RQEEFCWLAaldknfdiKKPLLWgfLLPVG---LILITNVILFIMTSQKVL--KKNNKKLTTKKRSYM 233
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 296317300 793 DLRSIA-GLTFLLGITWGFAFFAW---GPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRK 850
Cdd:cd15257  234 KKIYITvSVAVVFGITWILGYLMLvnnDLSKLVFSYIFCITNTTQGVQIFILYTWRTPEFRK 295
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
588-853 2.13e-30

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


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 121.19  E-value: 2.13e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 588 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIrrdypSKILIQLCAALLLLNLVFLLDSWIALYKMQGL-----CISVAVF 662
Cdd:cd15256    2 VALSSITYVGCSLSIFCLAITLVTFAVLSSV-----STIRNQRYHIHANLSFAVLVAQILLLISFRFEpgtlpCKIMAIL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 663 LHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGVPAVVVTIILTISPDNYGlgsygkfpngsPDDFCWI 742
Cdd:cd15256   77 LHFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGI-GWGSPLLICIISLTSALDSYG-----------ESDNCWL 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 743 N--NNAVFYITVVGYFcvIFLLNVSMFIVVLVQLCRIKKKkQLGAQRKTSIQDL--RSIAGLTFLLGITWGFAFFAWGPV 818
Cdd:cd15256  145 SleNGAIWAFVAPALF--VIVVNIGILIAVTRVISRISAD-NYKVHGDANAFKLtaKAVAVLLPILGSSWVFGVLAVNTH 221
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 296317300 819 NVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWR 853
Cdd:cd15256  222 ALVFQYMFAIFNSLQGFFIFLFHCLLNSEVRAAFK 256
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
656-856 8.87e-29

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


Pssm-ID: 320673 [Multi-domain]  Cd Length: 258  Bit Score: 116.17  E-value: 8.87e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYILKFCivGWGVPAVVVTIILTISPDNYGlgsygkfpng 734
Cdd:cd16007   67 CPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVEVFESeYSRKKYYYLC--GYCFPALVVGISAAIDYRSYG---------- 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 735 sPDDFCWINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQD--LRSIAgLTFLLGITWGFAF 812
Cdd:cd16007  135 -TEKACWLRVDNYFIWSFIGPVSFVIVVNLVFLMVTLHKMIRSSSVLKPDSSRLDNIKSwaLGAIT-LLFLLGLTWAFGL 212
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 296317300 813 FAWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd16007  213 LFINKESVVMAYLFTTFNAFQGMFIFIFHCALQKKVHKEYSKCL 256
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
655-856 1.11e-27

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


Pssm-ID: 320657 [Multi-domain]  Cd Length: 254  Bit Score: 113.02  E-value: 1.11e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 655 LCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT---YIRKYIlkfcIVGWGVPAVVVTIILTISPDNYGlgsygkf 731
Cdd:cd15991   66 VCTVVAILLHYFYMSTFAWMFVEGLHIYRMLTEVRNIntgHMRFYY----VVGWGIPAIITGLAVGLDPQGYG------- 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 732 pngSPDdFCWINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRikkKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFA 811
Cdd:cd15991  135 ---NPD-FCWLSVQDTLIWSFAGPIGIVVIINTVIFVLAAKASCG---RRQRYFEKSGVISMLRTAFLLLLLISATWLLG 207
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 296317300 812 FFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15991  208 LMAVNSDTLSFHYLFAIFSCLQGIFIFFFHCIFNKEVRKHLKNVL 252
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
588-856 4.30e-27

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


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 111.57  E-value: 4.30e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 588 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRD----YPSKILIQLCAALLLLNLVFLLDSWIAlykmqglCISVAVFL 663
Cdd:cd16005    2 LLLDVITWVGILLSLVCLLICIFTFCFFRGLQSDrntiHKNLCISLFVAELLFLIGINRTDQPIA-------CAVFAALL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 664 HYFLLVSFTWMGLEAFHMYLALVKVFNT--YIRKYilkFCIVGWGVPAVVVTIILTISPDNYGlgsygkfpngsPDDFCW 741
Cdd:cd16005   75 HFFFLAAFTWMFLEGVQLYIMLVEVFESehSRRKY---FYLVGYGMPALIVAVSAAVDYRSYG-----------TDKVCW 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 742 INNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKK--KKQLGAQRKTSIQDLRSIAgLTFLLGITWGFAFFAWGPVN 819
Cdd:cd16005  141 LRLDTYFIWSFIGPATLIIMLNVIFLGIALYKMFHHTAilKPESGCLDNIKSWVIGAIA-LLCLLGLTWAFGLMYINEST 219
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 296317300 820 VTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd16005  220 VIMAYLFTIFNSLQGMFIFIFHCVLQKKVRKEYGKCL 256
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
656-857 6.77e-27

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


Pssm-ID: 320597 [Multi-domain]  Cd Length: 262  Bit Score: 111.07  E-value: 6.77e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYILK---FCIVGWGVPAVVVTIILTISPDNYGLGSYgkf 731
Cdd:cd15931   67 CTVMAGLLHYLFLASFVWMLLEALQLHLLVRRLTKVqVIQRDGLPrplLCLIGYGVPFLIVGVSALVYSDGYGEAKM--- 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 732 pngspddfCWINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRI--KKKKQLGAQRKTSIQDLRSIAGLtFLLGITWG 809
Cdd:cd15931  144 --------CWLSQERGFNWSFLGPVIAIIGINWILFCATLWCLRQTlsNMNSDISQLKDTRLLTFKAVAQL-FILGCTWV 214
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 296317300 810 FAFFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYLC 857
Cdd:cd15931  215 LGLFQTNPVALVFQYLFTILNSLQGAFLFLVHCLLNKEVREEYIKWLT 262
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
656-856 1.29e-26

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


Pssm-ID: 320552 [Multi-domain]  Cd Length: 258  Bit Score: 109.88  E-value: 1.29e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYI--RKYilkFCIVGWGVPAVVVTIILTISPDNYGlgsygkfpn 733
Cdd:cd15436   67 CPIFAGLLHFFFLAAFCWLCLEGVQLYLLLVEVFESEYsrRKY---FYLCGYSFPALVVAVSAAIDYRSYG--------- 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 734 gsPDDFCWINNNAVFYITVVGYFCVIFLLNVsmfIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIA----GLTFLLGITWG 809
Cdd:cd15436  135 --TEKACWLRVDNYFIWSFIGPVTFVITLNL---VFLVITLHKMVSHSDLLKPDSSRLDNIKSWAlgaiALLFLLGLTWS 209
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 296317300 810 FAFFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15436  210 FGLMFINEESVVMAYLFTIFNAFQGVFIFIFHCALQKKVRKEYSKCL 256
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
588-854 1.65e-26

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


Pssm-ID: 320672 [Multi-domain]  Cd Length: 258  Bit Score: 109.62  E-value: 1.65e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 588 MALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLdswIALYKMQGLCISVAVFLHYFL 667
Cdd:cd16006    2 LLLTVITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIG---IDKTEYKIACPIFAGLLHFFF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 668 LVSFTWMGLEAFHMYLALVKVFNTYI--RKYilkFCIVGWGVPAVVVTIILTISPDNYGlgsygkfpngsPDDFCWINNN 745
Cdd:cd16006   79 LAAFAWMCLEGVQLYLMLVEVFESEYsrKKY---YYVAGYLFPATVVGVSAAIDYKSYG-----------TEKACWLRVD 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 746 AVFYITVVGYFCVIFLLNVsmfIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTF----LLGITWGFAFFAWGPVNVT 821
Cdd:cd16006  145 NYFIWSFIGPVTFIILLNL---IFLVITLCKMVKHSNTLKPDSSRLENIKSWVLGAFallcLLGLTWSFGLLFINEETIV 221
                        250       260       270
                 ....*....|....*....|....*....|...
gi 296317300 822 FMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRR 854
Cdd:cd16006  222 MAYLFTIFNAFQGMFIFIFHCALQKKVRKEYSK 254
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
590-854 6.21e-26

Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; member of the class B2 family of seven-transmembrane G protein-coupled receptors; ETL (EGF-TM7-latrophilin-related protein) belongs to Group I adhesion GPCRs, which also include latrophilins (also called lectomedins or latrotoxin receptors). All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. ETL, for instance, contains EGF-like repeats, which also present in other EGF-TM7 adhesion GPCRs, such as Cadherin EGF LAG seven-pass G-type receptors (CELSR1-3), EGF-like module receptors (EMR1-3), CD97, and Flamingo. ETL is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320553 [Multi-domain]  Cd Length: 258  Bit Score: 108.04  E-value: 6.21e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 590 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRdypSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYFLLV 669
Cdd:cd15437    4 LTRITQLGIIISLICLSMCIFTFWFFSEIQS---TRTTIHKNLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 670 SFTWMGLEAFHMYLALVKVFntYIRKYILK-FCIVGWGVPAVVVTIILTISPDNYGlgsygkfpngsPDDFCWINNNAVF 748
Cdd:cd15437   81 AFAWMCIEGIHLYLIVVGVI--YNKGFLHKnFYIFGYGSPAVVVGISAALGYKYYG-----------TTKVCWLSTENNF 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 749 YITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQlgaQRKTSIQDLRSIA----GLTFLLGITWGFAFFAWGPVNVTFMY 824
Cdd:cd15437  148 IWSFIGPACLIILVNLLAFGVIIYKVFRHTAMLK---PEVSCYENIRSCArgalALLFLLGATWIFGVLHVVYGSVVTAY 224
                        250       260       270
                 ....*....|....*....|....*....|
gi 296317300 825 LFAIFNTLQGFFIFIFYCVAKENVRKQWRR 854
Cdd:cd15437  225 LFTISNAFQGMFIFIFLCVLSRKIQEEYYR 254
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
653-853 1.32e-24

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


Pssm-ID: 320659 [Multi-domain]  Cd Length: 254  Bit Score: 104.15  E-value: 1.32e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 653 QGLCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGVPAVVVTIILTISPDNYGlgsygkfp 732
Cdd:cd15993   64 QFLCTVVAILLHYFFLSTFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAI-GWGVPAIITGLAVGLDPEGYG-------- 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 733 ngSPDdFCWINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKqlgAQRKTSIQDLRSIAGLTFLLGITWGFAF 812
Cdd:cd15993  135 --NPD-FCWISIHDKLVWSFAGPIVVVIVMNGVMFLLVARMSCSPGQKE---TKKTSVLMTLRSSFLLLLLISATWLFGL 208
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 296317300 813 FAWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWR 853
Cdd:cd15993  209 LAVNNSVLAFHYLHAILCCLQGLAVLLLFCVLNEEVQEAWK 249
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
589-849 7.65e-24

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


Pssm-ID: 320598 [Multi-domain]  Cd Length: 268  Bit Score: 102.39  E-value: 7.65e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 589 ALTFITYIGCGLSSIFLSVTLVTYIAFEK-IRRDYPSKILIQLCAALLLLNLVFllDSW--IALY-----KMQGLCISVA 660
Cdd:cd15932    3 ALDYITYVGLGISILSLVLCLIIEALVWKsVTKNKTSYMRHVCLVNIALSLLIA--DIWfiIGAAistppNPSPACTAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 661 VFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILK--FCiVGWGVPAV--VVTIILTiSPDNYGLGSygkfpngsp 736
Cdd:cd15932   81 FFIHFFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAiaFS-LGYGCPLIiaIITVAAT-APQGGYTRK--------- 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 737 dDFCWIN-NNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTS-IQDLRSIAGLTFLLGITWGFAFF- 813
Cdd:cd15932  150 -GVCWLNwDKTKALLAFVIPALAIVVVNFIILIVVIFKLLRPSVGERPSKDEKNAlVQIGKSVAILTPLLGLTWGFGLGt 228
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 296317300 814 AWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVR 849
Cdd:cd15932  229 MIDPKSLAFHIIFAILNSFQGFFILVFGTLLDSKVR 264
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
593-858 1.55e-22

orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group III adhesion GPCRs include orphan GPR123, GPR124, GPR125, and their closely related proteins. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 also interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Furthermore, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl.


Pssm-ID: 320387 [Multi-domain]  Cd Length: 260  Bit Score: 98.22  E-value: 1.55e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 593 ITYIGCGLSSIFLSVTLVTYIAFEKIRRdYPSKILIQLCAALLLLNLVFLLDSW-IALYKMQGLCISVAVFLHYFLLVSF 671
Cdd:cd15259    7 VVYAGAALCLLCLLATIITYIVFHRLIR-ISRKGRHMLVNLCLHLLLTCVVFVGgINRTANQLVCQAVGILLHYSTLCTL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 672 TWMGLEAFHMYLALVKVFNT--------YIRKYILKFCIVGWGVPAVVVTIILTISPDNYglgsygkfpngSPDDFCWIN 743
Cdd:cd15259   86 LWVGVTARNMYKQVTKTAKPpqdedqppRPPKPMLRFYLIGWGIPLIICGITAAVNLDNY-----------STYDYCWLA 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 744 NNA---VFYITVvgyfCVIFLLNVSMFIVVLVQLcrikkkkqlgAQRKTSIQD-LRSIAGLTFLLGITWGFAFFA---WG 816
Cdd:cd15259  155 WDPslgAFYGPA----ALIVLVNCIYFLRIYCQL----------KGAPVSFQSqLRGAVITLFLYVAMWACGALAvsqRY 220
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 296317300 817 PVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRylCC 858
Cdd:cd15259  221 FLDLVFSCLYGATCSSLGLFVLIHHCLSREDVRQSWRQ--CC 260
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
655-860 3.06e-22

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: 97.20  E-value: 3.06e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 655 LCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTY---IRKYILkfciVGWGVPAVVVTIILTISPDNYGlgsygkf 731
Cdd:cd15992   66 ACTVIAILLHFFYLCTFSWLFLEGLHIYRMLSEVRDINygpMRFYYL----IGWGVPAFITGLAVGLDPEGYG------- 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 732 pngSPDdFCWINnnavFYITVVGYFC--VIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWG 809
Cdd:cd15992  135 ---NPD-FCWLS----IYDTLIWSFAgpVAFAVSMNVFLYILSSRASCSAQQQSFEKKKGPVSGLRTAFTVLLLVSVTCL 206
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 296317300 810 FAFFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRryLCCGK 860
Cdd:cd15992  207 LALLSVNSDVILFHYLFAGFNCLQGPFIFLSHVVLLKEVRKALK--TLCGP 255
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
587-854 4.71e-22

The subfamily B1 of hormone receptors (secretin-like), member of the class B family seven-transmembrane G protein-coupled receptors; The B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of this subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. Moreover, the B1 subfamily receptors play key roles in hormone homeostasis and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzheimer###s and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression). Furthermore, the subfamilies B2 and B3 consist of receptors that are capable of interacting with epidermal growth factors (EGF) and the Drosophila melanogaster Methuselah gene product (Mth), respectively. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 341321 [Multi-domain]  Cd Length: 273  Bit Score: 96.91  E-value: 4.71e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 587 MMALTFITYIGCGLSSIFLSVTLVTYIAFEKIR--RDYPSK----------ILIQLCAALLLLNLVFLLDSWIALYKMQG 654
Cdd:cd15041    1 LLVVYYIYLVGYSLSLVALLPAIVIFLYFRSLRctRIRLHInlflsfilraVFWIIWDLLVVYDRLTSSGVETVLMQNPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 655 LCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFnTYIRKYILKFCIVGWGVPAVVVTIiltispdnYGLGSYGKfpng 734
Cdd:cd15041   81 GCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAF-FSEPSSLKLYYAIGWGLPLVIVVI--------WAIVRALL---- 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 735 sPDDFCWINNNA-----VFYITVVgyFC----VIFLLNVsmfIVVLVQlcrikkkkQLGAQRKTSIQDLRSIAGLTF--- 802
Cdd:cd15041  148 -SNESCWISYNNghyewILYGPNL--LAllvnLFFLINI---LRILLT--------KLRSHPNAEPSNYRKAVKATLili 213
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 296317300 803 -LLGITwgFAFFAWGP-----VNVTFMYLFAIFNTLQGFFIFIFYCVA----KENVRKQWRR 854
Cdd:cd15041  214 pLFGIQ--YLLTIYRPpdgseGELVYEYFNAILNSSQGFFVAVIYCFLngevQSELKRKWSR 273
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
596-853 2.12e-20

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: 91.93  E-value: 2.12e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 596 IGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKmqGLCISVAVFLHYFLLVSFTWMG 675
Cdd:cd15251   10 VGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILILVGQTQTLNK--GVCTMTAAFLHFFFLSSFCWVL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 676 LEAFHMYLALV-KVFNTYIRKyilKFCIVGWGVPAVVVTIILtispdnyglgSYGKFPNGSPDDFCWINNNAVFYITVVG 754
Cdd:cd15251   88 TEAWQSYMAVTgRMRTRLIRK---RFLCLGWGLPALVVAVSV----------GFTRTKGYGTSSYCWLSLEGGLLYAFVG 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 755 YFCVIFLLNVSMFIVVLVQLCrikkkkqlgaqRKTSIQDlRSIAGLTF------LLGITWGFAFFAWGPV-NVTFMYLFA 827
Cdd:cd15251  155 PAAAVVLVNMVIGILVFNKLV-----------SRDGISD-NAMASLWSscvvlpLLALTWMSAVLAMTDRrSVLFQILFA 222
                        250       260
                 ....*....|....*....|....*.
gi 296317300 828 IFNTLQGFFIFIFYCVAKENVRKQWR 853
Cdd:cd15251  223 VFDSLQGFVIVMVHCILRREVQDAVK 248
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
596-849 2.61e-19

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


Pssm-ID: 320654 [Multi-domain]  Cd Length: 291  Bit Score: 89.63  E-value: 2.61e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 596 IGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKmqGLCISVAVFLHYFLLVSFTWMG 675
Cdd:cd15988   10 IGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVGQSQTLSK--GVCTMTAAFLHFFFLSSFCWVL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 676 LEAFHMYLALV-KVFNTYIRKyilKFCIVGWGVPAVVVTIILTIS-PDNYGLGSYgkfpngspddfCWINNNAVFYITVV 753
Cdd:cd15988   88 TEAWQSYLAVIgRMRTRLVRK---RFLCLGWGLPALVVAVSVGFTrTKGYGTASY-----------CWLSLEGGLLYAFV 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 754 GYFCVIFLLNVSMFIVVLVQLCR------IKKKKQLGAQR--------------------------KTSIQDLRSIAGLT 801
Cdd:cd15988  154 GPAAVIVLVNMLIGIIVFNKLMSrdgisdKSKKQRAGSEAepcsslllkcskcgvvssaamssataSSAMASLWSSCVVL 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 296317300 802 FLLGITWGFAFFAWGP-VNVTFMYLFAIFNTLQGFFIFIFYCVAKENVR 849
Cdd:cd15988  234 PLLALTWMSAVLAMTDrRSILFQVLFAVFNSVQGFVIITVHCFLRREVQ 282
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
656-856 6.88e-19

insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Nilaparvata lugens (brown planthopper) and its closely related proteins from mollusks and annelid worms. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320388 [Multi-domain]  Cd Length: 267  Bit Score: 87.71  E-value: 6.88e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFntyIRKYILK--FCIVGWGVPAVVVTIiltispdnyglgsYGKFPN 733
Cdd:cd15260   75 CQALHVLLQYFMVCNYFWMFCEGLYLHTVLVVAF---ISEKSLMrwFIAIGWGVPLVITAI-------------YAGVRA 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 734 GSPDD--FCWINNNAVFYITVVGYFC-----VIFLLNVsmfIVVLVqlcriKKKKQLGAQRKTSI--QDLRSIAGLTFLL 804
Cdd:cd15260  139 SLPDDteRCWMEESSYQWILIVPVVLsllinLIFLINI---VRVLL-----TKLRATSPNPAPAGlrKAVRATLILIPLL 210
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 296317300 805 GITWGFAFF---AWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15260  211 GLQFLLIPFrpePGAPLETIYQYVSALLTSLQGLCVAVLFCFCNGEVIAAIKRKW 265
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
589-858 2.20e-18

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


Pssm-ID: 320381 [Multi-domain]  Cd Length: 271  Bit Score: 86.35  E-value: 2.20e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 589 ALTFITYIGCGLSSIFLSVTLVTY-IAFEKIRRDYPSKILIQLCAALLLLNLVFLL----DSWIALYKMQGLCISVAVFL 663
Cdd:cd15253    3 WLDFLSQVGLGASILALLLCLGIYrLVWRSVVRNKISYFRHMTLVNIAFSLLLADTcflgATFLSAGHESPLCLAAAFLC 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 664 HYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCI-VGWGVPAVVVTIILTISpdnYGLGSYGKfpngspDDFCWI 742
Cdd:cd15253   83 HFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVtLGYLCPLLIAAATVAYY---YPKRQYLH------EGACWL 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 743 NNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIK-KKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAFFAW-GPVNV 820
Cdd:cd15253  154 NGESGAIYAFSIPVLAIVLVNLLVLFVVLMKLMRPSvSEGPPPEERKALLSIFKALLVLTPVFGLTWGLGVATLtGESSQ 233
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 296317300 821 TFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYLCC 858
Cdd:cd15253  234 VSHYGFAILNAFQGVFILLFGCLMDKKVREALLKRLCK 271
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
590-850 9.31e-18

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


Pssm-ID: 320382 [Multi-domain]  Cd Length: 275  Bit Score: 84.47  E-value: 9.31e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 590 LTFITYIGCGLSSIFLSVTLV----TYIAFEKIRRDYPSKILIQLCAALLLLNlvfllDSWIAL--------YKMQG-LC 656
Cdd:cd15254    4 LDYITYIGLSISILSLAICIVieslVWKSVTKNRTSYMRHVCILNIAVSLLIA-----DIWFIVvaaiqdqnYAVNGnVC 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 657 ISVAVFLHYFLLVSFTWM---GLEAFHMYLALVKVFNTYIRKYIlKFCIvGWGVPAV--VVTIILTISPDNYglgsygkf 731
Cdd:cd15254   79 VAATFFIHFFYLCVFFWMlalGLMLFYRLVFILHDTSKTIQKAV-AFCL-GYGCPLIisVITIAVTLPRDSY-------- 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 732 pngSPDDFCWIN-NNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIK-KKKQLGAQRKTSIQDLRSIAGLTFLLGITWG 809
Cdd:cd15254  149 ---TRKKVCWLNwEDSKALLAFVIPALIIVAVNSIITVVVIVKILRPSiGEKPSKQERSSLFQIIKSIGVLTPLLGLTWG 225
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 296317300 810 FAFFAWGP-VNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRK 850
Cdd:cd15254  226 FGLATVIKgSSIVFHILFTLLNAFQGLFILVFGTLWDKKVQE 267
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
590-854 2.86e-17

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR144 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR133. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the Gs protein, leading to activation of adenylyl cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320383 [Multi-domain]  Cd Length: 263  Bit Score: 82.97  E-value: 2.86e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 590 LTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDYpSKILIQLCAALLLLNLVFLLDSWIAlyKMQGLCISVAVFLHYFLLV 669
Cdd:cd15255    4 LRTLSFIGCGVSLCALIVTFILFLAVGVPKSER-TTVHKNLIFALAAAEFLLMFSEWAK--GNQVACWAVTALLHLFFLA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 670 SFTWMGLEAFHMYLALVKVFNTYIRKYILKFcIVGWGVPAVVVTIILTISPDNYglgsygkfpngSPDDFCWINNNAVFY 749
Cdd:cd15255   81 AFSWMLVEGLLLWSKVVAVNMSEDRRMKFYY-VTGWGLPVVIVAVTLATSFNKY-----------VADQHCWLNVQTDII 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 750 ITVVGyfCVIFLLNVSMFI---VVLVQLCRIKKKKQL-----GAQRKTSIQ---DLRSIAGLTFLLGITWGFAFFAwgPV 818
Cdd:cd15255  149 WAFVG--PVLFVLTVNTFVlfrVVMVTVSSARRRAKMltpssDLEKQIGIQiwaTAKPVLVLLPVLGLTWLCGVLV--HL 224
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 296317300 819 NVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRR 854
Cdd:cd15255  225 SDVWAYVFITLNSFQGLYIFLVYAIYNSEVRNAIQR 260
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
591-849 7.84e-17

insect diuretic hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors that specifically bind to insect diuretic hormones found in Manduca sexta (moth) and Acheta domesticus (the house cricket), among others. Insect diuretic hormone and their GPCRs play critical roles in the regulation of water and ion balance. Thus they are attractive targets for developing new insecticides. Activation of the diuretic hormone receptors stimulate adenylate cyclase, thereby increasing cAMP levels in Malpighian tube. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of Gs family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx.


Pssm-ID: 320391 [Multi-domain]  Cd Length: 272  Bit Score: 81.65  E-value: 7.84e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 591 TFITYIGCGLSSIFLSVTLVTYIAFEKIR--RDypsKILIQLCAALLLLNLvflldSWIALYKMQ-------GLCISVAV 661
Cdd:cd15263    5 TTIYFIGYSLSLVALSLALWIFLYFKDLRclRN---TIHTNLMFTYILADL-----TWILTLTLQvsigedqKSCIILVV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 662 FLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSPDDFCW 741
Cdd:cd15263   77 LLHYFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYAFI-GWGIPAVVIVIWAIVKALAPTAPNTALDPNGLLKHCPW 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 742 INNNAV--FYITVVgyfCVIFLLNV---SMFIVVLVQLCRIKKKKQLGAQRKTSiqdlRSIAGLTFLLGITwgFAFFAWG 816
Cdd:cd15263  156 MAEHIVdwIFQGPA---ILVLAVNLvflVRIMWVLITKLRSANTVETQQYRKAA----KALLVLIPLLGIT--YILVIAG 226
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 296317300 817 P----VNVTFMYLFAIFNTLQGFFIFIFYCVAKENVR 849
Cdd:cd15263  227 PtegiAANIFEYVRAVLLSTQGFTVALFYCFLNTEVR 263
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
596-850 6.28e-16

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: 78.88  E-value: 6.28e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 596 IGCGLSSIFLSVTLVTYIAFEKIRRDYPSKILIQLCAALLLLNLVFLLDSWIALYKMqgLCISVAVFLHYFLLVSFTWMG 675
Cdd:cd15990   13 VGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALILIGQTQTRNKV--VCTLVAAFLHFFFLSSFCWVL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 676 LEAFHMYLALV-KVFNTYIRKyilKFCIVGWGVPAVVVTIILTISPDNyglgSYGKFpngspdDFCWINNNAVFYITVVG 754
Cdd:cd15990   91 TEAWQSYMAVTgRLRNRIIRK---RFLCLGWGLPALVVAISVGFTKAK----GYGTV------NYCWLSLEGGLLYAFVG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 755 YFCVIFLLNVSMFIVVLVQLCR------IKKKKQLGAQRKTSIQDLRsiagltfLLGITWGFAFFAWGP-VNVTFMYLFA 827
Cdd:cd15990  158 PAAAVVLVNMVIGILVFNKLVSkdgitdKKLKERAGASLWSSCVVLP-------LLALTWMSAVLAITDrRSALFQILFA 230
                        250       260
                 ....*....|....*....|...
gi 296317300 828 IFNTLQGFFIFIFYCVAKENVRK 850
Cdd:cd15990  231 VFDSLEGFVIVMVHCILRREVQD 253
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
655-858 2.27e-15

G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR123 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, and also includes orphan receptors GPR124 and GPR125. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells, yet its biological function remains to be determined. 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: 320666 [Multi-domain]  Cd Length: 275  Bit Score: 77.69  E-value: 2.27e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 655 LCISVAVFLHYFLLVSFTWMGLEAFHMYLALVK----VFNT----YIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLG 726
Cdd:cd16000   69 ICQAVGIVLHYSTLSTMLWIGVTARNIYKQVTKkphlCQDTdqppYPKQPLLRFYLVSGGVPFIICGITAATNINNYGTE 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 727 SYGKfpngspdDFCWIN---NNAVFYitvvGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFL 803
Cdd:cd16000  149 DEDT-------PYCWMAwepSLGAFY----GPVAFIVLVTCIYFLCTYVQLRRHPERKYELKNEHSFKAQLRAAAFTLFL 217
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 296317300 804 LGITWGFAFFA--WGP-VNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWrrYLCC 858
Cdd:cd16000  218 FTATWAFGALAvsQGHfLDMIFSCLYGAFCVTLGLFILIHHCAKRDDVWHCW--WSCC 273
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
529-579 2.92e-14

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.


Pssm-ID: 197639  Cd Length: 49  Bit Score: 67.80  E-value: 2.92e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 296317300   529 TVRCVFWDlgrnGGRGGWSDNGCSVKDRRLNETICTCSHLTSFGVLLDLSR 579
Cdd:smart00303   2 NPICVFWD----ESSGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDVPP 48
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
530-574 9.95e-14

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.


Pssm-ID: 460350  Cd Length: 44  Bit Score: 66.18  E-value: 9.95e-14
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 296317300  530 VRCVFWDLGrNGGRGGWSDNGCSVKDRRLNETICTCSHLTSFGVL 574
Cdd:pfam01825   1 PQCVFWDFT-NSTTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
656-853 3.42e-13

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


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 70.77  E-value: 3.42e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVTI--ILTISPDNYGlgsygkfpn 733
Cdd:cd15987   77 CKAVMVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPE-RRYFYWYTIIGWGTPTICVTVwaVLRLHFDDTG--------- 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 734 gspddfCW-INNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKT-SIQDLRSIAGLTFLLGITwgFA 811
Cdd:cd15987  147 ------CWdMNDNTALWWVIKGPVVGSIMINFVLFIGIIIILVQKLQSPDIGGNESSiYLRLARSTLLLIPLFGIH--YT 218
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 296317300 812 FFAWGPVNVTF--MYLFAI-FNTLQGFFIFIFYCV----AKENVRKQWR 853
Cdd:cd15987  219 VFAFSPENVSKreRLVFELgLGSFQGFVVAVLYCFlngeVQSEIKRKWR 267
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
653-853 5.74e-13

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


Pssm-ID: 320655 [Multi-domain]  Cd Length: 293  Bit Score: 70.48  E-value: 5.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 653 QGLCISVAVFLHYFLLVSFTWMGLEAFHMYLALV-KVFNTYIRKyilKFCIVGWGVPAVVVTIILTISPDNyGLGSygkf 731
Cdd:cd15989   67 KGICTMTTAFLHFFFLASFCWVLTEAWQSYMAVTgKIRTRLIRK---RFLCLGWGLPALVVAISMGFTKAK-GYGT---- 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 732 pngspDDFCWINNNAVFYITVVGYFCVIFLLNVSMFIVVLVQL-------------------------------CRIKKK 780
Cdd:cd15989  139 -----PHYCWLSLEGGLLYAFVGPAAAVVLVNMVIGILVFNKLvsrdgildkklkhragqmsephsgltlkcakCGVVST 213
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 296317300 781 KQLGAQRKT-SIQDLRSIAGLTFLLGITWGFAFFAW-GPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWR 853
Cdd:cd15989  214 TALSATTASnAMASLWSSCVVLPLLALTWMSAVLAMtDKRSILFQILFAVFDSLQGFVIVMVHCILRREVQDAFR 288
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
656-854 2.30e-12

secretin receptor-like group of hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group represents G protein-coupled receptors for structurally similar peptide hormones that include secretin, growth-hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide (VIP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Secretin, a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion. Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptors, which are expressed in the brain, pancreas, stomach, kidney, and liver. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. All B1 subfamily GPCRs are able to increase intracellular cAMP levels by coupling to adenylate cyclase via a stimulatory Gs protein. However, depending on its cellular location, some members of subfamily B1 are also capable of coupling to additional G proteins such as G(i/o) and/or G(q) proteins, thereby leading to activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320596 [Multi-domain]  Cd Length: 268  Bit Score: 68.23  E-value: 2.30e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFnTYIRKYILKFCIVGWGVPAVVVT--IILTISPDNYGlgsygkfpn 733
Cdd:cd15930   77 CKASMVFFQYCVMANFFWLLVEGLYLHTLLVISF-FSERRYFWWYVLIGWGAPTVFVTvwIVARLYFEDTG--------- 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 734 gspddfCW-INNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDL-RSIAGLTFLLGITWG-F 810
Cdd:cd15930  147 ------CWdINDESPYWWIIKGPILISILVNFVLFINIIRILLQKLRSPDIGGNESSQYKRLaRSTLLLIPLFGIHYIvF 220
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 296317300 811 AFFawgPVNVTF---MYLFAIFNTLQGFFIFIFYCVAKENV----RKQWRR 854
Cdd:cd15930  221 AFF---PENISLgirLYFELCLGSFQGFVVAVLYCFLNGEVqaeiKRKWRS 268
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
654-854 3.06e-12

corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320561 [Multi-domain]  Cd Length: 265  Bit Score: 68.04  E-value: 3.06e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 654 GLCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYIlkFCIVGWGVP--AVVVTIILTISPDNyglgsygk 730
Cdd:cd15445   71 VWCRLVTAAYNYFHVTNFFWMFGEGCYLHTAIVLTYSTdKLRKWM--FICIGWCIPfpIIVAWAIGKLYYDN-------- 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 731 fpngspdDFCWINNNAVFYITVV--GYFCVIFLLNvsmfIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAG---LTFLLG 805
Cdd:cd15445  141 -------EKCWFGKRAGVYTDYIyqGPMILVLLIN----FIFLFNIVRILMTKLRASTTSETIQYRKAVKAtlvLLPLLG 209
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 296317300 806 ITWGFAFFAWGPVNVT---FMYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRR 854
Cdd:cd15445  210 ITYMLFFVNPGEDEISrivFIYFNSFLESFQGFFVSVFYCFlnseVRSAVRKRWHR 265
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
593-854 3.64e-12

corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320392 [Multi-domain]  Cd Length: 265  Bit Score: 67.83  E-value: 3.64e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 593 ITYIGCGLSSIFLSVTLVTYIAFEKIR---RDYPSKILIQLCAALLLLNLVFLLDSWIALYKMQGLC-ISVAVFlHYFLL 668
Cdd:cd15264    7 IYYLGFSISLVALAVALIIFLYFRSLRclrNNIHCNLIVTFILRNVTWFIMQNTLTEIHHQSNQWVCrLIVTVY-NYFQV 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 669 VSFTWMGLEAFHMYLALVKVFNT-YIRKYIlkFCIVGWGVPAVVVtIILTISPdNYGLGSYGKFPNGSPDDFCWINNNAV 747
Cdd:cd15264   86 TNFFWMFVEGLYLHTMIVWAYSAdKIRFWY--YIVIGWCIPCPFV-LAWAIVK-LLYENEHCWLPKSENSYYDYIYQGPI 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 748 FYITVVGyfcVIFLLNVsmfIVVLVQLCRIKKKKQLGAQRKTsiqdLRSIAGLTFLLGITWGFAFFAWGP---VNVTFMY 824
Cdd:cd15264  162 LLVLLIN---FIFLFNI---VWVLITKLRASNTLETIQYRKA----VKATLVLLPLLGITYMLFFINPGDdktSRLVFIY 231
                        250       260       270
                 ....*....|....*....|....*....|
gi 296317300 825 LFAIFNTLQGFFIFIFYCVAKENVRKQWRR 854
Cdd:cd15264  232 FNTFLQSFQGLFVAVFYCFLNGEVRSAIRK 261
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
655-849 6.87e-12

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


Pssm-ID: 320660 [Multi-domain]  Cd Length: 267  Bit Score: 66.79  E-value: 6.87e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 655 LCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIR-KYILKFCIVGWGVPAVVVTIILTIS-PDNYGLGSygkfp 732
Cdd:cd15994   75 LCVAATFFLHFFYLSLFFWMLTKALLILYGILLVFFKITKsVFIATAFSIGYGCPLVIAVLTVAITePKKGYLRP----- 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 733 ngspdDFCWIN--NNAVFYITVVGYFcVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGF 810
Cdd:cd15994  150 -----EACWLNwdETKALLAFIIPAL-SIVVVNLIVVGVVVVKTQRSSIGESCKQDVSNIIRISKNVAILTPLLGLTWGF 223
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 296317300 811 AFFAW-GPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVR 849
Cdd:cd15994  224 GLATIiDSRSLPFHIIFALLNAFQGFFILLFGTILDRKIR 263
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
655-857 1.80e-11

growth-hormone-releasing hormone receptor type 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor type 2 (GHRHR2) is found in non-mammalian vertebrates such as chicken and frog. It is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide, and mammalian growth hormone-releasing hormone. These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Mammalian GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. Mammalian GHRH is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. GHRHR is found in mammals as well as zebrafish and chicken, whereas the GHRHR type 2, an ortholog of the GHRHR, has only been identified in ray-finned fish, chicken and Xenopus. Xenopus laevis GHRHR2 has been shown to interact with both endogenous GHRH and PACAP-related peptide (PRP).


Pssm-ID: 320399 [Multi-domain]  Cd Length: 267  Bit Score: 65.52  E-value: 1.80e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 655 LCISVAVFLHYFLLVSFTWMGLEAfhMYLALVKVFN-TYIRKYILKFCIVGWGVPAVVVTI-ILT-ISPDNYGlgsygkf 731
Cdd:cd15271   76 ACKAAVTFFQFCVLANFFWLLVEG--MYLQTLLLLTfTSDRKYFWWYILIGWGAPSVTVTVwVLTrLQYDNRG------- 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 732 pngspddfCWINNNAVFYITVVGYFCVIFLLNVSMFIVV---LVQlcRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITW 808
Cdd:cd15271  147 --------CWDDLESRIWWIIKTPILLSVFVNFLIFINViriLVQ--KLKSPDVGGNDTSHYMRLAKSTLLLIPLFGVHY 216
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 296317300 809 G-FAFFawgPVNVTF---MYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYLC 857
Cdd:cd15271  217 VvFAFF---PEHVGVearLYFELVLGSFQGFIVALLYCFLNGEVQAEIKKRLG 266
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
656-854 2.51e-11

corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 65.37  E-value: 2.51e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYIlkFCIVGWGVPAVVVtIILTISPDNYglgsygkfpng 734
Cdd:cd15446   72 CRCITTIYNYFVVTNFFWMFVEGCYLHTAIVMTYSTdKLRKWV--FLFIGWCIPCPII-VAWAIGKLYY----------- 137
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 735 sPDDFCWINNNAVFYITVVGYFCVIFLLNVSMfiVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAG---LTFLLGITWGFA 811
Cdd:cd15446  138 -ENEQCWFGKEPGKYIDYIYQGPVILVLLINF--VFLFNIVRILMTKLRASTTSETIQYRKAVKAtlvLLPLLGITYMLF 214
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 296317300 812 FFAWGPVNVT---FMYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRR 854
Cdd:cd15446  215 FVNPGEDDISqivFIYFNSFLQSFQGFFVSVFYCFlngeVRSAARKRWHR 264
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
651-854 7.50e-11

parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone (PTH) receptor family has three subtypes: PTH1R, PTH2R and PTH3R. PTH1R is expressed in bone and kidney and is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to G(s)-protein that in turn activates adenylate cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple intracellular signaling pathways. PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. PTH3R is found in chicken and fish, but it is absent in mammals. The PTH receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320650 [Multi-domain]  Cd Length: 290  Bit Score: 64.20  E-value: 7.50e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 651 KMQGLCISVAV-FLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVTIILTISPDnyglgsyg 729
Cdd:cd15984   89 KAQFVGCKVAVtFFLYFLATNYYWILVEGLYLHSLIFMAFFSE-KKYLWGFTLFGWGLPAVFVTIWASVRAT-------- 159
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 730 kfpngSPDDFCW-INNNAVFYITVVGYFCVIfLLNVSMFIVVLVQLCriKKKKQLGAQRKTSIQDLRSIAGLTFLLGITW 808
Cdd:cd15984  160 -----LADTGCWdLSAGNLKWIIQVPILAAI-VVNFILFINIVRVLA--TKLRETNAGRCDTRQQYRKLLKSTLVLMPLF 231
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 296317300 809 G-----FAFFAWGPVNVTF----MYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRR 854
Cdd:cd15984  232 GvhyivFMAMPYTEVSGILwqvqMHYEMLFNSFQGFFVAIIYCFcngeVQAEIKKSWSR 290
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
645-854 9.32e-10

The pigment dispersing factor receptor, member of the class B seven-transmembrane G protein-coupled receptors; The pigment dispersing factor receptor (PDFR) is a G protein-coupled receptor that binds the circadian clock neuropeptide PDF, a functional ortholog of the mammalian vasoactive intestinal peptide (VIP), on the pacemaker neurons. The PDFR is implicated in regulating flight circuit development and in modulating acute flight In Drosophila melanogaster. The PDFR activation stimulates adenylate cyclase, thereby increasing cAMP levels in many different pacemakers, and the receptor signaling has been shown to regulate behavioral circadian rhythms and geotaxis in Drosophila. The PDFR belongs to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. . These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. They play key roles in hormone homeostasis in mammals and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzheimer###s and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression).


Pssm-ID: 320389 [Multi-domain]  Cd Length: 282  Bit Score: 60.84  E-value: 9.32e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 645 SWIALYKMQGLCISVAVFLHYFLLVSFTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGVPAVVVTIILTISPDNY 723
Cdd:cd15261   77 EGRTINSTPILCEGFYVLLEYAKTVMFMWMFIEGLYLHnIIVVSVFSG--KPNYLFYYILGWGIPIVHTSAWAIVTLIKM 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 724 GLGSygkfpngspddfCWINNN--AVFYITVVGYFCVI-----FLLNVsmfIVVLVQLCRIKKKKQLGAQRKTsiqdLRS 796
Cdd:cd15261  155 KVNR------------CWFGYYltPYYWILEGPRLAVIlinlfFLLNI---IRVLVSKLRESHSREIEQVRKA----VKA 215
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 296317300 797 IAGLTFLLGIT--------------WGFAFFAWGpvnVTFMYLFaifntlQGFFIFIFYCVAKENVR----KQWRR 854
Cdd:cd15261  216 AIVLLPLLGITnilqmipppltsviVGFAVWSYS---THFLTSF------QGFFVALIYCFLNGEVKnvlkKFWRR 282
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
656-854 1.02e-09

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


Pssm-ID: 320397 [Multi-domain]  Cd Length: 268  Bit Score: 60.64  E-value: 1.02e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVTI--ILTISPDNYGlgsygkfpn 733
Cdd:cd15269   77 CKAAMVFFQYCIMANFFWLLVEGLYLHTLLAVSFFSE-RKYFWWYILIGWGAPSVFITAwsVARIYFEDVG--------- 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 734 gspddfCW--INNNAVFYITVVGYFCVIfLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDL-RSIAGLTFLLGITwgF 810
Cdd:cd15269  147 ------CWdtIIESLLWWIIKTPILVSI-LVNFILFICIIRILVQKLHSPDIGRNESSQYSRLaKSTLLLIPLFGIH--Y 217
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 296317300 811 AFFAWGPVNVTF---MYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRR 854
Cdd:cd15269  218 IMFAFFPDNFKAevkLVFELILGSFQGFVVAVLYCFlngeVQAELKRKWRR 268
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
656-854 3.33e-09

glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon-like peptide-2 receptor (GLP2R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor (GCGR) and GLP1R. GLP2R is activated by glucagon-like peptide 2, which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. GLP2R belongs to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320394 [Multi-domain]  Cd Length: 280  Bit Score: 58.99  E-value: 3.33e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVT--IILTISPDNYGlgsygkfpn 733
Cdd:cd15266   87 CRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSE-RRLLKKYMLIGWGTPVLFVVpwGVAKILLENTG--------- 156
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 734 gspddfCW-INNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLgAQRKTSIQDLRSIAGLTFLLGI------ 806
Cdd:cd15266  157 ------CWgRNENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQM-RFTDYKYRLARSTLVLIPLLGIhevvfs 229
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 296317300 807 ------TWGFAFFAWGPVNVTfmylfaiFNTLQGFFIFIFYCVA----KENVRKQWRR 854
Cdd:cd15266  230 fitdeqVEGFSRHIRLFIQLT-------LSSFQGFLVAVLYCFAngevKAELKKRWQL 280
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
654-854 7.81e-09

parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone 2 receptor (PTH2R), one of the three subtypes of PTH receptor family, is found in mammals and fish, but not in chicken or frog. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39) but not by PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs. These results suggest that TIP-39 is a natural ligand for PTH2R. Conversely, PTH1R is activated by PTH and PTHrP, but not by TIP-39. The PTH family receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320648 [Multi-domain]  Cd Length: 289  Bit Score: 58.02  E-value: 7.81e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 654 GLCISVAVFLhYFLLVSFTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGVPAVVVTIILTISpdnyGLGSYGKFP 732
Cdd:cd15982   94 GCKIAVVMFI-YFLATNYYWILVEGLYLHsLIFVAFFSD--TKYLWGFTLIGWGFPAVFVAAWAVVR----ATLADARCW 166
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 733 NGSPDDFCWINNNAVfyITVVGYFCVIFLLNVSMFIVvlvqlcrikKKKQLGAQRKTSIQDLRSIAGLTFLLGITWGFAF 812
Cdd:cd15982  167 ELSAGDIKWIYQAPI--LAAIGLNFILFLNTVRVLAT---------KIWETNAVGYDTRKQYRKLAKSTLVLVLVFGVHY 235
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 296317300 813 FAWGPVNVTF--------MYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRR 854
Cdd:cd15982  236 IVFVCLPHTFtglgweirMHCELFFNSFQGFFVSIIYCYcngeVQTEIKKTWTR 289
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
647-856 8.46e-09

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


Pssm-ID: 320401 [Multi-domain]  Cd Length: 285  Bit Score: 57.77  E-value: 8.46e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 647 IALYKMQGLCISVAVFLHYFLLVSFTWMGLEAFHMY-LALVKVF--NTYIRKYIlkfcIVGWGVPAVVVT--IILTISPD 721
Cdd:cd15273   82 IANIGSNWVCKAITSLWQYFIIANYSWILMEGLYLHnLIFLALFsdENNIILYI----LLGWGLPLIFVVpwIVARILFE 157
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 722 NyglgsygkfpngspdDFCWI-NNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLcrIKKKKQLGAQRKTSIQDL-RSIAG 799
Cdd:cd15273  158 N---------------SLCWTtNSNLLNFLIIRIPIMISVLINFILFLNIVRVL--LVKLRSSVNEDSRRYKKWaKSTLV 220
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296317300 800 LTFLLGITW----GFAFFAWGPVNVTFMYLF--AIFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15273  221 LVPLFGVHYtiflILSYLDDTNEAVELIWLFcdQLFASFQGFFVALLYCFLNGEVRAEIQRKW 283
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
656-854 1.15e-07

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


Pssm-ID: 341342 [Multi-domain]  Cd Length: 279  Bit Score: 54.57  E-value: 1.15e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVkvFNTYIRKYILK-FCIVGWGVPAVVVTIiltispdnyglgsYGKFPNG 734
Cdd:cd15268   86 CRLVFLLMQYCVAANYYWLLVEGVYLYTLLA--FSVFSEQRIFRlYLSIGWGVPLLFVIP-------------WGIVKYL 150
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 735 SPDDFCWINNNAVFYITVVgYFCVIFLLNVSMFIVVLVqLCRIKKKKQLGAQRKTSIQDLRSIAGLTF--LLG---ITWG 809
Cdd:cd15268  151 YEDEGCWTRNSNMNYWLII-RLPILFAIGVNFLIFIRV-ICIVVSKLKANLMCKTDIKCRLAKSTLTLipLLGtheVIFA 228
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 296317300 810 FAFFAWGPVNVTFMYLFA--IFNTLQGFFIFIFYCVAKENV----RKQWRR 854
Cdd:cd15268  229 FVMDEHARGTLRFVKLFTelSFTSFQGLMVAILYCFVNNEVqmefRKSWER 279
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
647-858 3.13e-07

G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR124 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, which also includes orphan GPR123 and GPR125. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Moreover, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. 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: 320664 [Multi-domain]  Cd Length: 268  Bit Score: 53.04  E-value: 3.13e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 647 IALYKMQGLCISVAVFLHYFLLVSFTWMGLEAFHMYLALV---------KVFNTYIRKyILKFCIVGWGVPAVVVTIILT 717
Cdd:cd15998   61 ITLTNYQMVCQAVGITLHYSSLSTLLWMGVKARVLHKELTwrapppqegDPALPTPRP-MLRFYLIAGGIPLIICGITAA 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 718 ISPDNYglgsygkfPNGSPddFCWI---NNNAVFYITVVgyfcVIFLLNVSMFIVVLVQL-CRIKKKKQLGAQRktsiQD 793
Cdd:cd15998  140 VNIHNY--------RDHSP--YCWLvwrPSLGAFYIPVA----LILLVTWIYFLCAGLHLrGPSADGDSVYSPG----VQ 201
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 296317300 794 LRSIAGLTFLLGITWGFAFFA----WGPvNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRylCC 858
Cdd:cd15998  202 LGALVTTHFLYLAMWACGALAvsqrWLP-RVVCSCLYGVAASALGLFVFTHHCARRRDVRASWRA--CC 267
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
664-854 9.29e-07

invertebrate parathyroid hormone-related receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes parathyroid hormone (PTH)-related receptors found in invertebrates such as mollusks and annelid worms. The PTH family receptors are members of the B1 subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. The parathyroid hormone type 1 receptor (PTH1R) is found in all vertebrate species and is activated by two polypeptide ligands: parathyroid hormone (PTH), an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to G(s)- protein that in turn activates adenylyl cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple signaling pathways.


Pssm-ID: 320400 [Multi-domain]  Cd Length: 285  Bit Score: 51.62  E-value: 9.29e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 664 HYFLLVSFTWMGLEAFHMY-LALVKVFNtyIRKYILKFCIVGWG------VPAVVVTIILTispdnyglgsygkfpngsp 736
Cdd:cd15272   98 NYILGANYMWIFVEGLYLHmLIFVAVFS--ENSRVKWYILLGWLspllfvLPWVFVRATLE------------------- 156
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 737 DDFCW-INNNAVFYITVVGYFCVIFLLNVSMFI-VVLVQLCRIKKkkqlGAQRKTSIQDLRSIAGLTFLLGITWG--FAF 812
Cdd:cd15272  157 DTLCWnTNTNKGYFWIIRGPIVISIAINFLFFInIVRVLFTKLKA----SNTQESRPFRYRKLAKSTLVLIPLFGvhYMV 232
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 296317300 813 FAWGPVNVTF-------MYLFAIFNTLQGFFIFIFYC-----VAKEnVRKQWRR 854
Cdd:cd15272  233 FVVLPDSMSSdeaelvwLYFEMFFNSFQGFIVALLFCflngeVQSE-IKKKWQR 285
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
656-854 9.47e-07

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


Pssm-ID: 320393 [Multi-domain]  Cd Length: 289  Bit Score: 51.61  E-value: 9.47e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGVPAVVVTI--ILTISPDNYGLGSYgkfp 732
Cdd:cd15265   95 CKVAVTLFLYFLATNYYWILVEGLYLHsLIFMAFFSD--KKYLWGFTLIGWGFPAVFVIPwaSVRATLADTRCWDL---- 168
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 733 ngSPDDFCWINNNAVFYITVVGYfcvIFLLNVsmfIVVLVQlcrikKKKQLGAQRKTSIQDLRSIAGLTFLLGITWG--F 810
Cdd:cd15265  169 --SAGNYKWIYQVPILAAIVVNF---ILFLNI---VRVLAT-----KLRETNAGRCDTRQQYRKLAKSTLVLIPLFGvhY 235
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 296317300 811 AFFAWGPVNVTF------MYLFAIFNTLQGFFIFIFYC-----VAKEnVRKQWRR 854
Cdd:cd15265  236 IVFMGMPYTEVGllwqirMHYELFFNSFQGFFVAIIYCfcngeVQAE-IKKRWER 289
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
651-854 9.51e-07

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


Pssm-ID: 320649 [Multi-domain]  Cd Length: 285  Bit Score: 51.46  E-value: 9.51e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 651 KMQGLCISVAVFLhYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVTIILTISPDnyglgsygk 730
Cdd:cd15983   86 QWVGCKVTVTLFL-YFLATNHYWILVEGLYLHSLIFMAFLSD-KNYLWALTIIGWGLPAVFVSVWASVRVS--------- 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 731 fpngSPDDFCWI----NNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIqdLRSIAGLTFLLGI 806
Cdd:cd15983  155 ----LADTQCWDlsagNLKWIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKLDPRQQYRKL--LKSTLVLMPLFGV 228
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 296317300 807 TWgFAFFAWGPVNVTF------MYLFAIFNTLQGFFIFIFYCV----AKENVRKQWRR 854
Cdd:cd15983  229 HY-VLFMAMPYTDVTGllwqiqMHYEMLFNSSQGFFVAFIYCFcngeVQAEIKKAWLR 285
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
655-854 2.28e-06

growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor (GHRHR) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide. These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. GHRH is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. GHRHR is found in mammals as well as zebrafish and chicken, whereas the GHRHR type 2, an ortholog of the GHRHR, has only been identified in ray-finned fish, chicken and Xenopus. Xenopus laevis GHRHR2 has been shown to interact with both endogenous GHRH and PACAP-related peptide (PRP).


Pssm-ID: 320398 [Multi-domain]  Cd Length: 268  Bit Score: 50.18  E-value: 2.28e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 655 LCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFnTYIRKYILKFCIVGWGVPavVVTIILTISPDNYglgsygkfpng 734
Cdd:cd15270   76 LCKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSF-PRGKRYFWWLVLLGWGLP--TLCTGTWILCKLY----------- 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 735 SPDDFCW-INNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDL-RSIAGLTFLLGITWGFAF 812
Cdd:cd15270  142 FEDTECWdINNDSPYWWIIKGPIVISVGVNFLLFLNIIRILLKKLDPRQINFNNSAQYRRLsKSTLLLIPLFGTHYIIFN 221
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 296317300 813 FAWGPVNVTF-MYLFAIFNTLQGFFIFIFYCVAKENVRKQWRR 854
Cdd:cd15270  222 FLPDYAGLGIrLYLELCLGSFQGFIVAVLYCFLNQEVQTEISR 264
PHA03247 PHA03247
large tegument protein UL36; Provisional
209-382 2.50e-06

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 51.86  E-value: 2.50e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  209 ADHPRGPPFSSSQSIPVVPRAtVLSQVPKATSFAEPPDYSPVTHNVPSPIGEIQPLSPQPSAPIASSPAIDMPPQSETiS 288
Cdd:PHA03247 2667 ARRLGRAAQASSPPQRPRRRA-ARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPA-V 2744
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  289 SPMPQTHVSGTPPPVKASFSSPTVSAPANVNTTSAPPVQTDIVNTSSISDLENQVLQMEKALSLGSLEPNLAGEMINQVS 368
Cdd:PHA03247 2745 PAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASP 2824
                         170
                  ....*....|....
gi 296317300  369 RLLHSPPDMLAPLA 382
Cdd:PHA03247 2825 AGPLPPPTSAQPTA 2838
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
656-854 3.57e-06

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


Pssm-ID: 320403 [Multi-domain]  Cd Length: 271  Bit Score: 49.74  E-value: 3.57e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTyIRKYILKFCIVGWGVPAVVVTiiltispdNYGLGSYgkfpnGS 735
Cdd:cd15275   77 CKVAMVFSNYCIMANYSWLLVEGLYLHSLLSISFFS-ERKHLWWYIALGWGSPLIFII--------SWAIARY-----LH 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 736 PDDFCW-INNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLcrIKKKKQLGAQRKTSIQdLRSIAGLTFLLGITWG----- 809
Cdd:cd15275  143 ENEGCWdTRRNAWIWWIIRGPVILSIFVNFILFLNILRIL--MRKLRAPDMRGNEFSQ-YKRLAKSTLLLIPLFGlhyil 219
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 296317300 810 FAFFAWGPVNVTF-MYLFA--IFNTLQGFFIFIFYCV----AKENVRKQWRR 854
Cdd:cd15275  220 FAFFPEDVSSGTMeIWLFFelALGSFQGFVVAVLYCFlngeVQLEIQRKWRR 271
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
644-856 5.82e-06

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


Pssm-ID: 341353 [Multi-domain]  Cd Length: 279  Bit Score: 48.97  E-value: 5.82e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 644 DSWIALYKMQGL--CISVAVFLHYFLLVSFTWMGLEAFHMYLALvkVFNTYIRKYILK-FCIVGWGVPAVVVTiiltisP 720
Cdd:cd15929   72 DLWSTLLSNQASlgCRVAQVLMQYCVAANYYWLLVEGLYLHTLL--VLAVFSERSIFRlYLLLGWGAPVLFVV------P 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 721 dnYGLGSYGKfpngsPDDFCW-INNNAVFYITVVGYFCVIFLLNVSMFIVVLvQLCRIKKKKQLGAQRKTSIQDLRSIAG 799
Cdd:cd15929  144 --WGIVKYLY-----ENTGCWtRNDNMAYWWIIRLPILLAILINFFIFVRIL-KILVSKLRANQMCKTDYKFRLAKSTLT 215
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 296317300 800 LTFLLGITWG-FAFF----AWGpvNVTFMYLFA--IFNTLQGFFIFIFYCVAKENVRKQWRRYL 856
Cdd:cd15929  216 LIPLLGVHEVvFAFVtdeqARG--TLRFIKLFFelFLSSFQGLLVAVLYCFANKEVQSELRKKW 277
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
659-855 8.92e-06

calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors for calcitonin (CT) and calcitonin gene-related peptides (CGRPs). Calcitonin, a 32-amino acid peptide hormone, is involved in calcium metabolism in many mammalian species and acts to reduce blood calcium levels and directly inhibits bone resorption by acting on osteoclast. Thus, CT acts as an antagonist to parathyroid hormone and is commonly used in the treatment of bone disorders. The CT receptor is predominantly found in osteoclasts, kidney, and brain, and is primarily coupled to stimulatory G(s) protein, which leads to activation of adenylate cyclase, thereby increasing cAMP production. CGRP, a member of the calcitonin family of peptides, is a potent vasodilator and may contribute to migraine. It is expressed in the peripheral and central nervous system and exists in two forms in humans (alpha-CGRP and beta-CGRP). CGRP meditates its physiological effects through calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), a single transmembrane domain protein. Thus, the CRLR/RAMP1 complex serves as a functional CGRP receptor. On the other hand, the CRLR/RAMP2 and CRLR/RAMP3 complexes function as adrenomedullin-specific receptors. The CT and CGRP receptors belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide.


Pssm-ID: 341343 [Multi-domain]  Cd Length: 274  Bit Score: 48.62  E-value: 8.92e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 659 VAVFLHYFLLVS-FTWMGLEAFHMY-LALVKVFNTyiRKYILKFCIVGWGVPAVVVTIILTISPDNYglgsygkfpngsp 736
Cdd:cd15274   77 ILHFIHQYMMGCnYFWMLCEGIYLHtLIVVAVFAE--KQRLMWYYLLGWGFPLIPTTIHAITRAVYY------------- 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 737 DDFCWINNNAVFYITVVGYFCVIFLLNVsMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTFLLGITwgFAFFAWG 816
Cdd:cd15274  142 NDNCWLSSETHLLYIIHGPIMAALVVNF-FFLLNIVRVLVTKLRETHEAESHMYLKAVKATLILVPLLGIQ--FVLFPWR 218
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 296317300 817 P----VNVTFMYLFAIFNTLQGFFIFIFYCVAKENV----RKQWRRY 855
Cdd:cd15274  219 PsgkiLGKIYDYVMHSLIHFQGFFVATIFCFCNGEVqatlKRQWNQY 265
Gag_spuma pfam03276
Spumavirus gag protein;
211-400 1.05e-05

Spumavirus gag protein;


Pssm-ID: 460872 [Multi-domain]  Cd Length: 614  Bit Score: 49.36  E-value: 1.05e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  211 HPRGPPFSSSQSIPVvPRATVL-SQVPKATSFAEPPDYSPVTHNVPsPIGEIQPLSP----------QPSAPIASSPAID 279
Cdd:pfam03276 205 HLPAIPGIHARAPPG-NIARSLgDDIMPSLGDAGMPQPRFAFHPGN-PFAEAEGHPFaeaegerprdIPRAPRIDAPSAP 282
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  280 MPPQSETISSPMPQTHVSGTPPPVKASFSSPTVSAPANV---NTTSAP------PVQTDIVNTSSISDLENQVLQMEKAL 350
Cdd:pfam03276 283 AIPAIQPIAPPMIPPIGAPIPIPHGASIPGEHIRNPREEpirLGREAPaidgrfAPAIDDLFCRIINALLCGIIGALLGG 362
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 296317300  351 SLG-SLEPNLAGEMINQVSRL-LHSPPDMLAPLAQRLLK-VVDDIGLQLNFSN 400
Cdd:pfam03276 363 GDCiSLDPADAILFDRAVAQLfIHQLGNVLKGIADNEGKaIADQEGMALAGQL 415
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
215-384 1.14e-05

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 49.38  E-value: 1.14e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  215 PPFSSSQSIPVVPRATVLSQVPKATSfAEPPDYSPVTHNVPSPIGEIQPLSPQPSAPIASspAIDMPPQSETISSPMPQT 294
Cdd:pfam03154 171 PPVLQAQSGAASPPSPPPPGTTQAAT-AGPTPSAPSVPPQGSPATSQPPNQTQSTAAPHT--LIQQTPTLHPQRLPSPHP 247
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  295 HVSGTPPPVKASFSSPTVSAPANVNTTSAP---PVQTdivNTSSISD-LENQVLQMEKALSLGSLEPNLAGEMINQVSRL 370
Cdd:pfam03154 248 PLQPMTQPPPPSQVSPQPLPQPSLHGQMPPmphSLQT---GPSHMQHpVPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQR 324
                         170
                  ....*....|....
gi 296317300  371 LHSPPDMLAPLAQR 384
Cdd:pfam03154 325 IHTPPSQSQLQSQQ 338
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
656-853 1.66e-05

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


Pssm-ID: 320651 [Multi-domain]  Cd Length: 280  Bit Score: 47.62  E-value: 1.66e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYILKFCIvGWGVPAVVVTIILTIspdnyglgsygKFPNGS 735
Cdd:cd15985   87 CRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYL-GWGTPVLFVVPWMLA-----------KYLKEN 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 736 PDdfCW-INNNAVFYITVVGYFCVIFLLNVSMFIVVL-VQLCRIKKKKQLGAQRKTSIQdlRSIAGLTFLLGITWGFAFF 813
Cdd:cd15985  155 KE--CWaLNENMAYWWIIRIPILLASLINLLIFMRILkVILSKLRANQKGYADYKLRLA--KATLTLIPLFGIHEVVFIF 230
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 296317300 814 AWGPVNVTFMYLFAIF-----NTLQGFFIFIFYCVAKENVR----KQWR 853
Cdd:cd15985  231 ATDEQTTGILRYIKVFftlflNSFQGFLVAVLYCFANKEVKsellKKWR 279
PHA03247 PHA03247
large tegument protein UL36; Provisional
212-327 2.73e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.40  E-value: 2.73e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  212 PRGPPfssSQSIPVVPRATVLSQVPKATSFAEPPDYSPVTHNVPSPigeiqplspQPSAPIASSPAIDMPPqsETISSPM 291
Cdd:PHA03247 2772 PAAPA---AGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAP---------AAALPPAASPAGPLPP--PTSAQPT 2837
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 296317300  292 PQTHVSGTPPPVKASFSS-----------PTVSAPANVNTTSAPPVQ 327
Cdd:PHA03247 2838 APPPPPGPPPPSLPLGGSvapggdvrrrpPSRSPAAKPAAPARPPVR 2884
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
655-857 3.52e-05

G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR125 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, which also includes orphan receptors GPR123 and GPR124. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl. 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: 320665  Cd Length: 312  Bit Score: 46.78  E-value: 3.52e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 655 LCISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIR--------KYILKFCIVGWGVPAVVVTIILTISPDNyglg 726
Cdd:cd15999   69 VCQAVGIILHYSTLATVLWVGVTARNIYKQVTRKAKRCQDpdepppppRPMLRFYLIGGGIPIIVCGITAAANIKN---- 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 727 sYGKFPNGSpddFCWIN---NNAVFYitvvGYFCVIFLLNVSMFIVVLVQLCRIKKKK-------------------QLG 784
Cdd:cd15999  145 -YGSRPNAP---YCWMAwepSLGAFY----GPAGFIIFVNCMYFLSIFIQLKRHPERKyelkepteeqqrlaasehgELN 216
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 785 AQRKTSIQDLRSI------------------AGLT-FLLGITWGFAFFA---WGPVNVTFMYLFAIFNTLQGFFIFIFYC 842
Cdd:cd15999  217 HQDSGSSSASCSLvstsalenehsfqaqllgASLAlFLYVALWIFGALAvslYYPMDLVFSCLFGATCLSLGAFLVVHHC 296
                        250
                 ....*....|....*
gi 296317300 843 VAKENVRKQWRRYLC 857
Cdd:cd15999  297 VNREDVRRAWIATCC 311
PRK14948 PRK14948
DNA polymerase III subunit gamma/tau;
255-453 5.81e-05

DNA polymerase III subunit gamma/tau;


Pssm-ID: 237862 [Multi-domain]  Cd Length: 620  Bit Score: 46.88  E-value: 5.81e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 255 PSPIGEIQPLSPQPSAPIASSPAIDMPPQSETISSPMPQTHVSGTPPPVKAsfssPTVSAPANVNTTSAPPVQTDIVNTS 334
Cdd:PRK14948 361 PSAFISEIANASAPANPTPAPNPSPPPAPIQPSAPKTKQAATTPSPPPAKA----SPPIPVPAEPTEPSPTPPANAANAP 436
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 335 SISDLEnQVLQmekaLSLGSLEPNLAGEMINQVSRLLHSPPDM----LAP------------LAQRLLKVVDDiGLQLNF 398
Cdd:PRK14948 437 PSLNLE-ELWQ----QILAKLELPSTRMLLSQQAELVSLDSNRaviaVSPnwlgmvqsrkplLEQAFAKVLGR-SIKLNL 510
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 296317300 399 SNTTISLTSPSLALAVIRVNASSFNTTTFVAQDPANLQVSLETQAPENSIGTITL 453
Cdd:PRK14948 511 ESQSGSASNTAKTPPPPQKSPPPPAPTPPLPQPTATAPPPTPPPPPPTATQASSN 565
PRK10672 PRK10672
endolytic peptidoglycan transglycosylase RlpA;
230-351 1.16e-04

endolytic peptidoglycan transglycosylase RlpA;


Pssm-ID: 236733 [Multi-domain]  Cd Length: 361  Bit Score: 45.44  E-value: 1.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 230 TVLSQVPKaTSFAEP--PDYS-----PVTHNVPSPIGEIQPLS-------PQPSAPIASSPAIDMPpqsetisSPMPQTH 295
Cdd:PRK10672 182 TAGTTVAK-QSYALParPDLSggmgtPSVQPAPAPQGDVLPVSnstlkseDPTGAPVTSSGFLGAP-------TTLAPGV 253
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 296 VSGTPPPVKASFSSPtVSAPANVNTTSAPPVQTDI----VNTSSISDlENQVLQMEKALS 351
Cdd:PRK10672 254 LEGSEPTPTAPSSAP-ATAPAAAAPQAAATSSSASgnfvVQVGAVSD-QQRAQQWQQSLS 311
PHA03247 PHA03247
large tegument protein UL36; Provisional
210-339 1.32e-04

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 46.08  E-value: 1.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  210 DHPRGPPFSSSQSIPVVPRAtvlsqvPKATSFAEPPdYSPVTHNVPSPIGEIQPL---------SPQPSAPIASSPAIDM 280
Cdd:PHA03247 2861 DVRRRPPSRSPAAKPAAPAR------PPVRRLARPA-VSRSTESFALPPDQPERPpqpqappppQPQPQPPPPPQPQPPP 2933
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 296317300  281 PPQSETISSPMPQTHVSG-------TPPPVKASFSSPTVSAPANVNTTSAPPVQTDIVNTSSISDL 339
Cdd:PHA03247 2934 PPPPRPQPPLAPTTDPAGagepsgaVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPPLTGH 2999
PLN02983 PLN02983
biotin carboxyl carrier protein of acetyl-CoA carboxylase
237-304 2.13e-04

biotin carboxyl carrier protein of acetyl-CoA carboxylase


Pssm-ID: 215533 [Multi-domain]  Cd Length: 274  Bit Score: 44.44  E-value: 2.13e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 296317300 237 KATSFAEPPDYSPVTHNVPSPIGEIQPLSPQPSAPIASSPAidmPPQSETISSPMPQTHVSGTPPPVK 304
Cdd:PLN02983 137 KKEALPQPPPPAPVVMMQPPPPHAMPPASPPAAQPAPSAPA---SSPPPTPASPPPAKAPKSSHPPLK 201
PLN03209 PLN03209
translocon at the inner envelope of chloroplast subunit 62; Provisional
215-337 4.16e-04

translocon at the inner envelope of chloroplast subunit 62; Provisional


Pssm-ID: 178748 [Multi-domain]  Cd Length: 576  Bit Score: 44.15  E-value: 4.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 215 PPFSSSQSIPVVPRATVLSQvPKATSFAEPPDYSPVTHNVPSPIGEIQPLSP--------QPSAPIASSPAIDMPPQSET 286
Cdd:PLN03209 390 PPSSSPASSKSVDAVAKPAE-PDVVPSPGSASNVPEVEPAQVEAKKTRPLSPyaryedlkPPTSPSPTAPTGVSPSVSST 468
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 296317300 287 ISSPMpqthVSGTPPPvkASFSSPTVSAPANVNTTSAPPVQTDIVNTSSIS 337
Cdd:PLN03209 469 SSVPA----VPDTAPA--TAATDAAAPPPANMRPLSPYAVYDDLKPPTSPS 513
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
203-335 1.24e-03

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 42.85  E-value: 1.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300  203 DPIVCLADHPRGPPFSSSQSIPVVPRATVLSQVPKATSFAEPPDYSPVTHNVPSPIG-EIQPLSPQPSAPIASSPAIDM- 280
Cdd:PHA03307   62 CDRFEPPTGPPPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPDPPPpTPPPASPPPSPAPDLSEMLRPv 141
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 296317300  281 -----PPQSETISSPMPQTHV-SGTPPPVKASFSSPTVSAPAnvnTTSAPPVQTDIVNTSS 335
Cdd:PHA03307  142 gspgpPPAASPPAAGASPAAVaSDAASSRQAALPLSSPEETA---RAPSSPPAEPPPSTPP 199
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
656-853 1.61e-03

vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Vasoactive intestinal peptide (VIP) receptor 2 is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. VIP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320652 [Multi-domain]  Cd Length: 269  Bit Score: 41.33  E-value: 1.61e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTyiRKYILKFCIVGWGVPAVVVT--IILTISPDNYGlgsygkfpn 733
Cdd:cd15986   79 CKVSLVILQYCIMANFYWLLVEGLYLHTLLVVIFSE--NRHFIVYLLIGWGIPTVFIIawIVARIYLEDTG--------- 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 734 gspddfCW-INNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDL-RSIAGLTFLLGITWG-F 810
Cdd:cd15986  148 ------CWdTNDHSVPWWVIRIPIIISIILNFILFISIIRILLQKLRSPDVGGNDQSQYKRLaKSTLLLIPLFGVHYIvF 221
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 296317300 811 AFFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENV----RKQWR 853
Cdd:cd15986  222 VYFPDSSSSNYQIFFELCLGSFQGLVVAILYCFLNSEVqgelKRKWR 268
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
644-789 1.61e-03

class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 5 and 8 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, as well as their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320163  Cd Length: 307  Bit Score: 41.49  E-value: 1.61e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 644 DSWIALYKMQG--LCISVAVFLHYFLLVSFTWMGLEAFHMYLAL-VKVFNTYIRKYILKFCIVGWGVPAV-VVTIILTIS 719
Cdd:cd15035   75 DGGIIRYATTGpaLCTVVFLLTYFFGMASSIWWVILSLTWFLAAgLKWGNEAISSYSQYFHLVAWLIPAVqTIAILALSA 154
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296317300 720 PDnyglgsygkfpnGSP-DDFCWI--NNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKT 789
Cdd:cd15035  155 VD------------GDPiSGICYVgnQNLNNLRGFVLAPLVVYLILGTSFLLAGFVSLFRIRNVIKQQGGDKT 215
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
656-831 2.36e-03

class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor superfamily; The class F G protein-coupled receptors includes the frizzled (FZD) family of seven-transmembrane proteins consisting of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. Also included in the class F family is the closely related smoothened (SMO), which is a transmembrane G protein-coupled receptor that acts as the transducer of the hedgehog (HH) signaling pathway. SMO is activated by the hedgehog (HH) family of proteins acting on the 12-transmembrane domain receptor patched (PTCH), which constitutively inhibits SMO. Thus, in the absence of HH proteins, PTCH inhibits SMO signaling. On the other hand, binding of HH to the PTCH receptor activates its internalization and degradation, thereby releasing the PTCH inhibition of SMO. This allows SMO to trigger intracellular signaling and the subsequent activation of the Gli family of zinc finger transcriptional factors and induction of HH target gene expression (PTCH, Gli1, cyclin, Bcl-2, etc). The WNT and HH signaling pathways play critical roles in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320089  Cd Length: 314  Bit Score: 41.15  E-value: 2.36e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 656 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNT-YIRKYILKFCIVGWGVPAVVVTIILT---ISPDNY-GLgsygk 730
Cdd:cd13951   94 CAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSSeAIEKKSSYFHLVAWGLPAVLTIAVLVlrkVDGDELtGI----- 168
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296317300 731 fpngspddfCWINNNAVFYIT--VVGYFCViFLLNVSMFIVV-LVQLCRIKKKKQlGAQRKTSIQDLRSIagltfLLGIt 807
Cdd:cd13951  169 ---------CFVGNQNLDALRgfVLAPLFL-YLILGTVFLLCgFLSLFRIRSILS-NDGKKTDKLEKLML-----RIGI- 231
                        170       180
                 ....*....|....*....|....*
gi 296317300 808 wgFAFFAWGPVNVTF-MYLFAIFNT 831
Cdd:cd13951  232 --FAVLYTLPALIVIaCYFYEYANR 254
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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